Ignet

Gene Information

Gene symbol: TIPARP

Gene name: TCDD-inducible poly(ADP-ribose) polymerase

HGNC ID: 23696

Synonyms: DKFZP434J214, DKFZp686N0351, DDF1, PARP7, PARP-7, PARP-1, pART14, RM1

Related Genes

#	Gene Symbol	Number of hits
1	AIFM1	1 hits
2	ALB	1 hits
3	BRCA1	1 hits
4	BRCA2	1 hits
5	CAGE1	1 hits
6	CASP3	1 hits
7	CAT	1 hits
8	CD40	1 hits
9	COL1A1	1 hits
10	COX8A	1 hits
11	CTGF	1 hits
12	CXCL12	1 hits
13	CYBA	1 hits
14	FOS	1 hits
15	FOXO1	1 hits
16	GAPDH	1 hits
17	GCG	1 hits
18	GLP1R	1 hits
19	GORASP1	1 hits
20	GSTA1	1 hits
21	GSTCD	1 hits
22	INDO	1 hits
23	INS	1 hits
24	ITGAL	1 hits
25	JTB	1 hits
26	MAGED2	1 hits
27	MS	1 hits
28	NFKB1	1 hits
29	NOS2A	1 hits
30	NOS3	1 hits
31	NOX5	1 hits
32	PARG	1 hits
33	PARP1	1 hits
34	PARP10	1 hits
35	PARP2	1 hits
36	PARP3	1 hits
37	PARP4	1 hits
38	PRKDC	1 hits
39	PTGS2	1 hits
40	REG1A	1 hits
41	SIRT1	1 hits
42	SLC2A2	1 hits
43	SOD1	1 hits
44	SP1	1 hits
45	TGFA	1 hits
46	TNF	1 hits
47	TOP1	1 hits
48	TP53	1 hits
49	XRCC5	1 hits
50	YY1	1 hits

Related Sentences

#	PMID	Sentence
1	10856830	Poly (ADP-ribose) polymerase (113 kDa; PARP-1) is a constitutive factor of the DNA damage surveillance network developed by the eukaryotic cell to cope with the numerous environmental and endogenous genotoxic agents.
2	10856830	The generation, by homologous recombination, of three independent deficient mouse models have confirmed the caretaker function of PARP-1 in mammalian cells under genotoxic stress.
3	10856830	Unexpectedly, the knockout strategy has revealed the instrumental role of PARP-1 in cell death after ischemia-reperfusion injury and in various inflammation process.
4	10856830	Moreover, the residual PARP activity found in PARP-1 deficient cells has been recently attributed to a novel DNA damage-dependent poly ADP-ribose polymerase (62 kDa; PARP-2), another member of the expanding PARP family that, on the whole, appears to be involved in the genome protection.
5	10856830	Poly (ADP-ribose) polymerase (113 kDa; PARP-1) is a constitutive factor of the DNA damage surveillance network developed by the eukaryotic cell to cope with the numerous environmental and endogenous genotoxic agents.
6	10856830	The generation, by homologous recombination, of three independent deficient mouse models have confirmed the caretaker function of PARP-1 in mammalian cells under genotoxic stress.
7	10856830	Unexpectedly, the knockout strategy has revealed the instrumental role of PARP-1 in cell death after ischemia-reperfusion injury and in various inflammation process.
8	10856830	Moreover, the residual PARP activity found in PARP-1 deficient cells has been recently attributed to a novel DNA damage-dependent poly ADP-ribose polymerase (62 kDa; PARP-2), another member of the expanding PARP family that, on the whole, appears to be involved in the genome protection.
9	10856830	Poly (ADP-ribose) polymerase (113 kDa; PARP-1) is a constitutive factor of the DNA damage surveillance network developed by the eukaryotic cell to cope with the numerous environmental and endogenous genotoxic agents.
10	10856830	The generation, by homologous recombination, of three independent deficient mouse models have confirmed the caretaker function of PARP-1 in mammalian cells under genotoxic stress.
11	10856830	Unexpectedly, the knockout strategy has revealed the instrumental role of PARP-1 in cell death after ischemia-reperfusion injury and in various inflammation process.
12	10856830	Moreover, the residual PARP activity found in PARP-1 deficient cells has been recently attributed to a novel DNA damage-dependent poly ADP-ribose polymerase (62 kDa; PARP-2), another member of the expanding PARP family that, on the whole, appears to be involved in the genome protection.
13	10856830	Poly (ADP-ribose) polymerase (113 kDa; PARP-1) is a constitutive factor of the DNA damage surveillance network developed by the eukaryotic cell to cope with the numerous environmental and endogenous genotoxic agents.
14	10856830	The generation, by homologous recombination, of three independent deficient mouse models have confirmed the caretaker function of PARP-1 in mammalian cells under genotoxic stress.
15	10856830	Unexpectedly, the knockout strategy has revealed the instrumental role of PARP-1 in cell death after ischemia-reperfusion injury and in various inflammation process.
16	10856830	Moreover, the residual PARP activity found in PARP-1 deficient cells has been recently attributed to a novel DNA damage-dependent poly ADP-ribose polymerase (62 kDa; PARP-2), another member of the expanding PARP family that, on the whole, appears to be involved in the genome protection.
17	11590148	The enzymatic and DNA binding activity of PARP-1 are not required for NF-kappa B coactivator function.
18	11590148	Poly(ADP-ribose) polymerase 1 (PARP-1)-deficient mice are protected against septic shock, diabetes type I, stroke, and inflammation.
19	11590148	We report that primary cells from PARP-1(-/-) animals are impaired in kappa B-dependent transcriptional activation induced by different stimuli involved in inflammatory and genotoxic stress signaling.
20	11590148	PARP-1 was also required for p65-mediated transcriptional activation.
21	11590148	PARP-1 enzymatic inhibitors did not inhibit the transcriptional activation of a kappa B-dependent reporter gene in wild type cells.
22	11590148	Remarkably, neither the enzymatic activity nor the DNA binding activity of PARP-1 was required for kappa B-dependent transcriptional activation in PARP-1(-/-) cells complemented with different PARP-1 mutants.
23	11590148	However, PARP-1 interacted in vitro directly with both subunits of NF-kappa B (p50 and p65), and mapping of the interaction domains revealed that both subunits bind to different PARP-1 domains.
24	11590148	Furthermore, a PARP-1 mutant lacking the enzymatic and DNA binding activity interacted comparably to the wild type PARP-1 with p65 or p50.
25	11590148	Finally, we showed that PARP-1 is activating the natural inducible nitric-oxide synthase and P-selectin promoter in a kappa B-dependent manner upon stimulation of the cells with inflammatory stimuli or cotransfection of p65.
26	11590148	Our results provide evidence that neither the DNA binding nor the enzymatic activity of PARP-1 but its direct protein-protein interaction with both subunits of NF-kappa B is required for its coactivator function, thus expanding the role of PARP-1 as an essential and novel classical transcriptional coactivator for kappa B-dependent gene expression in vivo.
27	11590148	The enzymatic and DNA binding activity of PARP-1 are not required for NF-kappa B coactivator function.
28	11590148	Poly(ADP-ribose) polymerase 1 (PARP-1)-deficient mice are protected against septic shock, diabetes type I, stroke, and inflammation.
29	11590148	We report that primary cells from PARP-1(-/-) animals are impaired in kappa B-dependent transcriptional activation induced by different stimuli involved in inflammatory and genotoxic stress signaling.
30	11590148	PARP-1 was also required for p65-mediated transcriptional activation.
31	11590148	PARP-1 enzymatic inhibitors did not inhibit the transcriptional activation of a kappa B-dependent reporter gene in wild type cells.
32	11590148	Remarkably, neither the enzymatic activity nor the DNA binding activity of PARP-1 was required for kappa B-dependent transcriptional activation in PARP-1(-/-) cells complemented with different PARP-1 mutants.
33	11590148	However, PARP-1 interacted in vitro directly with both subunits of NF-kappa B (p50 and p65), and mapping of the interaction domains revealed that both subunits bind to different PARP-1 domains.
34	11590148	Furthermore, a PARP-1 mutant lacking the enzymatic and DNA binding activity interacted comparably to the wild type PARP-1 with p65 or p50.
35	11590148	Finally, we showed that PARP-1 is activating the natural inducible nitric-oxide synthase and P-selectin promoter in a kappa B-dependent manner upon stimulation of the cells with inflammatory stimuli or cotransfection of p65.
36	11590148	Our results provide evidence that neither the DNA binding nor the enzymatic activity of PARP-1 but its direct protein-protein interaction with both subunits of NF-kappa B is required for its coactivator function, thus expanding the role of PARP-1 as an essential and novel classical transcriptional coactivator for kappa B-dependent gene expression in vivo.
37	11590148	The enzymatic and DNA binding activity of PARP-1 are not required for NF-kappa B coactivator function.
38	11590148	Poly(ADP-ribose) polymerase 1 (PARP-1)-deficient mice are protected against septic shock, diabetes type I, stroke, and inflammation.
39	11590148	We report that primary cells from PARP-1(-/-) animals are impaired in kappa B-dependent transcriptional activation induced by different stimuli involved in inflammatory and genotoxic stress signaling.
40	11590148	PARP-1 was also required for p65-mediated transcriptional activation.
41	11590148	PARP-1 enzymatic inhibitors did not inhibit the transcriptional activation of a kappa B-dependent reporter gene in wild type cells.
42	11590148	Remarkably, neither the enzymatic activity nor the DNA binding activity of PARP-1 was required for kappa B-dependent transcriptional activation in PARP-1(-/-) cells complemented with different PARP-1 mutants.
43	11590148	However, PARP-1 interacted in vitro directly with both subunits of NF-kappa B (p50 and p65), and mapping of the interaction domains revealed that both subunits bind to different PARP-1 domains.
44	11590148	Furthermore, a PARP-1 mutant lacking the enzymatic and DNA binding activity interacted comparably to the wild type PARP-1 with p65 or p50.
45	11590148	Finally, we showed that PARP-1 is activating the natural inducible nitric-oxide synthase and P-selectin promoter in a kappa B-dependent manner upon stimulation of the cells with inflammatory stimuli or cotransfection of p65.
46	11590148	Our results provide evidence that neither the DNA binding nor the enzymatic activity of PARP-1 but its direct protein-protein interaction with both subunits of NF-kappa B is required for its coactivator function, thus expanding the role of PARP-1 as an essential and novel classical transcriptional coactivator for kappa B-dependent gene expression in vivo.
47	11590148	The enzymatic and DNA binding activity of PARP-1 are not required for NF-kappa B coactivator function.
48	11590148	Poly(ADP-ribose) polymerase 1 (PARP-1)-deficient mice are protected against septic shock, diabetes type I, stroke, and inflammation.
49	11590148	We report that primary cells from PARP-1(-/-) animals are impaired in kappa B-dependent transcriptional activation induced by different stimuli involved in inflammatory and genotoxic stress signaling.
50	11590148	PARP-1 was also required for p65-mediated transcriptional activation.
51	11590148	PARP-1 enzymatic inhibitors did not inhibit the transcriptional activation of a kappa B-dependent reporter gene in wild type cells.
52	11590148	Remarkably, neither the enzymatic activity nor the DNA binding activity of PARP-1 was required for kappa B-dependent transcriptional activation in PARP-1(-/-) cells complemented with different PARP-1 mutants.
53	11590148	However, PARP-1 interacted in vitro directly with both subunits of NF-kappa B (p50 and p65), and mapping of the interaction domains revealed that both subunits bind to different PARP-1 domains.
54	11590148	Furthermore, a PARP-1 mutant lacking the enzymatic and DNA binding activity interacted comparably to the wild type PARP-1 with p65 or p50.
55	11590148	Finally, we showed that PARP-1 is activating the natural inducible nitric-oxide synthase and P-selectin promoter in a kappa B-dependent manner upon stimulation of the cells with inflammatory stimuli or cotransfection of p65.
56	11590148	Our results provide evidence that neither the DNA binding nor the enzymatic activity of PARP-1 but its direct protein-protein interaction with both subunits of NF-kappa B is required for its coactivator function, thus expanding the role of PARP-1 as an essential and novel classical transcriptional coactivator for kappa B-dependent gene expression in vivo.
57	11590148	The enzymatic and DNA binding activity of PARP-1 are not required for NF-kappa B coactivator function.
58	11590148	Poly(ADP-ribose) polymerase 1 (PARP-1)-deficient mice are protected against septic shock, diabetes type I, stroke, and inflammation.
59	11590148	We report that primary cells from PARP-1(-/-) animals are impaired in kappa B-dependent transcriptional activation induced by different stimuli involved in inflammatory and genotoxic stress signaling.
60	11590148	PARP-1 was also required for p65-mediated transcriptional activation.
61	11590148	PARP-1 enzymatic inhibitors did not inhibit the transcriptional activation of a kappa B-dependent reporter gene in wild type cells.
62	11590148	Remarkably, neither the enzymatic activity nor the DNA binding activity of PARP-1 was required for kappa B-dependent transcriptional activation in PARP-1(-/-) cells complemented with different PARP-1 mutants.
63	11590148	However, PARP-1 interacted in vitro directly with both subunits of NF-kappa B (p50 and p65), and mapping of the interaction domains revealed that both subunits bind to different PARP-1 domains.
64	11590148	Furthermore, a PARP-1 mutant lacking the enzymatic and DNA binding activity interacted comparably to the wild type PARP-1 with p65 or p50.
65	11590148	Finally, we showed that PARP-1 is activating the natural inducible nitric-oxide synthase and P-selectin promoter in a kappa B-dependent manner upon stimulation of the cells with inflammatory stimuli or cotransfection of p65.
66	11590148	Our results provide evidence that neither the DNA binding nor the enzymatic activity of PARP-1 but its direct protein-protein interaction with both subunits of NF-kappa B is required for its coactivator function, thus expanding the role of PARP-1 as an essential and novel classical transcriptional coactivator for kappa B-dependent gene expression in vivo.
67	11590148	The enzymatic and DNA binding activity of PARP-1 are not required for NF-kappa B coactivator function.
68	11590148	Poly(ADP-ribose) polymerase 1 (PARP-1)-deficient mice are protected against septic shock, diabetes type I, stroke, and inflammation.
69	11590148	We report that primary cells from PARP-1(-/-) animals are impaired in kappa B-dependent transcriptional activation induced by different stimuli involved in inflammatory and genotoxic stress signaling.
70	11590148	PARP-1 was also required for p65-mediated transcriptional activation.
71	11590148	PARP-1 enzymatic inhibitors did not inhibit the transcriptional activation of a kappa B-dependent reporter gene in wild type cells.
72	11590148	Remarkably, neither the enzymatic activity nor the DNA binding activity of PARP-1 was required for kappa B-dependent transcriptional activation in PARP-1(-/-) cells complemented with different PARP-1 mutants.
73	11590148	However, PARP-1 interacted in vitro directly with both subunits of NF-kappa B (p50 and p65), and mapping of the interaction domains revealed that both subunits bind to different PARP-1 domains.
74	11590148	Furthermore, a PARP-1 mutant lacking the enzymatic and DNA binding activity interacted comparably to the wild type PARP-1 with p65 or p50.
75	11590148	Finally, we showed that PARP-1 is activating the natural inducible nitric-oxide synthase and P-selectin promoter in a kappa B-dependent manner upon stimulation of the cells with inflammatory stimuli or cotransfection of p65.
76	11590148	Our results provide evidence that neither the DNA binding nor the enzymatic activity of PARP-1 but its direct protein-protein interaction with both subunits of NF-kappa B is required for its coactivator function, thus expanding the role of PARP-1 as an essential and novel classical transcriptional coactivator for kappa B-dependent gene expression in vivo.
77	11590148	The enzymatic and DNA binding activity of PARP-1 are not required for NF-kappa B coactivator function.
78	11590148	Poly(ADP-ribose) polymerase 1 (PARP-1)-deficient mice are protected against septic shock, diabetes type I, stroke, and inflammation.
79	11590148	We report that primary cells from PARP-1(-/-) animals are impaired in kappa B-dependent transcriptional activation induced by different stimuli involved in inflammatory and genotoxic stress signaling.
80	11590148	PARP-1 was also required for p65-mediated transcriptional activation.
81	11590148	PARP-1 enzymatic inhibitors did not inhibit the transcriptional activation of a kappa B-dependent reporter gene in wild type cells.
82	11590148	Remarkably, neither the enzymatic activity nor the DNA binding activity of PARP-1 was required for kappa B-dependent transcriptional activation in PARP-1(-/-) cells complemented with different PARP-1 mutants.
83	11590148	However, PARP-1 interacted in vitro directly with both subunits of NF-kappa B (p50 and p65), and mapping of the interaction domains revealed that both subunits bind to different PARP-1 domains.
84	11590148	Furthermore, a PARP-1 mutant lacking the enzymatic and DNA binding activity interacted comparably to the wild type PARP-1 with p65 or p50.
85	11590148	Finally, we showed that PARP-1 is activating the natural inducible nitric-oxide synthase and P-selectin promoter in a kappa B-dependent manner upon stimulation of the cells with inflammatory stimuli or cotransfection of p65.
86	11590148	Our results provide evidence that neither the DNA binding nor the enzymatic activity of PARP-1 but its direct protein-protein interaction with both subunits of NF-kappa B is required for its coactivator function, thus expanding the role of PARP-1 as an essential and novel classical transcriptional coactivator for kappa B-dependent gene expression in vivo.
87	11590148	The enzymatic and DNA binding activity of PARP-1 are not required for NF-kappa B coactivator function.
88	11590148	Poly(ADP-ribose) polymerase 1 (PARP-1)-deficient mice are protected against septic shock, diabetes type I, stroke, and inflammation.
89	11590148	We report that primary cells from PARP-1(-/-) animals are impaired in kappa B-dependent transcriptional activation induced by different stimuli involved in inflammatory and genotoxic stress signaling.
90	11590148	PARP-1 was also required for p65-mediated transcriptional activation.
91	11590148	PARP-1 enzymatic inhibitors did not inhibit the transcriptional activation of a kappa B-dependent reporter gene in wild type cells.
92	11590148	Remarkably, neither the enzymatic activity nor the DNA binding activity of PARP-1 was required for kappa B-dependent transcriptional activation in PARP-1(-/-) cells complemented with different PARP-1 mutants.
93	11590148	However, PARP-1 interacted in vitro directly with both subunits of NF-kappa B (p50 and p65), and mapping of the interaction domains revealed that both subunits bind to different PARP-1 domains.
94	11590148	Furthermore, a PARP-1 mutant lacking the enzymatic and DNA binding activity interacted comparably to the wild type PARP-1 with p65 or p50.
95	11590148	Finally, we showed that PARP-1 is activating the natural inducible nitric-oxide synthase and P-selectin promoter in a kappa B-dependent manner upon stimulation of the cells with inflammatory stimuli or cotransfection of p65.
96	11590148	Our results provide evidence that neither the DNA binding nor the enzymatic activity of PARP-1 but its direct protein-protein interaction with both subunits of NF-kappa B is required for its coactivator function, thus expanding the role of PARP-1 as an essential and novel classical transcriptional coactivator for kappa B-dependent gene expression in vivo.
97	11590148	The enzymatic and DNA binding activity of PARP-1 are not required for NF-kappa B coactivator function.
98	11590148	Poly(ADP-ribose) polymerase 1 (PARP-1)-deficient mice are protected against septic shock, diabetes type I, stroke, and inflammation.
99	11590148	We report that primary cells from PARP-1(-/-) animals are impaired in kappa B-dependent transcriptional activation induced by different stimuli involved in inflammatory and genotoxic stress signaling.
100	11590148	PARP-1 was also required for p65-mediated transcriptional activation.
101	11590148	PARP-1 enzymatic inhibitors did not inhibit the transcriptional activation of a kappa B-dependent reporter gene in wild type cells.
102	11590148	Remarkably, neither the enzymatic activity nor the DNA binding activity of PARP-1 was required for kappa B-dependent transcriptional activation in PARP-1(-/-) cells complemented with different PARP-1 mutants.
103	11590148	However, PARP-1 interacted in vitro directly with both subunits of NF-kappa B (p50 and p65), and mapping of the interaction domains revealed that both subunits bind to different PARP-1 domains.
104	11590148	Furthermore, a PARP-1 mutant lacking the enzymatic and DNA binding activity interacted comparably to the wild type PARP-1 with p65 or p50.
105	11590148	Finally, we showed that PARP-1 is activating the natural inducible nitric-oxide synthase and P-selectin promoter in a kappa B-dependent manner upon stimulation of the cells with inflammatory stimuli or cotransfection of p65.
106	11590148	Our results provide evidence that neither the DNA binding nor the enzymatic activity of PARP-1 but its direct protein-protein interaction with both subunits of NF-kappa B is required for its coactivator function, thus expanding the role of PARP-1 as an essential and novel classical transcriptional coactivator for kappa B-dependent gene expression in vivo.
107	11590148	The enzymatic and DNA binding activity of PARP-1 are not required for NF-kappa B coactivator function.
108	11590148	Poly(ADP-ribose) polymerase 1 (PARP-1)-deficient mice are protected against septic shock, diabetes type I, stroke, and inflammation.
109	11590148	We report that primary cells from PARP-1(-/-) animals are impaired in kappa B-dependent transcriptional activation induced by different stimuli involved in inflammatory and genotoxic stress signaling.
110	11590148	PARP-1 was also required for p65-mediated transcriptional activation.
111	11590148	PARP-1 enzymatic inhibitors did not inhibit the transcriptional activation of a kappa B-dependent reporter gene in wild type cells.
112	11590148	Remarkably, neither the enzymatic activity nor the DNA binding activity of PARP-1 was required for kappa B-dependent transcriptional activation in PARP-1(-/-) cells complemented with different PARP-1 mutants.
113	11590148	However, PARP-1 interacted in vitro directly with both subunits of NF-kappa B (p50 and p65), and mapping of the interaction domains revealed that both subunits bind to different PARP-1 domains.
114	11590148	Furthermore, a PARP-1 mutant lacking the enzymatic and DNA binding activity interacted comparably to the wild type PARP-1 with p65 or p50.
115	11590148	Finally, we showed that PARP-1 is activating the natural inducible nitric-oxide synthase and P-selectin promoter in a kappa B-dependent manner upon stimulation of the cells with inflammatory stimuli or cotransfection of p65.
116	11590148	Our results provide evidence that neither the DNA binding nor the enzymatic activity of PARP-1 but its direct protein-protein interaction with both subunits of NF-kappa B is required for its coactivator function, thus expanding the role of PARP-1 as an essential and novel classical transcriptional coactivator for kappa B-dependent gene expression in vivo.
117	11846617	PARP-1, the best characterized member of the PARP family, that presently includes six members, is an abundant nuclear enzyme implicated in cellular responses to DNA injury provoked by genotoxic stress (oxygen radicals, ionizing radiations and monofunctional alkylating agents).
118	11846617	Due to its involvement either in DNA repair or in cell death, PARP-1 is regarded as a double-edged regulator of cellular functions.
119	11846617	In fact, when the DNA damage is moderate, PARP-1 participates in the DNA repair process.
120	11846617	Conversely, in the case of massive DNA injury, elevated PARP-1 activation leads to rapid NAD(+)/ATP consumption and cell death by necrosis.
121	11846617	Excessive PARP-1 activity has been implicated in the pathogenesis of numerous clinical conditions such as stroke, myocardial infarction, shock, diabetes and neurodegenerative disorders.
122	11846617	PARP-1 could therefore be considered as a potential target for the development of pharmacological strategies to enhance the antitumor efficacy of radio- and chemotherapy or to treat a number of clinical conditions characterized by oxidative or NO-induced stress and consequent PARP-1 activation.
123	11846617	PARP-1, the best characterized member of the PARP family, that presently includes six members, is an abundant nuclear enzyme implicated in cellular responses to DNA injury provoked by genotoxic stress (oxygen radicals, ionizing radiations and monofunctional alkylating agents).
124	11846617	Due to its involvement either in DNA repair or in cell death, PARP-1 is regarded as a double-edged regulator of cellular functions.
125	11846617	In fact, when the DNA damage is moderate, PARP-1 participates in the DNA repair process.
126	11846617	Conversely, in the case of massive DNA injury, elevated PARP-1 activation leads to rapid NAD(+)/ATP consumption and cell death by necrosis.
127	11846617	Excessive PARP-1 activity has been implicated in the pathogenesis of numerous clinical conditions such as stroke, myocardial infarction, shock, diabetes and neurodegenerative disorders.
128	11846617	PARP-1 could therefore be considered as a potential target for the development of pharmacological strategies to enhance the antitumor efficacy of radio- and chemotherapy or to treat a number of clinical conditions characterized by oxidative or NO-induced stress and consequent PARP-1 activation.
129	11846617	PARP-1, the best characterized member of the PARP family, that presently includes six members, is an abundant nuclear enzyme implicated in cellular responses to DNA injury provoked by genotoxic stress (oxygen radicals, ionizing radiations and monofunctional alkylating agents).
130	11846617	Due to its involvement either in DNA repair or in cell death, PARP-1 is regarded as a double-edged regulator of cellular functions.
131	11846617	In fact, when the DNA damage is moderate, PARP-1 participates in the DNA repair process.
132	11846617	Conversely, in the case of massive DNA injury, elevated PARP-1 activation leads to rapid NAD(+)/ATP consumption and cell death by necrosis.
133	11846617	Excessive PARP-1 activity has been implicated in the pathogenesis of numerous clinical conditions such as stroke, myocardial infarction, shock, diabetes and neurodegenerative disorders.
134	11846617	PARP-1 could therefore be considered as a potential target for the development of pharmacological strategies to enhance the antitumor efficacy of radio- and chemotherapy or to treat a number of clinical conditions characterized by oxidative or NO-induced stress and consequent PARP-1 activation.
135	11846617	PARP-1, the best characterized member of the PARP family, that presently includes six members, is an abundant nuclear enzyme implicated in cellular responses to DNA injury provoked by genotoxic stress (oxygen radicals, ionizing radiations and monofunctional alkylating agents).
136	11846617	Due to its involvement either in DNA repair or in cell death, PARP-1 is regarded as a double-edged regulator of cellular functions.
137	11846617	In fact, when the DNA damage is moderate, PARP-1 participates in the DNA repair process.
138	11846617	Conversely, in the case of massive DNA injury, elevated PARP-1 activation leads to rapid NAD(+)/ATP consumption and cell death by necrosis.
139	11846617	Excessive PARP-1 activity has been implicated in the pathogenesis of numerous clinical conditions such as stroke, myocardial infarction, shock, diabetes and neurodegenerative disorders.
140	11846617	PARP-1 could therefore be considered as a potential target for the development of pharmacological strategies to enhance the antitumor efficacy of radio- and chemotherapy or to treat a number of clinical conditions characterized by oxidative or NO-induced stress and consequent PARP-1 activation.
141	11846617	PARP-1, the best characterized member of the PARP family, that presently includes six members, is an abundant nuclear enzyme implicated in cellular responses to DNA injury provoked by genotoxic stress (oxygen radicals, ionizing radiations and monofunctional alkylating agents).
142	11846617	Due to its involvement either in DNA repair or in cell death, PARP-1 is regarded as a double-edged regulator of cellular functions.
143	11846617	In fact, when the DNA damage is moderate, PARP-1 participates in the DNA repair process.
144	11846617	Conversely, in the case of massive DNA injury, elevated PARP-1 activation leads to rapid NAD(+)/ATP consumption and cell death by necrosis.
145	11846617	Excessive PARP-1 activity has been implicated in the pathogenesis of numerous clinical conditions such as stroke, myocardial infarction, shock, diabetes and neurodegenerative disorders.
146	11846617	PARP-1 could therefore be considered as a potential target for the development of pharmacological strategies to enhance the antitumor efficacy of radio- and chemotherapy or to treat a number of clinical conditions characterized by oxidative or NO-induced stress and consequent PARP-1 activation.
147	11846617	PARP-1, the best characterized member of the PARP family, that presently includes six members, is an abundant nuclear enzyme implicated in cellular responses to DNA injury provoked by genotoxic stress (oxygen radicals, ionizing radiations and monofunctional alkylating agents).
148	11846617	Due to its involvement either in DNA repair or in cell death, PARP-1 is regarded as a double-edged regulator of cellular functions.
149	11846617	In fact, when the DNA damage is moderate, PARP-1 participates in the DNA repair process.
150	11846617	Conversely, in the case of massive DNA injury, elevated PARP-1 activation leads to rapid NAD(+)/ATP consumption and cell death by necrosis.
151	11846617	Excessive PARP-1 activity has been implicated in the pathogenesis of numerous clinical conditions such as stroke, myocardial infarction, shock, diabetes and neurodegenerative disorders.
152	11846617	PARP-1 could therefore be considered as a potential target for the development of pharmacological strategies to enhance the antitumor efficacy of radio- and chemotherapy or to treat a number of clinical conditions characterized by oxidative or NO-induced stress and consequent PARP-1 activation.
153	11978644	Poly(ADP-ribose) polymerase-1 (PARP-1) is a nuclear enzyme that consumes NAD in response to DNA strand breaks.
154	11978644	Its excessive activation seems particularly deleterious to pancreatic beta-cells, as exemplified by the complete resistance of PARP-1-deficient mice to the toxic diabetes induced by streptozotocin.
155	11978644	Because of the possible implication of this enzyme in type 1 diabetes, many human trials using nicotinamide, an inhibitor of PARP-1, have been conducted either in patients recently diagnosed or in subjects highly predisposed to this disease.
156	11978644	To analyze the role of this enzyme in murine type 1 diabetes, we introgressed a disrupted PARP-1 allele onto the autoimmune diabetes-prone nonobese diabetic (NOD) mouse strain.
157	11978644	Surprisingly they were also highly sensitive to the diabetes induced by a single high dose of streptozotocin, standing in sharp contrast with C57BL/6 mice that bear the same inactivated PARP-1 allele.
158	11978644	Our results suggest that NOD mice are characterized not only by their immune dysfunction but also by a peculiarity of their islets leading to a PARP-1-independent mechanism of streptozotocin-induced beta-cell death.
159	11978644	Poly(ADP-ribose) polymerase-1 (PARP-1) is a nuclear enzyme that consumes NAD in response to DNA strand breaks.
160	11978644	Its excessive activation seems particularly deleterious to pancreatic beta-cells, as exemplified by the complete resistance of PARP-1-deficient mice to the toxic diabetes induced by streptozotocin.
161	11978644	Because of the possible implication of this enzyme in type 1 diabetes, many human trials using nicotinamide, an inhibitor of PARP-1, have been conducted either in patients recently diagnosed or in subjects highly predisposed to this disease.
162	11978644	To analyze the role of this enzyme in murine type 1 diabetes, we introgressed a disrupted PARP-1 allele onto the autoimmune diabetes-prone nonobese diabetic (NOD) mouse strain.
163	11978644	Surprisingly they were also highly sensitive to the diabetes induced by a single high dose of streptozotocin, standing in sharp contrast with C57BL/6 mice that bear the same inactivated PARP-1 allele.
164	11978644	Our results suggest that NOD mice are characterized not only by their immune dysfunction but also by a peculiarity of their islets leading to a PARP-1-independent mechanism of streptozotocin-induced beta-cell death.
165	11978644	Poly(ADP-ribose) polymerase-1 (PARP-1) is a nuclear enzyme that consumes NAD in response to DNA strand breaks.
166	11978644	Its excessive activation seems particularly deleterious to pancreatic beta-cells, as exemplified by the complete resistance of PARP-1-deficient mice to the toxic diabetes induced by streptozotocin.
167	11978644	Because of the possible implication of this enzyme in type 1 diabetes, many human trials using nicotinamide, an inhibitor of PARP-1, have been conducted either in patients recently diagnosed or in subjects highly predisposed to this disease.
168	11978644	To analyze the role of this enzyme in murine type 1 diabetes, we introgressed a disrupted PARP-1 allele onto the autoimmune diabetes-prone nonobese diabetic (NOD) mouse strain.
169	11978644	Surprisingly they were also highly sensitive to the diabetes induced by a single high dose of streptozotocin, standing in sharp contrast with C57BL/6 mice that bear the same inactivated PARP-1 allele.
170	11978644	Our results suggest that NOD mice are characterized not only by their immune dysfunction but also by a peculiarity of their islets leading to a PARP-1-independent mechanism of streptozotocin-induced beta-cell death.
171	11978644	Poly(ADP-ribose) polymerase-1 (PARP-1) is a nuclear enzyme that consumes NAD in response to DNA strand breaks.
172	11978644	Its excessive activation seems particularly deleterious to pancreatic beta-cells, as exemplified by the complete resistance of PARP-1-deficient mice to the toxic diabetes induced by streptozotocin.
173	11978644	Because of the possible implication of this enzyme in type 1 diabetes, many human trials using nicotinamide, an inhibitor of PARP-1, have been conducted either in patients recently diagnosed or in subjects highly predisposed to this disease.
174	11978644	To analyze the role of this enzyme in murine type 1 diabetes, we introgressed a disrupted PARP-1 allele onto the autoimmune diabetes-prone nonobese diabetic (NOD) mouse strain.
175	11978644	Surprisingly they were also highly sensitive to the diabetes induced by a single high dose of streptozotocin, standing in sharp contrast with C57BL/6 mice that bear the same inactivated PARP-1 allele.
176	11978644	Our results suggest that NOD mice are characterized not only by their immune dysfunction but also by a peculiarity of their islets leading to a PARP-1-independent mechanism of streptozotocin-induced beta-cell death.
177	11978644	Poly(ADP-ribose) polymerase-1 (PARP-1) is a nuclear enzyme that consumes NAD in response to DNA strand breaks.
178	11978644	Its excessive activation seems particularly deleterious to pancreatic beta-cells, as exemplified by the complete resistance of PARP-1-deficient mice to the toxic diabetes induced by streptozotocin.
179	11978644	Because of the possible implication of this enzyme in type 1 diabetes, many human trials using nicotinamide, an inhibitor of PARP-1, have been conducted either in patients recently diagnosed or in subjects highly predisposed to this disease.
180	11978644	To analyze the role of this enzyme in murine type 1 diabetes, we introgressed a disrupted PARP-1 allele onto the autoimmune diabetes-prone nonobese diabetic (NOD) mouse strain.
181	11978644	Surprisingly they were also highly sensitive to the diabetes induced by a single high dose of streptozotocin, standing in sharp contrast with C57BL/6 mice that bear the same inactivated PARP-1 allele.
182	11978644	Our results suggest that NOD mice are characterized not only by their immune dysfunction but also by a peculiarity of their islets leading to a PARP-1-independent mechanism of streptozotocin-induced beta-cell death.
183	11978644	Poly(ADP-ribose) polymerase-1 (PARP-1) is a nuclear enzyme that consumes NAD in response to DNA strand breaks.
184	11978644	Its excessive activation seems particularly deleterious to pancreatic beta-cells, as exemplified by the complete resistance of PARP-1-deficient mice to the toxic diabetes induced by streptozotocin.
185	11978644	Because of the possible implication of this enzyme in type 1 diabetes, many human trials using nicotinamide, an inhibitor of PARP-1, have been conducted either in patients recently diagnosed or in subjects highly predisposed to this disease.
186	11978644	To analyze the role of this enzyme in murine type 1 diabetes, we introgressed a disrupted PARP-1 allele onto the autoimmune diabetes-prone nonobese diabetic (NOD) mouse strain.
187	11978644	Surprisingly they were also highly sensitive to the diabetes induced by a single high dose of streptozotocin, standing in sharp contrast with C57BL/6 mice that bear the same inactivated PARP-1 allele.
188	11978644	Our results suggest that NOD mice are characterized not only by their immune dysfunction but also by a peculiarity of their islets leading to a PARP-1-independent mechanism of streptozotocin-induced beta-cell death.
189	12223530	Poly(ADP-ribose) polymerase-1 (PARP-1) is a member of the PARP enzyme family consisting of PARP-1 and several recently identified novel poly(ADP-ribosylating) enzymes.
190	12223530	PARP-1 is an abundant nuclear protein functioning as a DNA nick-sensor enzyme.
191	12223530	Of special interest is the enhancement by PARP of nuclear factor kappa B-mediated transcription, which plays a central role in the expression of inflammatory cytokines, chemokines, adhesion molecules, and inflammatory mediators.
192	12223530	Poly(ADP-ribose) polymerase-1 (PARP-1) is a member of the PARP enzyme family consisting of PARP-1 and several recently identified novel poly(ADP-ribosylating) enzymes.
193	12223530	PARP-1 is an abundant nuclear protein functioning as a DNA nick-sensor enzyme.
194	12223530	Of special interest is the enhancement by PARP of nuclear factor kappa B-mediated transcription, which plays a central role in the expression of inflammatory cytokines, chemokines, adhesion molecules, and inflammatory mediators.
195	12440774	The functional role of poly(ADP-ribose)polymerase 1 as novel coactivator of NF-kappaB in inflammatory disorders.
196	12440774	Mammalian poly(ADP-ribose)polymerase 1 (PARP-1) is an abundant nuclear chromatin-associated protein and belongs to a large family of enzymes that catalyzes the transfer of ADP-ribose units from its substrate beta-nicotinamide adenine dinucleotide (NAD+) covalently to itself and other nuclear chromatin-associated proteins.
197	12440774	PARP-1 knockout mice are protected against myocardial infarction, streptozotocin-induced diabetes, lipopolysaccharide-induced septic shock, and zymosan-induced multiple organ failure, indicating that PARP-1 is involved in the regulation of the pathogenesis of these disorders.
198	12440774	PARP-1 and nuclear factor kappa B (NF-kappaB) have both been suggested to play a crucial role in inflammatory disorders.
199	12440774	Recent reports have shown that PARP-1 can act as a coactivator of NF-kappaB.
200	12440774	The purpose of this review is to give a short overview of the current knowledge about PARP-1 and its functional and biochemical interactions with NF-kappaB.
201	12440774	A more precise role for PARP-1 in NF-kappaB-dependent gene regulation and cellular metabolism during development of pathophysiological processes is discussed.
202	12440774	The functional role of poly(ADP-ribose)polymerase 1 as novel coactivator of NF-kappaB in inflammatory disorders.
203	12440774	Mammalian poly(ADP-ribose)polymerase 1 (PARP-1) is an abundant nuclear chromatin-associated protein and belongs to a large family of enzymes that catalyzes the transfer of ADP-ribose units from its substrate beta-nicotinamide adenine dinucleotide (NAD+) covalently to itself and other nuclear chromatin-associated proteins.
204	12440774	PARP-1 knockout mice are protected against myocardial infarction, streptozotocin-induced diabetes, lipopolysaccharide-induced septic shock, and zymosan-induced multiple organ failure, indicating that PARP-1 is involved in the regulation of the pathogenesis of these disorders.
205	12440774	PARP-1 and nuclear factor kappa B (NF-kappaB) have both been suggested to play a crucial role in inflammatory disorders.
206	12440774	Recent reports have shown that PARP-1 can act as a coactivator of NF-kappaB.
207	12440774	The purpose of this review is to give a short overview of the current knowledge about PARP-1 and its functional and biochemical interactions with NF-kappaB.
208	12440774	A more precise role for PARP-1 in NF-kappaB-dependent gene regulation and cellular metabolism during development of pathophysiological processes is discussed.
209	12440774	The functional role of poly(ADP-ribose)polymerase 1 as novel coactivator of NF-kappaB in inflammatory disorders.
210	12440774	Mammalian poly(ADP-ribose)polymerase 1 (PARP-1) is an abundant nuclear chromatin-associated protein and belongs to a large family of enzymes that catalyzes the transfer of ADP-ribose units from its substrate beta-nicotinamide adenine dinucleotide (NAD+) covalently to itself and other nuclear chromatin-associated proteins.
211	12440774	PARP-1 knockout mice are protected against myocardial infarction, streptozotocin-induced diabetes, lipopolysaccharide-induced septic shock, and zymosan-induced multiple organ failure, indicating that PARP-1 is involved in the regulation of the pathogenesis of these disorders.
212	12440774	PARP-1 and nuclear factor kappa B (NF-kappaB) have both been suggested to play a crucial role in inflammatory disorders.
213	12440774	Recent reports have shown that PARP-1 can act as a coactivator of NF-kappaB.
214	12440774	The purpose of this review is to give a short overview of the current knowledge about PARP-1 and its functional and biochemical interactions with NF-kappaB.
215	12440774	A more precise role for PARP-1 in NF-kappaB-dependent gene regulation and cellular metabolism during development of pathophysiological processes is discussed.
216	12440774	The functional role of poly(ADP-ribose)polymerase 1 as novel coactivator of NF-kappaB in inflammatory disorders.
217	12440774	Mammalian poly(ADP-ribose)polymerase 1 (PARP-1) is an abundant nuclear chromatin-associated protein and belongs to a large family of enzymes that catalyzes the transfer of ADP-ribose units from its substrate beta-nicotinamide adenine dinucleotide (NAD+) covalently to itself and other nuclear chromatin-associated proteins.
218	12440774	PARP-1 knockout mice are protected against myocardial infarction, streptozotocin-induced diabetes, lipopolysaccharide-induced septic shock, and zymosan-induced multiple organ failure, indicating that PARP-1 is involved in the regulation of the pathogenesis of these disorders.
219	12440774	PARP-1 and nuclear factor kappa B (NF-kappaB) have both been suggested to play a crucial role in inflammatory disorders.
220	12440774	Recent reports have shown that PARP-1 can act as a coactivator of NF-kappaB.
221	12440774	The purpose of this review is to give a short overview of the current knowledge about PARP-1 and its functional and biochemical interactions with NF-kappaB.
222	12440774	A more precise role for PARP-1 in NF-kappaB-dependent gene regulation and cellular metabolism during development of pathophysiological processes is discussed.
223	12440774	The functional role of poly(ADP-ribose)polymerase 1 as novel coactivator of NF-kappaB in inflammatory disorders.
224	12440774	Mammalian poly(ADP-ribose)polymerase 1 (PARP-1) is an abundant nuclear chromatin-associated protein and belongs to a large family of enzymes that catalyzes the transfer of ADP-ribose units from its substrate beta-nicotinamide adenine dinucleotide (NAD+) covalently to itself and other nuclear chromatin-associated proteins.
225	12440774	PARP-1 knockout mice are protected against myocardial infarction, streptozotocin-induced diabetes, lipopolysaccharide-induced septic shock, and zymosan-induced multiple organ failure, indicating that PARP-1 is involved in the regulation of the pathogenesis of these disorders.
226	12440774	PARP-1 and nuclear factor kappa B (NF-kappaB) have both been suggested to play a crucial role in inflammatory disorders.
227	12440774	Recent reports have shown that PARP-1 can act as a coactivator of NF-kappaB.
228	12440774	The purpose of this review is to give a short overview of the current knowledge about PARP-1 and its functional and biochemical interactions with NF-kappaB.
229	12440774	A more precise role for PARP-1 in NF-kappaB-dependent gene regulation and cellular metabolism during development of pathophysiological processes is discussed.
230	12440774	The functional role of poly(ADP-ribose)polymerase 1 as novel coactivator of NF-kappaB in inflammatory disorders.
231	12440774	Mammalian poly(ADP-ribose)polymerase 1 (PARP-1) is an abundant nuclear chromatin-associated protein and belongs to a large family of enzymes that catalyzes the transfer of ADP-ribose units from its substrate beta-nicotinamide adenine dinucleotide (NAD+) covalently to itself and other nuclear chromatin-associated proteins.
232	12440774	PARP-1 knockout mice are protected against myocardial infarction, streptozotocin-induced diabetes, lipopolysaccharide-induced septic shock, and zymosan-induced multiple organ failure, indicating that PARP-1 is involved in the regulation of the pathogenesis of these disorders.
233	12440774	PARP-1 and nuclear factor kappa B (NF-kappaB) have both been suggested to play a crucial role in inflammatory disorders.
234	12440774	Recent reports have shown that PARP-1 can act as a coactivator of NF-kappaB.
235	12440774	The purpose of this review is to give a short overview of the current knowledge about PARP-1 and its functional and biochemical interactions with NF-kappaB.
236	12440774	A more precise role for PARP-1 in NF-kappaB-dependent gene regulation and cellular metabolism during development of pathophysiological processes is discussed.
237	12570705	Poly(ADP-ribose) polymerase-1 (PARP-1) is the principal member of the PARP enzyme family consisting of PARP-1 and several recently identified novel poly(ADP-ribosyl)ating enzymes.
238	12570705	PARP-1 functions as a DNA damage sensor and signalling molecule.
239	12570705	Poly(ADP-ribose) polymerase-1 (PARP-1) is the principal member of the PARP enzyme family consisting of PARP-1 and several recently identified novel poly(ADP-ribosyl)ating enzymes.
240	12570705	PARP-1 functions as a DNA damage sensor and signalling molecule.
241	12676457	A DNA nick sensor enzyme, poly(ADP-ribose) polymerase-1 (PARP-1) also becomes activated upon sensing DNA breakage.
242	12676457	Activated PARP-1 cleaves NAD(+) into nicotinamide and ADP-ribose and polymerizes the latter on nuclear acceptor proteins.
243	12676457	A DNA nick sensor enzyme, poly(ADP-ribose) polymerase-1 (PARP-1) also becomes activated upon sensing DNA breakage.
244	12676457	Activated PARP-1 cleaves NAD(+) into nicotinamide and ADP-ribose and polymerizes the latter on nuclear acceptor proteins.
245	12677203	Poly(ADP-ribose) polymerase-1 (PARP-1) is a member of the PARP enzyme family consisting of PARP-1 and a growing family of additional, novel poly(ADP-ribosylating) enzymes.
246	12677203	PARP-1 is one of the most abundant nuclear proteins, and it functions as a DNA nick sensor enzyme.
247	12677203	In addition to the direct cytotoxic pathway regulated by DNA injury and PARP activation, PARP also modulates the course of cardiovascular inflammation and injury by regulating the activation of NF-kappaB, and the expression of a number of proinflammatory genes.
248	12677203	Poly(ADP-ribose) polymerase-1 (PARP-1) is a member of the PARP enzyme family consisting of PARP-1 and a growing family of additional, novel poly(ADP-ribosylating) enzymes.
249	12677203	PARP-1 is one of the most abundant nuclear proteins, and it functions as a DNA nick sensor enzyme.
250	12677203	In addition to the direct cytotoxic pathway regulated by DNA injury and PARP activation, PARP also modulates the course of cardiovascular inflammation and injury by regulating the activation of NF-kappaB, and the expression of a number of proinflammatory genes.
251	12853316	Poly(ADP-ribose) polymerase-1 (PARP-1) is an abundant nuclear enzyme that is activated primarily by DNA damage.
252	12853316	Upon activation, the enzyme hydrolyzes NAD(+) to nicotinamide and transfers ADP ribose units to a variety of nuclear proteins, including histones and PARP-1 itself.
253	12853316	However, excessive activation of PARP-1 can lead to significant decrements in NAD(+), and ATP depletion, and cell death (suicide hypothesis).
254	12853316	In response to cellular damage by oxygen radicals or excitotoxicity, a rapid and strong activation of PARP-1 occurs in neurons.
255	12853316	Excessive PARP-1 activation is implicated in a variety of insults, including cerebral and cardiac ischemia, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinsonism, traumatic spinal cord injury, and streptozotocin-induced diabetes.
256	12853316	Recent evidence indicates that this microglial migration is strongly controlled in living brain tissue by expression of the integrin CD11a, which is regulated in turn by PARP-1, proposing that PARP-1 downregulation may, therefore, be a promising strategy in protecting neurons from this secondary damage, as well.
257	12853316	Studies demonstrating an important role for PARP-1 in the regulation of gene transcription have further increased the intricacy of poly(ADP-ribosyl)ation in the control of cell homeostasis and challenge the notion that energy collapse is the sole mechanism by which poly(ADP-ribose) formation contributes to cell death.
258	12853316	The hypothesis that PARPs might regulate cell fate as essential modulators of death and survival transcriptional programs is discussed with relation to nuclear factor kappaB and p53.
259	12853316	Poly(ADP-ribose) polymerase-1 (PARP-1) is an abundant nuclear enzyme that is activated primarily by DNA damage.
260	12853316	Upon activation, the enzyme hydrolyzes NAD(+) to nicotinamide and transfers ADP ribose units to a variety of nuclear proteins, including histones and PARP-1 itself.
261	12853316	However, excessive activation of PARP-1 can lead to significant decrements in NAD(+), and ATP depletion, and cell death (suicide hypothesis).
262	12853316	In response to cellular damage by oxygen radicals or excitotoxicity, a rapid and strong activation of PARP-1 occurs in neurons.
263	12853316	Excessive PARP-1 activation is implicated in a variety of insults, including cerebral and cardiac ischemia, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinsonism, traumatic spinal cord injury, and streptozotocin-induced diabetes.
264	12853316	Recent evidence indicates that this microglial migration is strongly controlled in living brain tissue by expression of the integrin CD11a, which is regulated in turn by PARP-1, proposing that PARP-1 downregulation may, therefore, be a promising strategy in protecting neurons from this secondary damage, as well.
265	12853316	Studies demonstrating an important role for PARP-1 in the regulation of gene transcription have further increased the intricacy of poly(ADP-ribosyl)ation in the control of cell homeostasis and challenge the notion that energy collapse is the sole mechanism by which poly(ADP-ribose) formation contributes to cell death.
266	12853316	The hypothesis that PARPs might regulate cell fate as essential modulators of death and survival transcriptional programs is discussed with relation to nuclear factor kappaB and p53.
267	12853316	Poly(ADP-ribose) polymerase-1 (PARP-1) is an abundant nuclear enzyme that is activated primarily by DNA damage.
268	12853316	Upon activation, the enzyme hydrolyzes NAD(+) to nicotinamide and transfers ADP ribose units to a variety of nuclear proteins, including histones and PARP-1 itself.
269	12853316	However, excessive activation of PARP-1 can lead to significant decrements in NAD(+), and ATP depletion, and cell death (suicide hypothesis).
270	12853316	In response to cellular damage by oxygen radicals or excitotoxicity, a rapid and strong activation of PARP-1 occurs in neurons.
271	12853316	Excessive PARP-1 activation is implicated in a variety of insults, including cerebral and cardiac ischemia, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinsonism, traumatic spinal cord injury, and streptozotocin-induced diabetes.
272	12853316	Recent evidence indicates that this microglial migration is strongly controlled in living brain tissue by expression of the integrin CD11a, which is regulated in turn by PARP-1, proposing that PARP-1 downregulation may, therefore, be a promising strategy in protecting neurons from this secondary damage, as well.
273	12853316	Studies demonstrating an important role for PARP-1 in the regulation of gene transcription have further increased the intricacy of poly(ADP-ribosyl)ation in the control of cell homeostasis and challenge the notion that energy collapse is the sole mechanism by which poly(ADP-ribose) formation contributes to cell death.
274	12853316	The hypothesis that PARPs might regulate cell fate as essential modulators of death and survival transcriptional programs is discussed with relation to nuclear factor kappaB and p53.
275	12853316	Poly(ADP-ribose) polymerase-1 (PARP-1) is an abundant nuclear enzyme that is activated primarily by DNA damage.
276	12853316	Upon activation, the enzyme hydrolyzes NAD(+) to nicotinamide and transfers ADP ribose units to a variety of nuclear proteins, including histones and PARP-1 itself.
277	12853316	However, excessive activation of PARP-1 can lead to significant decrements in NAD(+), and ATP depletion, and cell death (suicide hypothesis).
278	12853316	In response to cellular damage by oxygen radicals or excitotoxicity, a rapid and strong activation of PARP-1 occurs in neurons.
279	12853316	Excessive PARP-1 activation is implicated in a variety of insults, including cerebral and cardiac ischemia, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinsonism, traumatic spinal cord injury, and streptozotocin-induced diabetes.
280	12853316	Recent evidence indicates that this microglial migration is strongly controlled in living brain tissue by expression of the integrin CD11a, which is regulated in turn by PARP-1, proposing that PARP-1 downregulation may, therefore, be a promising strategy in protecting neurons from this secondary damage, as well.
281	12853316	Studies demonstrating an important role for PARP-1 in the regulation of gene transcription have further increased the intricacy of poly(ADP-ribosyl)ation in the control of cell homeostasis and challenge the notion that energy collapse is the sole mechanism by which poly(ADP-ribose) formation contributes to cell death.
282	12853316	The hypothesis that PARPs might regulate cell fate as essential modulators of death and survival transcriptional programs is discussed with relation to nuclear factor kappaB and p53.
283	12853316	Poly(ADP-ribose) polymerase-1 (PARP-1) is an abundant nuclear enzyme that is activated primarily by DNA damage.
284	12853316	Upon activation, the enzyme hydrolyzes NAD(+) to nicotinamide and transfers ADP ribose units to a variety of nuclear proteins, including histones and PARP-1 itself.
285	12853316	However, excessive activation of PARP-1 can lead to significant decrements in NAD(+), and ATP depletion, and cell death (suicide hypothesis).
286	12853316	In response to cellular damage by oxygen radicals or excitotoxicity, a rapid and strong activation of PARP-1 occurs in neurons.
287	12853316	Excessive PARP-1 activation is implicated in a variety of insults, including cerebral and cardiac ischemia, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinsonism, traumatic spinal cord injury, and streptozotocin-induced diabetes.
288	12853316	Recent evidence indicates that this microglial migration is strongly controlled in living brain tissue by expression of the integrin CD11a, which is regulated in turn by PARP-1, proposing that PARP-1 downregulation may, therefore, be a promising strategy in protecting neurons from this secondary damage, as well.
289	12853316	Studies demonstrating an important role for PARP-1 in the regulation of gene transcription have further increased the intricacy of poly(ADP-ribosyl)ation in the control of cell homeostasis and challenge the notion that energy collapse is the sole mechanism by which poly(ADP-ribose) formation contributes to cell death.
290	12853316	The hypothesis that PARPs might regulate cell fate as essential modulators of death and survival transcriptional programs is discussed with relation to nuclear factor kappaB and p53.
291	12853316	Poly(ADP-ribose) polymerase-1 (PARP-1) is an abundant nuclear enzyme that is activated primarily by DNA damage.
292	12853316	Upon activation, the enzyme hydrolyzes NAD(+) to nicotinamide and transfers ADP ribose units to a variety of nuclear proteins, including histones and PARP-1 itself.
293	12853316	However, excessive activation of PARP-1 can lead to significant decrements in NAD(+), and ATP depletion, and cell death (suicide hypothesis).
294	12853316	In response to cellular damage by oxygen radicals or excitotoxicity, a rapid and strong activation of PARP-1 occurs in neurons.
295	12853316	Excessive PARP-1 activation is implicated in a variety of insults, including cerebral and cardiac ischemia, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinsonism, traumatic spinal cord injury, and streptozotocin-induced diabetes.
296	12853316	Recent evidence indicates that this microglial migration is strongly controlled in living brain tissue by expression of the integrin CD11a, which is regulated in turn by PARP-1, proposing that PARP-1 downregulation may, therefore, be a promising strategy in protecting neurons from this secondary damage, as well.
297	12853316	Studies demonstrating an important role for PARP-1 in the regulation of gene transcription have further increased the intricacy of poly(ADP-ribosyl)ation in the control of cell homeostasis and challenge the notion that energy collapse is the sole mechanism by which poly(ADP-ribose) formation contributes to cell death.
298	12853316	The hypothesis that PARPs might regulate cell fate as essential modulators of death and survival transcriptional programs is discussed with relation to nuclear factor kappaB and p53.
299	12853316	Poly(ADP-ribose) polymerase-1 (PARP-1) is an abundant nuclear enzyme that is activated primarily by DNA damage.
300	12853316	Upon activation, the enzyme hydrolyzes NAD(+) to nicotinamide and transfers ADP ribose units to a variety of nuclear proteins, including histones and PARP-1 itself.
301	12853316	However, excessive activation of PARP-1 can lead to significant decrements in NAD(+), and ATP depletion, and cell death (suicide hypothesis).
302	12853316	In response to cellular damage by oxygen radicals or excitotoxicity, a rapid and strong activation of PARP-1 occurs in neurons.
303	12853316	Excessive PARP-1 activation is implicated in a variety of insults, including cerebral and cardiac ischemia, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinsonism, traumatic spinal cord injury, and streptozotocin-induced diabetes.
304	12853316	Recent evidence indicates that this microglial migration is strongly controlled in living brain tissue by expression of the integrin CD11a, which is regulated in turn by PARP-1, proposing that PARP-1 downregulation may, therefore, be a promising strategy in protecting neurons from this secondary damage, as well.
305	12853316	Studies demonstrating an important role for PARP-1 in the regulation of gene transcription have further increased the intricacy of poly(ADP-ribosyl)ation in the control of cell homeostasis and challenge the notion that energy collapse is the sole mechanism by which poly(ADP-ribose) formation contributes to cell death.
306	12853316	The hypothesis that PARPs might regulate cell fate as essential modulators of death and survival transcriptional programs is discussed with relation to nuclear factor kappaB and p53.
307	12901915	Design and synthesis of poly(ADP-ribose) polymerase-1 (PARP-1) inhibitors.
308	12901915	Part 4: biological evaluation of imidazobenzodiazepines as potent PARP-1 inhibitors for treatment of ischemic injuries.
309	12901915	A class of poly(ADP-ribose) polymerase (PARP-1) inhibitors, the imidazobenzodiazepines, are presented in this text.
310	12901915	Within this series, several compounds have excellent in vitro potency and our computational models accurately justify the structure-activity relationships (SARs) and highlight essential hydrogen bonding residues and hydrophobic pockets within the catalytic domain of PARP-1.
311	12901915	Design and synthesis of poly(ADP-ribose) polymerase-1 (PARP-1) inhibitors.
312	12901915	Part 4: biological evaluation of imidazobenzodiazepines as potent PARP-1 inhibitors for treatment of ischemic injuries.
313	12901915	A class of poly(ADP-ribose) polymerase (PARP-1) inhibitors, the imidazobenzodiazepines, are presented in this text.
314	12901915	Within this series, several compounds have excellent in vitro potency and our computational models accurately justify the structure-activity relationships (SARs) and highlight essential hydrogen bonding residues and hydrophobic pockets within the catalytic domain of PARP-1.
315	12901915	Design and synthesis of poly(ADP-ribose) polymerase-1 (PARP-1) inhibitors.
316	12901915	Part 4: biological evaluation of imidazobenzodiazepines as potent PARP-1 inhibitors for treatment of ischemic injuries.
317	12901915	A class of poly(ADP-ribose) polymerase (PARP-1) inhibitors, the imidazobenzodiazepines, are presented in this text.
318	12901915	Within this series, several compounds have excellent in vitro potency and our computational models accurately justify the structure-activity relationships (SARs) and highlight essential hydrogen bonding residues and hydrophobic pockets within the catalytic domain of PARP-1.
319	12901915	Design and synthesis of poly(ADP-ribose) polymerase-1 (PARP-1) inhibitors.
320	12901915	Part 4: biological evaluation of imidazobenzodiazepines as potent PARP-1 inhibitors for treatment of ischemic injuries.
321	12901915	A class of poly(ADP-ribose) polymerase (PARP-1) inhibitors, the imidazobenzodiazepines, are presented in this text.
322	12901915	Within this series, several compounds have excellent in vitro potency and our computational models accurately justify the structure-activity relationships (SARs) and highlight essential hydrogen bonding residues and hydrophobic pockets within the catalytic domain of PARP-1.
323	14523042	Inhibition of GAPDH activity by poly(ADP-ribose) polymerase activates three major pathways of hyperglycemic damage in endothelial cells.
324	14523042	Hyperglycemia-induced GAPDH inhibition was found to be a consequence of poly(ADP-ribosyl)ation of GAPDH by poly(ADP-ribose) polymerase (PARP), which was activated by DNA strand breaks produced by mitochondrial superoxide overproduction.
325	14523042	Both the hyperglycemia-induced decrease in activity of GAPDH and its poly(ADP-ribosyl)ation were prevented by overexpression of either uncoupling protein-1 (UCP-1) or manganese superoxide dismutase (MnSOD), which decrease hyperglycemia-induced superoxide.
326	14523042	Overexpression of UCP-1 or MnSOD also prevented hyperglycemia-induced DNA strand breaks and activation of PARP.
327	14523042	Elevated glucose increased poly(ADP-ribosyl)ation of GAPDH in WT aortae, but not in the aortae from PARP-1-deficient mice.
328	14529360	Poly(ADP-ribose) polymerase 1 (PARP-1) protects the genome by functioning in the DNA damage surveillance network.
329	14529360	In response to stresses that are toxic to the genome, PARP-1 activity increases substantially, an event that appears crucial for maintaining genomic integrity.
330	14529360	Massive PARP-1 activation, however, can deplete the cell of NAD(+) and ATP, ultimately leading to energy failure and cell death.
331	14529360	The discovery that cell death may be suppressed by PARP inhibitors or by deletion of the parp-1 gene has prompted a great deal of interest in the process of poly(ADP-ribosyl)ation.
332	14529360	Suppression of PARP-1 is capable of protecting against cerebral and cardiac ischemia, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonism, traumatic spinal cord injury, and streptozotocin-induced diabetes.
333	14529360	Microglial migration is strongly controlled in living brain tissue by expression of the integrin CD11a, which is regulated in turn by PARP-1, proposing that PARP-1 downregulation may therefore be a promising strategy in protecting neurons from this secondary damage, as well.
334	14529360	As PARP-1 is now recognised as playing a role also in the regulation of gene transcription, this further increases the intricacy of poly(ADP-ribosyl)ation in the control of cell homeostasis and challenges the notion that energy collapse is the sole mechanism by which poly(ADP-ribose) formation contributes to cell death.
335	14529360	PARP(s) might regulate cell fate as essential modulators of death and survival transcriptional programs with relation to NF-kappaB and p53, proposing that inhibitors of poly(ADP-ribosyl)ation could therefore prevent the deleterious consequences of neuroinflammation by reducing NF-kappaB activity.
336	14529360	Poly(ADP-ribose) polymerase 1 (PARP-1) protects the genome by functioning in the DNA damage surveillance network.
337	14529360	In response to stresses that are toxic to the genome, PARP-1 activity increases substantially, an event that appears crucial for maintaining genomic integrity.
338	14529360	Massive PARP-1 activation, however, can deplete the cell of NAD(+) and ATP, ultimately leading to energy failure and cell death.
339	14529360	The discovery that cell death may be suppressed by PARP inhibitors or by deletion of the parp-1 gene has prompted a great deal of interest in the process of poly(ADP-ribosyl)ation.
340	14529360	Suppression of PARP-1 is capable of protecting against cerebral and cardiac ischemia, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonism, traumatic spinal cord injury, and streptozotocin-induced diabetes.
341	14529360	Microglial migration is strongly controlled in living brain tissue by expression of the integrin CD11a, which is regulated in turn by PARP-1, proposing that PARP-1 downregulation may therefore be a promising strategy in protecting neurons from this secondary damage, as well.
342	14529360	As PARP-1 is now recognised as playing a role also in the regulation of gene transcription, this further increases the intricacy of poly(ADP-ribosyl)ation in the control of cell homeostasis and challenges the notion that energy collapse is the sole mechanism by which poly(ADP-ribose) formation contributes to cell death.
343	14529360	PARP(s) might regulate cell fate as essential modulators of death and survival transcriptional programs with relation to NF-kappaB and p53, proposing that inhibitors of poly(ADP-ribosyl)ation could therefore prevent the deleterious consequences of neuroinflammation by reducing NF-kappaB activity.
344	14529360	Poly(ADP-ribose) polymerase 1 (PARP-1) protects the genome by functioning in the DNA damage surveillance network.
345	14529360	In response to stresses that are toxic to the genome, PARP-1 activity increases substantially, an event that appears crucial for maintaining genomic integrity.
346	14529360	Massive PARP-1 activation, however, can deplete the cell of NAD(+) and ATP, ultimately leading to energy failure and cell death.
347	14529360	The discovery that cell death may be suppressed by PARP inhibitors or by deletion of the parp-1 gene has prompted a great deal of interest in the process of poly(ADP-ribosyl)ation.
348	14529360	Suppression of PARP-1 is capable of protecting against cerebral and cardiac ischemia, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonism, traumatic spinal cord injury, and streptozotocin-induced diabetes.
349	14529360	Microglial migration is strongly controlled in living brain tissue by expression of the integrin CD11a, which is regulated in turn by PARP-1, proposing that PARP-1 downregulation may therefore be a promising strategy in protecting neurons from this secondary damage, as well.
350	14529360	As PARP-1 is now recognised as playing a role also in the regulation of gene transcription, this further increases the intricacy of poly(ADP-ribosyl)ation in the control of cell homeostasis and challenges the notion that energy collapse is the sole mechanism by which poly(ADP-ribose) formation contributes to cell death.
351	14529360	PARP(s) might regulate cell fate as essential modulators of death and survival transcriptional programs with relation to NF-kappaB and p53, proposing that inhibitors of poly(ADP-ribosyl)ation could therefore prevent the deleterious consequences of neuroinflammation by reducing NF-kappaB activity.
352	14529360	Poly(ADP-ribose) polymerase 1 (PARP-1) protects the genome by functioning in the DNA damage surveillance network.
353	14529360	In response to stresses that are toxic to the genome, PARP-1 activity increases substantially, an event that appears crucial for maintaining genomic integrity.
354	14529360	Massive PARP-1 activation, however, can deplete the cell of NAD(+) and ATP, ultimately leading to energy failure and cell death.
355	14529360	The discovery that cell death may be suppressed by PARP inhibitors or by deletion of the parp-1 gene has prompted a great deal of interest in the process of poly(ADP-ribosyl)ation.
356	14529360	Suppression of PARP-1 is capable of protecting against cerebral and cardiac ischemia, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonism, traumatic spinal cord injury, and streptozotocin-induced diabetes.
357	14529360	Microglial migration is strongly controlled in living brain tissue by expression of the integrin CD11a, which is regulated in turn by PARP-1, proposing that PARP-1 downregulation may therefore be a promising strategy in protecting neurons from this secondary damage, as well.
358	14529360	As PARP-1 is now recognised as playing a role also in the regulation of gene transcription, this further increases the intricacy of poly(ADP-ribosyl)ation in the control of cell homeostasis and challenges the notion that energy collapse is the sole mechanism by which poly(ADP-ribose) formation contributes to cell death.
359	14529360	PARP(s) might regulate cell fate as essential modulators of death and survival transcriptional programs with relation to NF-kappaB and p53, proposing that inhibitors of poly(ADP-ribosyl)ation could therefore prevent the deleterious consequences of neuroinflammation by reducing NF-kappaB activity.
360	14529360	Poly(ADP-ribose) polymerase 1 (PARP-1) protects the genome by functioning in the DNA damage surveillance network.
361	14529360	In response to stresses that are toxic to the genome, PARP-1 activity increases substantially, an event that appears crucial for maintaining genomic integrity.
362	14529360	Massive PARP-1 activation, however, can deplete the cell of NAD(+) and ATP, ultimately leading to energy failure and cell death.
363	14529360	The discovery that cell death may be suppressed by PARP inhibitors or by deletion of the parp-1 gene has prompted a great deal of interest in the process of poly(ADP-ribosyl)ation.
364	14529360	Suppression of PARP-1 is capable of protecting against cerebral and cardiac ischemia, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonism, traumatic spinal cord injury, and streptozotocin-induced diabetes.
365	14529360	Microglial migration is strongly controlled in living brain tissue by expression of the integrin CD11a, which is regulated in turn by PARP-1, proposing that PARP-1 downregulation may therefore be a promising strategy in protecting neurons from this secondary damage, as well.
366	14529360	As PARP-1 is now recognised as playing a role also in the regulation of gene transcription, this further increases the intricacy of poly(ADP-ribosyl)ation in the control of cell homeostasis and challenges the notion that energy collapse is the sole mechanism by which poly(ADP-ribose) formation contributes to cell death.
367	14529360	PARP(s) might regulate cell fate as essential modulators of death and survival transcriptional programs with relation to NF-kappaB and p53, proposing that inhibitors of poly(ADP-ribosyl)ation could therefore prevent the deleterious consequences of neuroinflammation by reducing NF-kappaB activity.
368	14529360	Poly(ADP-ribose) polymerase 1 (PARP-1) protects the genome by functioning in the DNA damage surveillance network.
369	14529360	In response to stresses that are toxic to the genome, PARP-1 activity increases substantially, an event that appears crucial for maintaining genomic integrity.
370	14529360	Massive PARP-1 activation, however, can deplete the cell of NAD(+) and ATP, ultimately leading to energy failure and cell death.
371	14529360	The discovery that cell death may be suppressed by PARP inhibitors or by deletion of the parp-1 gene has prompted a great deal of interest in the process of poly(ADP-ribosyl)ation.
372	14529360	Suppression of PARP-1 is capable of protecting against cerebral and cardiac ischemia, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonism, traumatic spinal cord injury, and streptozotocin-induced diabetes.
373	14529360	Microglial migration is strongly controlled in living brain tissue by expression of the integrin CD11a, which is regulated in turn by PARP-1, proposing that PARP-1 downregulation may therefore be a promising strategy in protecting neurons from this secondary damage, as well.
374	14529360	As PARP-1 is now recognised as playing a role also in the regulation of gene transcription, this further increases the intricacy of poly(ADP-ribosyl)ation in the control of cell homeostasis and challenges the notion that energy collapse is the sole mechanism by which poly(ADP-ribose) formation contributes to cell death.
375	14529360	PARP(s) might regulate cell fate as essential modulators of death and survival transcriptional programs with relation to NF-kappaB and p53, proposing that inhibitors of poly(ADP-ribosyl)ation could therefore prevent the deleterious consequences of neuroinflammation by reducing NF-kappaB activity.
376	14529360	Poly(ADP-ribose) polymerase 1 (PARP-1) protects the genome by functioning in the DNA damage surveillance network.
377	14529360	In response to stresses that are toxic to the genome, PARP-1 activity increases substantially, an event that appears crucial for maintaining genomic integrity.
378	14529360	Massive PARP-1 activation, however, can deplete the cell of NAD(+) and ATP, ultimately leading to energy failure and cell death.
379	14529360	The discovery that cell death may be suppressed by PARP inhibitors or by deletion of the parp-1 gene has prompted a great deal of interest in the process of poly(ADP-ribosyl)ation.
380	14529360	Suppression of PARP-1 is capable of protecting against cerebral and cardiac ischemia, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonism, traumatic spinal cord injury, and streptozotocin-induced diabetes.
381	14529360	Microglial migration is strongly controlled in living brain tissue by expression of the integrin CD11a, which is regulated in turn by PARP-1, proposing that PARP-1 downregulation may therefore be a promising strategy in protecting neurons from this secondary damage, as well.
382	14529360	As PARP-1 is now recognised as playing a role also in the regulation of gene transcription, this further increases the intricacy of poly(ADP-ribosyl)ation in the control of cell homeostasis and challenges the notion that energy collapse is the sole mechanism by which poly(ADP-ribose) formation contributes to cell death.
383	14529360	PARP(s) might regulate cell fate as essential modulators of death and survival transcriptional programs with relation to NF-kappaB and p53, proposing that inhibitors of poly(ADP-ribosyl)ation could therefore prevent the deleterious consequences of neuroinflammation by reducing NF-kappaB activity.
384	15054118	Poly(ADP-ribose) polymerase contributes to the development of myocardial infarction in diabetic rats and regulates the nuclear translocation of apoptosis-inducing factor.
385	15054118	Activation of the nuclear enzyme poly(ADP-ribose) polymerase (PARP)-1 by oxidant-mediated DNA damage is an important pathway of cell dysfunction and tissue injury during myocardial infarction.
386	15054118	In addition, there was a significant degree of mitochondrial-to-nuclear translocation of the cell death effector apoptosis-inducing factor (AIF) in myocardial infarction, which was blocked by pharmacological inhibition of PARP.
387	15054118	The role of PARP in regulating AIF translocation in myocytes also was confirmed in an isolated perfused heart preparation.
388	15054118	Overall, the current results demonstrate the importance of the PARP pathway in diabetic rats subjected to myocardial infarction and demonstrate the role of PARP in regulating AIF translocation in MI/R.
389	15077172	Crosstalk between PARP-1 and NF-kappaB modulates the promotion of skin neoplasia.
390	15077172	Poly (ADP-ribose) polymerase-1 (PARP-1)-deficient mice are protected against septic shock, type I diabetes, stroke and inflammation.
391	15077172	Here, we report that PARP-1-deficient mice display a strikingly reduced susceptibility to skin carcinogenesis.
392	15077172	In parp-1(-/-) mice, development of papilloma-like premalignant lesions induced with DMBA and TPA, is strongly delayed and the final number of tumor-bearing mice and total tumor number were significantly reduced.
393	15077172	In addition, epidermis of parp-1(-/-) mice did not show increased proliferation rates after treatment with carcinogen.
394	15077172	In the absence of PARP-1, NF-kappaB activation and induction kappaB-target genes did not take place during the promotion of tumor development.
395	15077172	These results suggest that PARP-1 abolition impairs the promotion of skin carcinogenesis interfering with the activation of NF-kappaB and might have an important implication in targeting PARP-1 as a new antineoplastic therapeutic approach.
396	15077172	Crosstalk between PARP-1 and NF-kappaB modulates the promotion of skin neoplasia.
397	15077172	Poly (ADP-ribose) polymerase-1 (PARP-1)-deficient mice are protected against septic shock, type I diabetes, stroke and inflammation.
398	15077172	Here, we report that PARP-1-deficient mice display a strikingly reduced susceptibility to skin carcinogenesis.
399	15077172	In parp-1(-/-) mice, development of papilloma-like premalignant lesions induced with DMBA and TPA, is strongly delayed and the final number of tumor-bearing mice and total tumor number were significantly reduced.
400	15077172	In addition, epidermis of parp-1(-/-) mice did not show increased proliferation rates after treatment with carcinogen.
401	15077172	In the absence of PARP-1, NF-kappaB activation and induction kappaB-target genes did not take place during the promotion of tumor development.
402	15077172	These results suggest that PARP-1 abolition impairs the promotion of skin carcinogenesis interfering with the activation of NF-kappaB and might have an important implication in targeting PARP-1 as a new antineoplastic therapeutic approach.
403	15077172	Crosstalk between PARP-1 and NF-kappaB modulates the promotion of skin neoplasia.
404	15077172	Poly (ADP-ribose) polymerase-1 (PARP-1)-deficient mice are protected against septic shock, type I diabetes, stroke and inflammation.
405	15077172	Here, we report that PARP-1-deficient mice display a strikingly reduced susceptibility to skin carcinogenesis.
406	15077172	In parp-1(-/-) mice, development of papilloma-like premalignant lesions induced with DMBA and TPA, is strongly delayed and the final number of tumor-bearing mice and total tumor number were significantly reduced.
407	15077172	In addition, epidermis of parp-1(-/-) mice did not show increased proliferation rates after treatment with carcinogen.
408	15077172	In the absence of PARP-1, NF-kappaB activation and induction kappaB-target genes did not take place during the promotion of tumor development.
409	15077172	These results suggest that PARP-1 abolition impairs the promotion of skin carcinogenesis interfering with the activation of NF-kappaB and might have an important implication in targeting PARP-1 as a new antineoplastic therapeutic approach.
410	15077172	Crosstalk between PARP-1 and NF-kappaB modulates the promotion of skin neoplasia.
411	15077172	Poly (ADP-ribose) polymerase-1 (PARP-1)-deficient mice are protected against septic shock, type I diabetes, stroke and inflammation.
412	15077172	Here, we report that PARP-1-deficient mice display a strikingly reduced susceptibility to skin carcinogenesis.
413	15077172	In parp-1(-/-) mice, development of papilloma-like premalignant lesions induced with DMBA and TPA, is strongly delayed and the final number of tumor-bearing mice and total tumor number were significantly reduced.
414	15077172	In addition, epidermis of parp-1(-/-) mice did not show increased proliferation rates after treatment with carcinogen.
415	15077172	In the absence of PARP-1, NF-kappaB activation and induction kappaB-target genes did not take place during the promotion of tumor development.
416	15077172	These results suggest that PARP-1 abolition impairs the promotion of skin carcinogenesis interfering with the activation of NF-kappaB and might have an important implication in targeting PARP-1 as a new antineoplastic therapeutic approach.
417	15077172	Crosstalk between PARP-1 and NF-kappaB modulates the promotion of skin neoplasia.
418	15077172	Poly (ADP-ribose) polymerase-1 (PARP-1)-deficient mice are protected against septic shock, type I diabetes, stroke and inflammation.
419	15077172	Here, we report that PARP-1-deficient mice display a strikingly reduced susceptibility to skin carcinogenesis.
420	15077172	In parp-1(-/-) mice, development of papilloma-like premalignant lesions induced with DMBA and TPA, is strongly delayed and the final number of tumor-bearing mice and total tumor number were significantly reduced.
421	15077172	In addition, epidermis of parp-1(-/-) mice did not show increased proliferation rates after treatment with carcinogen.
422	15077172	In the absence of PARP-1, NF-kappaB activation and induction kappaB-target genes did not take place during the promotion of tumor development.
423	15077172	These results suggest that PARP-1 abolition impairs the promotion of skin carcinogenesis interfering with the activation of NF-kappaB and might have an important implication in targeting PARP-1 as a new antineoplastic therapeutic approach.
424	15077172	Crosstalk between PARP-1 and NF-kappaB modulates the promotion of skin neoplasia.
425	15077172	Poly (ADP-ribose) polymerase-1 (PARP-1)-deficient mice are protected against septic shock, type I diabetes, stroke and inflammation.
426	15077172	Here, we report that PARP-1-deficient mice display a strikingly reduced susceptibility to skin carcinogenesis.
427	15077172	In parp-1(-/-) mice, development of papilloma-like premalignant lesions induced with DMBA and TPA, is strongly delayed and the final number of tumor-bearing mice and total tumor number were significantly reduced.
428	15077172	In addition, epidermis of parp-1(-/-) mice did not show increased proliferation rates after treatment with carcinogen.
429	15077172	In the absence of PARP-1, NF-kappaB activation and induction kappaB-target genes did not take place during the promotion of tumor development.
430	15077172	These results suggest that PARP-1 abolition impairs the promotion of skin carcinogenesis interfering with the activation of NF-kappaB and might have an important implication in targeting PARP-1 as a new antineoplastic therapeutic approach.
431	15077172	Crosstalk between PARP-1 and NF-kappaB modulates the promotion of skin neoplasia.
432	15077172	Poly (ADP-ribose) polymerase-1 (PARP-1)-deficient mice are protected against septic shock, type I diabetes, stroke and inflammation.
433	15077172	Here, we report that PARP-1-deficient mice display a strikingly reduced susceptibility to skin carcinogenesis.
434	15077172	In parp-1(-/-) mice, development of papilloma-like premalignant lesions induced with DMBA and TPA, is strongly delayed and the final number of tumor-bearing mice and total tumor number were significantly reduced.
435	15077172	In addition, epidermis of parp-1(-/-) mice did not show increased proliferation rates after treatment with carcinogen.
436	15077172	In the absence of PARP-1, NF-kappaB activation and induction kappaB-target genes did not take place during the promotion of tumor development.
437	15077172	These results suggest that PARP-1 abolition impairs the promotion of skin carcinogenesis interfering with the activation of NF-kappaB and might have an important implication in targeting PARP-1 as a new antineoplastic therapeutic approach.
438	15282315	This posttranslational modification is regulated by the synthesizing enzyme poly(ADP-ribose) polymerase 1 (PARP-1) and the degrading enzyme poly(ADP-ribose) glycohydrolase (PARG).
439	15282315	Although the role of PARP-1 in response to DNA damage has been studied extensively, the function of PARG and the impact of poly(ADP-ribose) homeostasis in various cellular processes are largely unknown.
440	15282315	Here we show that by gene targeting in embryonic stem cells and mice, we specifically deleted the 110-kDa PARG protein (PARG(110)) normally found in the nucleus and that depletion of PARG(110) severely compromised the automodification of PARP-1 in vivo.
441	15282315	This posttranslational modification is regulated by the synthesizing enzyme poly(ADP-ribose) polymerase 1 (PARP-1) and the degrading enzyme poly(ADP-ribose) glycohydrolase (PARG).
442	15282315	Although the role of PARP-1 in response to DNA damage has been studied extensively, the function of PARG and the impact of poly(ADP-ribose) homeostasis in various cellular processes are largely unknown.
443	15282315	Here we show that by gene targeting in embryonic stem cells and mice, we specifically deleted the 110-kDa PARG protein (PARG(110)) normally found in the nucleus and that depletion of PARG(110) severely compromised the automodification of PARP-1 in vivo.
444	15282315	This posttranslational modification is regulated by the synthesizing enzyme poly(ADP-ribose) polymerase 1 (PARP-1) and the degrading enzyme poly(ADP-ribose) glycohydrolase (PARG).
445	15282315	Although the role of PARP-1 in response to DNA damage has been studied extensively, the function of PARG and the impact of poly(ADP-ribose) homeostasis in various cellular processes are largely unknown.
446	15282315	Here we show that by gene targeting in embryonic stem cells and mice, we specifically deleted the 110-kDa PARG protein (PARG(110)) normally found in the nucleus and that depletion of PARG(110) severely compromised the automodification of PARP-1 in vivo.
447	15300792	The best characterised and first discovered member of this multiprotein family is PARP-1.
448	15300792	Moderate activation of PARP-1 facilitates the efficient repair of DNA damage arising from monofunctional alkylating agents, reactive oxygen species or ionising radiation, but severe genotoxic stress leads to rapid energy consumption and subsequently to necrotic cell death.
449	15300792	The latter aspect of PARP-1 activity has been implicated in the pathogenesis of various clinical conditions such as shock, ischaemia-reperfusion and diabetes.
450	15300792	The best characterised and first discovered member of this multiprotein family is PARP-1.
451	15300792	Moderate activation of PARP-1 facilitates the efficient repair of DNA damage arising from monofunctional alkylating agents, reactive oxygen species or ionising radiation, but severe genotoxic stress leads to rapid energy consumption and subsequently to necrotic cell death.
452	15300792	The latter aspect of PARP-1 activity has been implicated in the pathogenesis of various clinical conditions such as shock, ischaemia-reperfusion and diabetes.
453	15300792	The best characterised and first discovered member of this multiprotein family is PARP-1.
454	15300792	Moderate activation of PARP-1 facilitates the efficient repair of DNA damage arising from monofunctional alkylating agents, reactive oxygen species or ionising radiation, but severe genotoxic stress leads to rapid energy consumption and subsequently to necrotic cell death.
455	15300792	The latter aspect of PARP-1 activity has been implicated in the pathogenesis of various clinical conditions such as shock, ischaemia-reperfusion and diabetes.
456	15561303	The best studied of these enzymes (PARP-1) is involved in the cellular response to DNA damage so that in the event of irreparable DNA damage overactivation of PARP-1 leads to necrotic cell death.
457	15561303	Inhibitors of PARP-1 activity in combination with DNA-binding antitumor drugs may constitute a suitable strategy in cancer chemotherapy.
458	15561303	The best studied of these enzymes (PARP-1) is involved in the cellular response to DNA damage so that in the event of irreparable DNA damage overactivation of PARP-1 leads to necrotic cell death.
459	15561303	Inhibitors of PARP-1 activity in combination with DNA-binding antitumor drugs may constitute a suitable strategy in cancer chemotherapy.
460	15855333	A key event in this cascade is the activation of poly(ADP-ribose) polymerase-1 (PARP-1).
461	15855333	Activated PARP-1 consumes cytosolic NAD, and because NAD is required for glycolysis, hypoglycemia-induced PARP-1 activation may render cells unable to use glucose even when glucose availability is restored.
462	15855333	These results suggest that pyruvate may significantly improve the outcome after severe hypoglycemia by circumventing a sustained impairment in neuronal glucose utilization resulting from PARP-1 activation.
463	15855333	A key event in this cascade is the activation of poly(ADP-ribose) polymerase-1 (PARP-1).
464	15855333	Activated PARP-1 consumes cytosolic NAD, and because NAD is required for glycolysis, hypoglycemia-induced PARP-1 activation may render cells unable to use glucose even when glucose availability is restored.
465	15855333	These results suggest that pyruvate may significantly improve the outcome after severe hypoglycemia by circumventing a sustained impairment in neuronal glucose utilization resulting from PARP-1 activation.
466	15855333	A key event in this cascade is the activation of poly(ADP-ribose) polymerase-1 (PARP-1).
467	15855333	Activated PARP-1 consumes cytosolic NAD, and because NAD is required for glycolysis, hypoglycemia-induced PARP-1 activation may render cells unable to use glucose even when glucose availability is restored.
468	15855333	These results suggest that pyruvate may significantly improve the outcome after severe hypoglycemia by circumventing a sustained impairment in neuronal glucose utilization resulting from PARP-1 activation.
469	15868400	PARP-1 is a nuclear enzyme activated by DNA breaks.
470	15868400	Activated PARP-1 cleaves NAD into nicotinamide and ADP-ribose and polymerizes the latter covalently coupled to nuclear acceptor proteins.
471	15868400	On the 'dark side' of poly(ADP-ribosyl)ation, PARP-1 activation has been shown to contribute to tissue injury in shock, diabetes, myocardial or cerebral ischemia reperfusion and various forms of inflammation, as proven by pharmacological studies as well as experiments utilizing PARP-1 knockout animals.
472	15868400	To our current knowledge, two mechanisms are responsible for the beneficial effects of PARP inhibitors in inflammatory, neurodegenerative and ischemia-reperfusion-based diseases: (i) inhibition of cell death caused by over-activation of PARP-1; (ii) inhibition of inflammatory signal transduction and production of inflammatory mediators.
473	15868400	Here we review the possible regulatory mechanisms (e.g. calcium signaling, metabolism, density-dependent signaling, kinase cascades) of the PARP-1-mediated cell death pathway and discuss recent developments shedding new light on the complex role of PARP-1 in the regulation of the expression of inflammatory mediators.
474	15868400	PARP-1 is a nuclear enzyme activated by DNA breaks.
475	15868400	Activated PARP-1 cleaves NAD into nicotinamide and ADP-ribose and polymerizes the latter covalently coupled to nuclear acceptor proteins.
476	15868400	On the 'dark side' of poly(ADP-ribosyl)ation, PARP-1 activation has been shown to contribute to tissue injury in shock, diabetes, myocardial or cerebral ischemia reperfusion and various forms of inflammation, as proven by pharmacological studies as well as experiments utilizing PARP-1 knockout animals.
477	15868400	To our current knowledge, two mechanisms are responsible for the beneficial effects of PARP inhibitors in inflammatory, neurodegenerative and ischemia-reperfusion-based diseases: (i) inhibition of cell death caused by over-activation of PARP-1; (ii) inhibition of inflammatory signal transduction and production of inflammatory mediators.
478	15868400	Here we review the possible regulatory mechanisms (e.g. calcium signaling, metabolism, density-dependent signaling, kinase cascades) of the PARP-1-mediated cell death pathway and discuss recent developments shedding new light on the complex role of PARP-1 in the regulation of the expression of inflammatory mediators.
479	15868400	PARP-1 is a nuclear enzyme activated by DNA breaks.
480	15868400	Activated PARP-1 cleaves NAD into nicotinamide and ADP-ribose and polymerizes the latter covalently coupled to nuclear acceptor proteins.
481	15868400	On the 'dark side' of poly(ADP-ribosyl)ation, PARP-1 activation has been shown to contribute to tissue injury in shock, diabetes, myocardial or cerebral ischemia reperfusion and various forms of inflammation, as proven by pharmacological studies as well as experiments utilizing PARP-1 knockout animals.
482	15868400	To our current knowledge, two mechanisms are responsible for the beneficial effects of PARP inhibitors in inflammatory, neurodegenerative and ischemia-reperfusion-based diseases: (i) inhibition of cell death caused by over-activation of PARP-1; (ii) inhibition of inflammatory signal transduction and production of inflammatory mediators.
483	15868400	Here we review the possible regulatory mechanisms (e.g. calcium signaling, metabolism, density-dependent signaling, kinase cascades) of the PARP-1-mediated cell death pathway and discuss recent developments shedding new light on the complex role of PARP-1 in the regulation of the expression of inflammatory mediators.
484	15868400	PARP-1 is a nuclear enzyme activated by DNA breaks.
485	15868400	Activated PARP-1 cleaves NAD into nicotinamide and ADP-ribose and polymerizes the latter covalently coupled to nuclear acceptor proteins.
486	15868400	On the 'dark side' of poly(ADP-ribosyl)ation, PARP-1 activation has been shown to contribute to tissue injury in shock, diabetes, myocardial or cerebral ischemia reperfusion and various forms of inflammation, as proven by pharmacological studies as well as experiments utilizing PARP-1 knockout animals.
487	15868400	To our current knowledge, two mechanisms are responsible for the beneficial effects of PARP inhibitors in inflammatory, neurodegenerative and ischemia-reperfusion-based diseases: (i) inhibition of cell death caused by over-activation of PARP-1; (ii) inhibition of inflammatory signal transduction and production of inflammatory mediators.
488	15868400	Here we review the possible regulatory mechanisms (e.g. calcium signaling, metabolism, density-dependent signaling, kinase cascades) of the PARP-1-mediated cell death pathway and discuss recent developments shedding new light on the complex role of PARP-1 in the regulation of the expression of inflammatory mediators.
489	15868400	PARP-1 is a nuclear enzyme activated by DNA breaks.
490	15868400	Activated PARP-1 cleaves NAD into nicotinamide and ADP-ribose and polymerizes the latter covalently coupled to nuclear acceptor proteins.
491	15868400	On the 'dark side' of poly(ADP-ribosyl)ation, PARP-1 activation has been shown to contribute to tissue injury in shock, diabetes, myocardial or cerebral ischemia reperfusion and various forms of inflammation, as proven by pharmacological studies as well as experiments utilizing PARP-1 knockout animals.
492	15868400	To our current knowledge, two mechanisms are responsible for the beneficial effects of PARP inhibitors in inflammatory, neurodegenerative and ischemia-reperfusion-based diseases: (i) inhibition of cell death caused by over-activation of PARP-1; (ii) inhibition of inflammatory signal transduction and production of inflammatory mediators.
493	15868400	Here we review the possible regulatory mechanisms (e.g. calcium signaling, metabolism, density-dependent signaling, kinase cascades) of the PARP-1-mediated cell death pathway and discuss recent developments shedding new light on the complex role of PARP-1 in the regulation of the expression of inflammatory mediators.
494	15895395	Poly(ADP-ribose)polymerase (PARP-1), a nuclear enzyme activated by DNA strand breaks, is involved in DNA repair, aging, inflammation, and neoplastic transformation.
495	15895395	In diabetes, reactive oxygen and nitrogen species occurring in response to hyperglycemia cause DNA damages and PARP-1 activation.
496	15895395	Because circulating mononuclear cells (MNCs) are involved in inflammation mechanisms, these cells were chosen as the experimental model to evaluate PARP-1 levels and activity in patients with type 2 diabetes.
497	15895395	PARP-1 expression and activity were analyzed by semi-quantitative PCR, Western and activity blot, and immunofluorescence microscopy.
498	15895395	PARP-1-mRNA expression was increased in MNCs from all diabetic patients versus controls (P < 0.01), whereas PARP-1 content and activity were significantly lower in diabetic patients (P < 0.0001).
499	15895395	To verify whether low PARP-1 levels and activity were due to a proteolytic effect of caspase-3 like, the latter activation was measured by a fluorimetric assay.
500	15895395	The different PARP-1 behavior in MNCs from patients with type 2 diabetes could therefore be responsible for the abnormal inflammation and infection responses in diabetes.
501	15895395	Poly(ADP-ribose)polymerase (PARP-1), a nuclear enzyme activated by DNA strand breaks, is involved in DNA repair, aging, inflammation, and neoplastic transformation.
502	15895395	In diabetes, reactive oxygen and nitrogen species occurring in response to hyperglycemia cause DNA damages and PARP-1 activation.
503	15895395	Because circulating mononuclear cells (MNCs) are involved in inflammation mechanisms, these cells were chosen as the experimental model to evaluate PARP-1 levels and activity in patients with type 2 diabetes.
504	15895395	PARP-1 expression and activity were analyzed by semi-quantitative PCR, Western and activity blot, and immunofluorescence microscopy.
505	15895395	PARP-1-mRNA expression was increased in MNCs from all diabetic patients versus controls (P < 0.01), whereas PARP-1 content and activity were significantly lower in diabetic patients (P < 0.0001).
506	15895395	To verify whether low PARP-1 levels and activity were due to a proteolytic effect of caspase-3 like, the latter activation was measured by a fluorimetric assay.
507	15895395	The different PARP-1 behavior in MNCs from patients with type 2 diabetes could therefore be responsible for the abnormal inflammation and infection responses in diabetes.
508	15895395	Poly(ADP-ribose)polymerase (PARP-1), a nuclear enzyme activated by DNA strand breaks, is involved in DNA repair, aging, inflammation, and neoplastic transformation.
509	15895395	In diabetes, reactive oxygen and nitrogen species occurring in response to hyperglycemia cause DNA damages and PARP-1 activation.
510	15895395	Because circulating mononuclear cells (MNCs) are involved in inflammation mechanisms, these cells were chosen as the experimental model to evaluate PARP-1 levels and activity in patients with type 2 diabetes.
511	15895395	PARP-1 expression and activity were analyzed by semi-quantitative PCR, Western and activity blot, and immunofluorescence microscopy.
512	15895395	PARP-1-mRNA expression was increased in MNCs from all diabetic patients versus controls (P < 0.01), whereas PARP-1 content and activity were significantly lower in diabetic patients (P < 0.0001).
513	15895395	To verify whether low PARP-1 levels and activity were due to a proteolytic effect of caspase-3 like, the latter activation was measured by a fluorimetric assay.
514	15895395	The different PARP-1 behavior in MNCs from patients with type 2 diabetes could therefore be responsible for the abnormal inflammation and infection responses in diabetes.
515	15895395	Poly(ADP-ribose)polymerase (PARP-1), a nuclear enzyme activated by DNA strand breaks, is involved in DNA repair, aging, inflammation, and neoplastic transformation.
516	15895395	In diabetes, reactive oxygen and nitrogen species occurring in response to hyperglycemia cause DNA damages and PARP-1 activation.
517	15895395	Because circulating mononuclear cells (MNCs) are involved in inflammation mechanisms, these cells were chosen as the experimental model to evaluate PARP-1 levels and activity in patients with type 2 diabetes.
518	15895395	PARP-1 expression and activity were analyzed by semi-quantitative PCR, Western and activity blot, and immunofluorescence microscopy.
519	15895395	PARP-1-mRNA expression was increased in MNCs from all diabetic patients versus controls (P < 0.01), whereas PARP-1 content and activity were significantly lower in diabetic patients (P < 0.0001).
520	15895395	To verify whether low PARP-1 levels and activity were due to a proteolytic effect of caspase-3 like, the latter activation was measured by a fluorimetric assay.
521	15895395	The different PARP-1 behavior in MNCs from patients with type 2 diabetes could therefore be responsible for the abnormal inflammation and infection responses in diabetes.
522	15895395	Poly(ADP-ribose)polymerase (PARP-1), a nuclear enzyme activated by DNA strand breaks, is involved in DNA repair, aging, inflammation, and neoplastic transformation.
523	15895395	In diabetes, reactive oxygen and nitrogen species occurring in response to hyperglycemia cause DNA damages and PARP-1 activation.
524	15895395	Because circulating mononuclear cells (MNCs) are involved in inflammation mechanisms, these cells were chosen as the experimental model to evaluate PARP-1 levels and activity in patients with type 2 diabetes.
525	15895395	PARP-1 expression and activity were analyzed by semi-quantitative PCR, Western and activity blot, and immunofluorescence microscopy.
526	15895395	PARP-1-mRNA expression was increased in MNCs from all diabetic patients versus controls (P < 0.01), whereas PARP-1 content and activity were significantly lower in diabetic patients (P < 0.0001).
527	15895395	To verify whether low PARP-1 levels and activity were due to a proteolytic effect of caspase-3 like, the latter activation was measured by a fluorimetric assay.
528	15895395	The different PARP-1 behavior in MNCs from patients with type 2 diabetes could therefore be responsible for the abnormal inflammation and infection responses in diabetes.
529	15895395	Poly(ADP-ribose)polymerase (PARP-1), a nuclear enzyme activated by DNA strand breaks, is involved in DNA repair, aging, inflammation, and neoplastic transformation.
530	15895395	In diabetes, reactive oxygen and nitrogen species occurring in response to hyperglycemia cause DNA damages and PARP-1 activation.
531	15895395	Because circulating mononuclear cells (MNCs) are involved in inflammation mechanisms, these cells were chosen as the experimental model to evaluate PARP-1 levels and activity in patients with type 2 diabetes.
532	15895395	PARP-1 expression and activity were analyzed by semi-quantitative PCR, Western and activity blot, and immunofluorescence microscopy.
533	15895395	PARP-1-mRNA expression was increased in MNCs from all diabetic patients versus controls (P < 0.01), whereas PARP-1 content and activity were significantly lower in diabetic patients (P < 0.0001).
534	15895395	To verify whether low PARP-1 levels and activity were due to a proteolytic effect of caspase-3 like, the latter activation was measured by a fluorimetric assay.
535	15895395	The different PARP-1 behavior in MNCs from patients with type 2 diabetes could therefore be responsible for the abnormal inflammation and infection responses in diabetes.
536	15895395	Poly(ADP-ribose)polymerase (PARP-1), a nuclear enzyme activated by DNA strand breaks, is involved in DNA repair, aging, inflammation, and neoplastic transformation.
537	15895395	In diabetes, reactive oxygen and nitrogen species occurring in response to hyperglycemia cause DNA damages and PARP-1 activation.
538	15895395	Because circulating mononuclear cells (MNCs) are involved in inflammation mechanisms, these cells were chosen as the experimental model to evaluate PARP-1 levels and activity in patients with type 2 diabetes.
539	15895395	PARP-1 expression and activity were analyzed by semi-quantitative PCR, Western and activity blot, and immunofluorescence microscopy.
540	15895395	PARP-1-mRNA expression was increased in MNCs from all diabetic patients versus controls (P < 0.01), whereas PARP-1 content and activity were significantly lower in diabetic patients (P < 0.0001).
541	15895395	To verify whether low PARP-1 levels and activity were due to a proteolytic effect of caspase-3 like, the latter activation was measured by a fluorimetric assay.
542	15895395	The different PARP-1 behavior in MNCs from patients with type 2 diabetes could therefore be responsible for the abnormal inflammation and infection responses in diabetes.
543	15911336	Recent data from three laboratories also support the role of poly(ADP-ribose) polymerase-1 (PARP-1) activation in asthma.
544	15911336	Similarly to other inflammatory conditions, the protective effects of PARP inhibition and the PARP-1 knock out phenotype in asthma models have been attributed to inhibition of inflammatory signal transduction (mainly via NF-kappaB) and of oxidative stress-induced cell dysfunction and tissue injury.
545	15911336	The role of PARP-1 in other oxidative stress-related lung diseases such as asbestosis, silicosis, acute respiratory distress syndrome and ischemia-reperfusion injury is also reviewed.
546	15911336	Recent data from three laboratories also support the role of poly(ADP-ribose) polymerase-1 (PARP-1) activation in asthma.
547	15911336	Similarly to other inflammatory conditions, the protective effects of PARP inhibition and the PARP-1 knock out phenotype in asthma models have been attributed to inhibition of inflammatory signal transduction (mainly via NF-kappaB) and of oxidative stress-induced cell dysfunction and tissue injury.
548	15911336	The role of PARP-1 in other oxidative stress-related lung diseases such as asbestosis, silicosis, acute respiratory distress syndrome and ischemia-reperfusion injury is also reviewed.
549	15911336	Recent data from three laboratories also support the role of poly(ADP-ribose) polymerase-1 (PARP-1) activation in asthma.
550	15911336	Similarly to other inflammatory conditions, the protective effects of PARP inhibition and the PARP-1 knock out phenotype in asthma models have been attributed to inhibition of inflammatory signal transduction (mainly via NF-kappaB) and of oxidative stress-induced cell dysfunction and tissue injury.
551	15911336	The role of PARP-1 in other oxidative stress-related lung diseases such as asbestosis, silicosis, acute respiratory distress syndrome and ischemia-reperfusion injury is also reviewed.
552	15953818	Poly(ADP-ribose) polymerase (PARP)-1 is a DNA nick sensor that transforms ADP-ribose from betaNAD+ in the form of polymer to over 40 nuclear proteins, particularly to histones, several transcription factors, and PARP itself, modulating their activities and functions.
553	15953818	PARP-1 activated by DNA breaks facilitates transcription, replication, and DNA base excision repair.
554	15953818	The last studies indicate that PARP-1 is the new nuclear target for fast signals evoked in cell membranes by depolarization and cholinergic and glutaminergic receptors stimulation.
555	15953818	Excessive activation of PARP-1 by peroxynitrate-evoked DNA damage during oxidative stress can cause cell death by NAD+/ATP depletion after ischemia-reperfusion injury, inflammation, and diabetes mellitus.
556	15953818	The PARP-1 through interaction with nuclear factor-kappaB, p53, and other transcription factors might significantly modulate cell survival and death and a type of death pathway.
557	15953818	The pharmacological modulation of PARP-1 might offer a new effective approach for neuroprotection.
558	15953818	Poly(ADP-ribose) polymerase (PARP)-1 is a DNA nick sensor that transforms ADP-ribose from betaNAD+ in the form of polymer to over 40 nuclear proteins, particularly to histones, several transcription factors, and PARP itself, modulating their activities and functions.
559	15953818	PARP-1 activated by DNA breaks facilitates transcription, replication, and DNA base excision repair.
560	15953818	The last studies indicate that PARP-1 is the new nuclear target for fast signals evoked in cell membranes by depolarization and cholinergic and glutaminergic receptors stimulation.
561	15953818	Excessive activation of PARP-1 by peroxynitrate-evoked DNA damage during oxidative stress can cause cell death by NAD+/ATP depletion after ischemia-reperfusion injury, inflammation, and diabetes mellitus.
562	15953818	The PARP-1 through interaction with nuclear factor-kappaB, p53, and other transcription factors might significantly modulate cell survival and death and a type of death pathway.
563	15953818	The pharmacological modulation of PARP-1 might offer a new effective approach for neuroprotection.
564	15953818	Poly(ADP-ribose) polymerase (PARP)-1 is a DNA nick sensor that transforms ADP-ribose from betaNAD+ in the form of polymer to over 40 nuclear proteins, particularly to histones, several transcription factors, and PARP itself, modulating their activities and functions.
565	15953818	PARP-1 activated by DNA breaks facilitates transcription, replication, and DNA base excision repair.
566	15953818	The last studies indicate that PARP-1 is the new nuclear target for fast signals evoked in cell membranes by depolarization and cholinergic and glutaminergic receptors stimulation.
567	15953818	Excessive activation of PARP-1 by peroxynitrate-evoked DNA damage during oxidative stress can cause cell death by NAD+/ATP depletion after ischemia-reperfusion injury, inflammation, and diabetes mellitus.
568	15953818	The PARP-1 through interaction with nuclear factor-kappaB, p53, and other transcription factors might significantly modulate cell survival and death and a type of death pathway.
569	15953818	The pharmacological modulation of PARP-1 might offer a new effective approach for neuroprotection.
570	15953818	Poly(ADP-ribose) polymerase (PARP)-1 is a DNA nick sensor that transforms ADP-ribose from betaNAD+ in the form of polymer to over 40 nuclear proteins, particularly to histones, several transcription factors, and PARP itself, modulating their activities and functions.
571	15953818	PARP-1 activated by DNA breaks facilitates transcription, replication, and DNA base excision repair.
572	15953818	The last studies indicate that PARP-1 is the new nuclear target for fast signals evoked in cell membranes by depolarization and cholinergic and glutaminergic receptors stimulation.
573	15953818	Excessive activation of PARP-1 by peroxynitrate-evoked DNA damage during oxidative stress can cause cell death by NAD+/ATP depletion after ischemia-reperfusion injury, inflammation, and diabetes mellitus.
574	15953818	The PARP-1 through interaction with nuclear factor-kappaB, p53, and other transcription factors might significantly modulate cell survival and death and a type of death pathway.
575	15953818	The pharmacological modulation of PARP-1 might offer a new effective approach for neuroprotection.
576	15953818	Poly(ADP-ribose) polymerase (PARP)-1 is a DNA nick sensor that transforms ADP-ribose from betaNAD+ in the form of polymer to over 40 nuclear proteins, particularly to histones, several transcription factors, and PARP itself, modulating their activities and functions.
577	15953818	PARP-1 activated by DNA breaks facilitates transcription, replication, and DNA base excision repair.
578	15953818	The last studies indicate that PARP-1 is the new nuclear target for fast signals evoked in cell membranes by depolarization and cholinergic and glutaminergic receptors stimulation.
579	15953818	Excessive activation of PARP-1 by peroxynitrate-evoked DNA damage during oxidative stress can cause cell death by NAD+/ATP depletion after ischemia-reperfusion injury, inflammation, and diabetes mellitus.
580	15953818	The PARP-1 through interaction with nuclear factor-kappaB, p53, and other transcription factors might significantly modulate cell survival and death and a type of death pathway.
581	15953818	The pharmacological modulation of PARP-1 might offer a new effective approach for neuroprotection.
582	15953818	Poly(ADP-ribose) polymerase (PARP)-1 is a DNA nick sensor that transforms ADP-ribose from betaNAD+ in the form of polymer to over 40 nuclear proteins, particularly to histones, several transcription factors, and PARP itself, modulating their activities and functions.
583	15953818	PARP-1 activated by DNA breaks facilitates transcription, replication, and DNA base excision repair.
584	15953818	The last studies indicate that PARP-1 is the new nuclear target for fast signals evoked in cell membranes by depolarization and cholinergic and glutaminergic receptors stimulation.
585	15953818	Excessive activation of PARP-1 by peroxynitrate-evoked DNA damage during oxidative stress can cause cell death by NAD+/ATP depletion after ischemia-reperfusion injury, inflammation, and diabetes mellitus.
586	15953818	The PARP-1 through interaction with nuclear factor-kappaB, p53, and other transcription factors might significantly modulate cell survival and death and a type of death pathway.
587	15953818	The pharmacological modulation of PARP-1 might offer a new effective approach for neuroprotection.
588	15982573	Synthesis and in vivo evaluation of [11C]PJ34, a potential radiotracer for imaging the role of PARP-1 in necrosis.
589	15982573	Poly(ADP-ribose) polymerase-1 (PARP-1) is an abundant nuclear enzyme of eukaryotic cells that has been implicated in response to DNA injury.
590	15982573	PARP-1 detects single-strand DNA breaks induced by a variety of genotoxic insults.
591	15982573	A hyperactivation of PARP-1 is believed to play a critical role in tissues undergoing cellular death by necrosis.
592	15982573	Therefore, a radiotracer that could image PARP-1 levels with PET could provide a useful tool in measuring necrosis in a variety of pathological conditions.
593	15982573	The phenanthridinone derivative, 2-(dimethylamino)-N-(5,6-dihydro-6-oxophenanthridin-2-yl)acetamide (PJ34), has a high affinity for PARP-1 (IC(50) = 20 nM) and is a suitable lead compound for PET radiotracer development.
594	15982573	Preliminary in vivo biodistribution studies in a rodent model of diabetes indicate that [(11)C]PJ34 displays a high uptake in tissues where PARP-1 is hyperactivated.
595	15982573	Synthesis and in vivo evaluation of [11C]PJ34, a potential radiotracer for imaging the role of PARP-1 in necrosis.
596	15982573	Poly(ADP-ribose) polymerase-1 (PARP-1) is an abundant nuclear enzyme of eukaryotic cells that has been implicated in response to DNA injury.
597	15982573	PARP-1 detects single-strand DNA breaks induced by a variety of genotoxic insults.
598	15982573	A hyperactivation of PARP-1 is believed to play a critical role in tissues undergoing cellular death by necrosis.
599	15982573	Therefore, a radiotracer that could image PARP-1 levels with PET could provide a useful tool in measuring necrosis in a variety of pathological conditions.
600	15982573	The phenanthridinone derivative, 2-(dimethylamino)-N-(5,6-dihydro-6-oxophenanthridin-2-yl)acetamide (PJ34), has a high affinity for PARP-1 (IC(50) = 20 nM) and is a suitable lead compound for PET radiotracer development.
601	15982573	Preliminary in vivo biodistribution studies in a rodent model of diabetes indicate that [(11)C]PJ34 displays a high uptake in tissues where PARP-1 is hyperactivated.
602	15982573	Synthesis and in vivo evaluation of [11C]PJ34, a potential radiotracer for imaging the role of PARP-1 in necrosis.
603	15982573	Poly(ADP-ribose) polymerase-1 (PARP-1) is an abundant nuclear enzyme of eukaryotic cells that has been implicated in response to DNA injury.
604	15982573	PARP-1 detects single-strand DNA breaks induced by a variety of genotoxic insults.
605	15982573	A hyperactivation of PARP-1 is believed to play a critical role in tissues undergoing cellular death by necrosis.
606	15982573	Therefore, a radiotracer that could image PARP-1 levels with PET could provide a useful tool in measuring necrosis in a variety of pathological conditions.
607	15982573	The phenanthridinone derivative, 2-(dimethylamino)-N-(5,6-dihydro-6-oxophenanthridin-2-yl)acetamide (PJ34), has a high affinity for PARP-1 (IC(50) = 20 nM) and is a suitable lead compound for PET radiotracer development.
608	15982573	Preliminary in vivo biodistribution studies in a rodent model of diabetes indicate that [(11)C]PJ34 displays a high uptake in tissues where PARP-1 is hyperactivated.
609	15982573	Synthesis and in vivo evaluation of [11C]PJ34, a potential radiotracer for imaging the role of PARP-1 in necrosis.
610	15982573	Poly(ADP-ribose) polymerase-1 (PARP-1) is an abundant nuclear enzyme of eukaryotic cells that has been implicated in response to DNA injury.
611	15982573	PARP-1 detects single-strand DNA breaks induced by a variety of genotoxic insults.
612	15982573	A hyperactivation of PARP-1 is believed to play a critical role in tissues undergoing cellular death by necrosis.
613	15982573	Therefore, a radiotracer that could image PARP-1 levels with PET could provide a useful tool in measuring necrosis in a variety of pathological conditions.
614	15982573	The phenanthridinone derivative, 2-(dimethylamino)-N-(5,6-dihydro-6-oxophenanthridin-2-yl)acetamide (PJ34), has a high affinity for PARP-1 (IC(50) = 20 nM) and is a suitable lead compound for PET radiotracer development.
615	15982573	Preliminary in vivo biodistribution studies in a rodent model of diabetes indicate that [(11)C]PJ34 displays a high uptake in tissues where PARP-1 is hyperactivated.
616	15982573	Synthesis and in vivo evaluation of [11C]PJ34, a potential radiotracer for imaging the role of PARP-1 in necrosis.
617	15982573	Poly(ADP-ribose) polymerase-1 (PARP-1) is an abundant nuclear enzyme of eukaryotic cells that has been implicated in response to DNA injury.
618	15982573	PARP-1 detects single-strand DNA breaks induced by a variety of genotoxic insults.
619	15982573	A hyperactivation of PARP-1 is believed to play a critical role in tissues undergoing cellular death by necrosis.
620	15982573	Therefore, a radiotracer that could image PARP-1 levels with PET could provide a useful tool in measuring necrosis in a variety of pathological conditions.
621	15982573	The phenanthridinone derivative, 2-(dimethylamino)-N-(5,6-dihydro-6-oxophenanthridin-2-yl)acetamide (PJ34), has a high affinity for PARP-1 (IC(50) = 20 nM) and is a suitable lead compound for PET radiotracer development.
622	15982573	Preliminary in vivo biodistribution studies in a rodent model of diabetes indicate that [(11)C]PJ34 displays a high uptake in tissues where PARP-1 is hyperactivated.
623	15982573	Synthesis and in vivo evaluation of [11C]PJ34, a potential radiotracer for imaging the role of PARP-1 in necrosis.
624	15982573	Poly(ADP-ribose) polymerase-1 (PARP-1) is an abundant nuclear enzyme of eukaryotic cells that has been implicated in response to DNA injury.
625	15982573	PARP-1 detects single-strand DNA breaks induced by a variety of genotoxic insults.
626	15982573	A hyperactivation of PARP-1 is believed to play a critical role in tissues undergoing cellular death by necrosis.
627	15982573	Therefore, a radiotracer that could image PARP-1 levels with PET could provide a useful tool in measuring necrosis in a variety of pathological conditions.
628	15982573	The phenanthridinone derivative, 2-(dimethylamino)-N-(5,6-dihydro-6-oxophenanthridin-2-yl)acetamide (PJ34), has a high affinity for PARP-1 (IC(50) = 20 nM) and is a suitable lead compound for PET radiotracer development.
629	15982573	Preliminary in vivo biodistribution studies in a rodent model of diabetes indicate that [(11)C]PJ34 displays a high uptake in tissues where PARP-1 is hyperactivated.
630	15982573	Synthesis and in vivo evaluation of [11C]PJ34, a potential radiotracer for imaging the role of PARP-1 in necrosis.
631	15982573	Poly(ADP-ribose) polymerase-1 (PARP-1) is an abundant nuclear enzyme of eukaryotic cells that has been implicated in response to DNA injury.
632	15982573	PARP-1 detects single-strand DNA breaks induced by a variety of genotoxic insults.
633	15982573	A hyperactivation of PARP-1 is believed to play a critical role in tissues undergoing cellular death by necrosis.
634	15982573	Therefore, a radiotracer that could image PARP-1 levels with PET could provide a useful tool in measuring necrosis in a variety of pathological conditions.
635	15982573	The phenanthridinone derivative, 2-(dimethylamino)-N-(5,6-dihydro-6-oxophenanthridin-2-yl)acetamide (PJ34), has a high affinity for PARP-1 (IC(50) = 20 nM) and is a suitable lead compound for PET radiotracer development.
636	15982573	Preliminary in vivo biodistribution studies in a rodent model of diabetes indicate that [(11)C]PJ34 displays a high uptake in tissues where PARP-1 is hyperactivated.
637	16026317	Whereas an 18 member superfamily of poly(ADP-ribose) polymerase (PARP) enzymes synthesize poly(ADP-ribose) (PAR), a single protein, PAR glycohydrolase (PARG) is responsible for the catabolism of the polymer.
638	16026317	PARP-1 accounts for more than 90% of the poly(ADP-ribosyl)ating capacity of the cells.
639	16026317	PARP-1 activated by DNA breaks cleaves NAD(+) into nicotinamide and ADP-ribose and uses the latter to synthesize long branching PAR polymers covalently attached to acceptor proteins including histones, DNA repair enzymes, transcription factors and PARP-1.
640	16026317	Whereas activation of PARP-1 by mild genotoxic stimuli may facilitate DNA repair and cell survival, irreparable DNA damage triggers apoptotic or necrotic cell death.
641	16026317	In apoptosis, early PARP activation may assist the apoptotic cascade [e.g. by stabilizing p53, by mediating the translocation of apoptosis inducing factor (AIF) from the mitochondria to the nucleus or by inhibiting early activation of DNases].
642	16026317	In most severe oxidative stress situations, excessive DNA damage causes over activation of PARP-1, which incapacitates the apoptotic machinery and switches the mode of cell death from apoptosis to necrosis.
643	16026317	Besides serving as a cytotoxic mediator, PARP-1 is also involved in transcriptional regulation, most notably in the NF kappaB and AP-1 driven expression of inflammatory mediators.
644	16026317	Pharmacological inhibition or genetic ablation of PARP-1 provided remarkable protection from tissue injury in various oxidative stress-related disease models ranging from stroke, diabetes, diabetic endothelial dysfunction, myocardial ischemia-reperfusion, shock, Parkinson's disease, arthritis, colitis to dermatitis and uveitis.
645	16026317	These beneficial effects are attributed to inhibition of the PARP-1 mediated suicidal pathway and to reduced expression of inflammatory cytokines and other mediators (e.g. inducible nitric oxide synthase).
646	16026317	Whereas an 18 member superfamily of poly(ADP-ribose) polymerase (PARP) enzymes synthesize poly(ADP-ribose) (PAR), a single protein, PAR glycohydrolase (PARG) is responsible for the catabolism of the polymer.
647	16026317	PARP-1 accounts for more than 90% of the poly(ADP-ribosyl)ating capacity of the cells.
648	16026317	PARP-1 activated by DNA breaks cleaves NAD(+) into nicotinamide and ADP-ribose and uses the latter to synthesize long branching PAR polymers covalently attached to acceptor proteins including histones, DNA repair enzymes, transcription factors and PARP-1.
649	16026317	Whereas activation of PARP-1 by mild genotoxic stimuli may facilitate DNA repair and cell survival, irreparable DNA damage triggers apoptotic or necrotic cell death.
650	16026317	In apoptosis, early PARP activation may assist the apoptotic cascade [e.g. by stabilizing p53, by mediating the translocation of apoptosis inducing factor (AIF) from the mitochondria to the nucleus or by inhibiting early activation of DNases].
651	16026317	In most severe oxidative stress situations, excessive DNA damage causes over activation of PARP-1, which incapacitates the apoptotic machinery and switches the mode of cell death from apoptosis to necrosis.
652	16026317	Besides serving as a cytotoxic mediator, PARP-1 is also involved in transcriptional regulation, most notably in the NF kappaB and AP-1 driven expression of inflammatory mediators.
653	16026317	Pharmacological inhibition or genetic ablation of PARP-1 provided remarkable protection from tissue injury in various oxidative stress-related disease models ranging from stroke, diabetes, diabetic endothelial dysfunction, myocardial ischemia-reperfusion, shock, Parkinson's disease, arthritis, colitis to dermatitis and uveitis.
654	16026317	These beneficial effects are attributed to inhibition of the PARP-1 mediated suicidal pathway and to reduced expression of inflammatory cytokines and other mediators (e.g. inducible nitric oxide synthase).
655	16026317	Whereas an 18 member superfamily of poly(ADP-ribose) polymerase (PARP) enzymes synthesize poly(ADP-ribose) (PAR), a single protein, PAR glycohydrolase (PARG) is responsible for the catabolism of the polymer.
656	16026317	PARP-1 accounts for more than 90% of the poly(ADP-ribosyl)ating capacity of the cells.
657	16026317	PARP-1 activated by DNA breaks cleaves NAD(+) into nicotinamide and ADP-ribose and uses the latter to synthesize long branching PAR polymers covalently attached to acceptor proteins including histones, DNA repair enzymes, transcription factors and PARP-1.
658	16026317	Whereas activation of PARP-1 by mild genotoxic stimuli may facilitate DNA repair and cell survival, irreparable DNA damage triggers apoptotic or necrotic cell death.
659	16026317	In apoptosis, early PARP activation may assist the apoptotic cascade [e.g. by stabilizing p53, by mediating the translocation of apoptosis inducing factor (AIF) from the mitochondria to the nucleus or by inhibiting early activation of DNases].
660	16026317	In most severe oxidative stress situations, excessive DNA damage causes over activation of PARP-1, which incapacitates the apoptotic machinery and switches the mode of cell death from apoptosis to necrosis.
661	16026317	Besides serving as a cytotoxic mediator, PARP-1 is also involved in transcriptional regulation, most notably in the NF kappaB and AP-1 driven expression of inflammatory mediators.
662	16026317	Pharmacological inhibition or genetic ablation of PARP-1 provided remarkable protection from tissue injury in various oxidative stress-related disease models ranging from stroke, diabetes, diabetic endothelial dysfunction, myocardial ischemia-reperfusion, shock, Parkinson's disease, arthritis, colitis to dermatitis and uveitis.
663	16026317	These beneficial effects are attributed to inhibition of the PARP-1 mediated suicidal pathway and to reduced expression of inflammatory cytokines and other mediators (e.g. inducible nitric oxide synthase).
664	16026317	Whereas an 18 member superfamily of poly(ADP-ribose) polymerase (PARP) enzymes synthesize poly(ADP-ribose) (PAR), a single protein, PAR glycohydrolase (PARG) is responsible for the catabolism of the polymer.
665	16026317	PARP-1 accounts for more than 90% of the poly(ADP-ribosyl)ating capacity of the cells.
666	16026317	PARP-1 activated by DNA breaks cleaves NAD(+) into nicotinamide and ADP-ribose and uses the latter to synthesize long branching PAR polymers covalently attached to acceptor proteins including histones, DNA repair enzymes, transcription factors and PARP-1.
667	16026317	Whereas activation of PARP-1 by mild genotoxic stimuli may facilitate DNA repair and cell survival, irreparable DNA damage triggers apoptotic or necrotic cell death.
668	16026317	In apoptosis, early PARP activation may assist the apoptotic cascade [e.g. by stabilizing p53, by mediating the translocation of apoptosis inducing factor (AIF) from the mitochondria to the nucleus or by inhibiting early activation of DNases].
669	16026317	In most severe oxidative stress situations, excessive DNA damage causes over activation of PARP-1, which incapacitates the apoptotic machinery and switches the mode of cell death from apoptosis to necrosis.
670	16026317	Besides serving as a cytotoxic mediator, PARP-1 is also involved in transcriptional regulation, most notably in the NF kappaB and AP-1 driven expression of inflammatory mediators.
671	16026317	Pharmacological inhibition or genetic ablation of PARP-1 provided remarkable protection from tissue injury in various oxidative stress-related disease models ranging from stroke, diabetes, diabetic endothelial dysfunction, myocardial ischemia-reperfusion, shock, Parkinson's disease, arthritis, colitis to dermatitis and uveitis.
672	16026317	These beneficial effects are attributed to inhibition of the PARP-1 mediated suicidal pathway and to reduced expression of inflammatory cytokines and other mediators (e.g. inducible nitric oxide synthase).
673	16026317	Whereas an 18 member superfamily of poly(ADP-ribose) polymerase (PARP) enzymes synthesize poly(ADP-ribose) (PAR), a single protein, PAR glycohydrolase (PARG) is responsible for the catabolism of the polymer.
674	16026317	PARP-1 accounts for more than 90% of the poly(ADP-ribosyl)ating capacity of the cells.
675	16026317	PARP-1 activated by DNA breaks cleaves NAD(+) into nicotinamide and ADP-ribose and uses the latter to synthesize long branching PAR polymers covalently attached to acceptor proteins including histones, DNA repair enzymes, transcription factors and PARP-1.
676	16026317	Whereas activation of PARP-1 by mild genotoxic stimuli may facilitate DNA repair and cell survival, irreparable DNA damage triggers apoptotic or necrotic cell death.
677	16026317	In apoptosis, early PARP activation may assist the apoptotic cascade [e.g. by stabilizing p53, by mediating the translocation of apoptosis inducing factor (AIF) from the mitochondria to the nucleus or by inhibiting early activation of DNases].
678	16026317	In most severe oxidative stress situations, excessive DNA damage causes over activation of PARP-1, which incapacitates the apoptotic machinery and switches the mode of cell death from apoptosis to necrosis.
679	16026317	Besides serving as a cytotoxic mediator, PARP-1 is also involved in transcriptional regulation, most notably in the NF kappaB and AP-1 driven expression of inflammatory mediators.
680	16026317	Pharmacological inhibition or genetic ablation of PARP-1 provided remarkable protection from tissue injury in various oxidative stress-related disease models ranging from stroke, diabetes, diabetic endothelial dysfunction, myocardial ischemia-reperfusion, shock, Parkinson's disease, arthritis, colitis to dermatitis and uveitis.
681	16026317	These beneficial effects are attributed to inhibition of the PARP-1 mediated suicidal pathway and to reduced expression of inflammatory cytokines and other mediators (e.g. inducible nitric oxide synthase).
682	16026317	Whereas an 18 member superfamily of poly(ADP-ribose) polymerase (PARP) enzymes synthesize poly(ADP-ribose) (PAR), a single protein, PAR glycohydrolase (PARG) is responsible for the catabolism of the polymer.
683	16026317	PARP-1 accounts for more than 90% of the poly(ADP-ribosyl)ating capacity of the cells.
684	16026317	PARP-1 activated by DNA breaks cleaves NAD(+) into nicotinamide and ADP-ribose and uses the latter to synthesize long branching PAR polymers covalently attached to acceptor proteins including histones, DNA repair enzymes, transcription factors and PARP-1.
685	16026317	Whereas activation of PARP-1 by mild genotoxic stimuli may facilitate DNA repair and cell survival, irreparable DNA damage triggers apoptotic or necrotic cell death.
686	16026317	In apoptosis, early PARP activation may assist the apoptotic cascade [e.g. by stabilizing p53, by mediating the translocation of apoptosis inducing factor (AIF) from the mitochondria to the nucleus or by inhibiting early activation of DNases].
687	16026317	In most severe oxidative stress situations, excessive DNA damage causes over activation of PARP-1, which incapacitates the apoptotic machinery and switches the mode of cell death from apoptosis to necrosis.
688	16026317	Besides serving as a cytotoxic mediator, PARP-1 is also involved in transcriptional regulation, most notably in the NF kappaB and AP-1 driven expression of inflammatory mediators.
689	16026317	Pharmacological inhibition or genetic ablation of PARP-1 provided remarkable protection from tissue injury in various oxidative stress-related disease models ranging from stroke, diabetes, diabetic endothelial dysfunction, myocardial ischemia-reperfusion, shock, Parkinson's disease, arthritis, colitis to dermatitis and uveitis.
690	16026317	These beneficial effects are attributed to inhibition of the PARP-1 mediated suicidal pathway and to reduced expression of inflammatory cytokines and other mediators (e.g. inducible nitric oxide synthase).
691	16026317	Whereas an 18 member superfamily of poly(ADP-ribose) polymerase (PARP) enzymes synthesize poly(ADP-ribose) (PAR), a single protein, PAR glycohydrolase (PARG) is responsible for the catabolism of the polymer.
692	16026317	PARP-1 accounts for more than 90% of the poly(ADP-ribosyl)ating capacity of the cells.
693	16026317	PARP-1 activated by DNA breaks cleaves NAD(+) into nicotinamide and ADP-ribose and uses the latter to synthesize long branching PAR polymers covalently attached to acceptor proteins including histones, DNA repair enzymes, transcription factors and PARP-1.
694	16026317	Whereas activation of PARP-1 by mild genotoxic stimuli may facilitate DNA repair and cell survival, irreparable DNA damage triggers apoptotic or necrotic cell death.
695	16026317	In apoptosis, early PARP activation may assist the apoptotic cascade [e.g. by stabilizing p53, by mediating the translocation of apoptosis inducing factor (AIF) from the mitochondria to the nucleus or by inhibiting early activation of DNases].
696	16026317	In most severe oxidative stress situations, excessive DNA damage causes over activation of PARP-1, which incapacitates the apoptotic machinery and switches the mode of cell death from apoptosis to necrosis.
697	16026317	Besides serving as a cytotoxic mediator, PARP-1 is also involved in transcriptional regulation, most notably in the NF kappaB and AP-1 driven expression of inflammatory mediators.
698	16026317	Pharmacological inhibition or genetic ablation of PARP-1 provided remarkable protection from tissue injury in various oxidative stress-related disease models ranging from stroke, diabetes, diabetic endothelial dysfunction, myocardial ischemia-reperfusion, shock, Parkinson's disease, arthritis, colitis to dermatitis and uveitis.
699	16026317	These beneficial effects are attributed to inhibition of the PARP-1 mediated suicidal pathway and to reduced expression of inflammatory cytokines and other mediators (e.g. inducible nitric oxide synthase).
700	16181138	A major isoform, PARP-1, has been the target for design of inhibitors for over twenty-five years.
701	16181138	Inhibitors of the activity of PARP-1 have been claimed to have applications in the treatment of many disease states, including cancer, haemorrhagic shock, cardiac infarct, stroke, diabetes, inflammation and retroviral infection, but only recently have PARP-1 inhibitors entered clinical trial.
702	16181138	Most PARP-1 inhibitors mimic the nicotinamide of NAD(+) and the structure-activity relationships are understood in terms of the structure of the catalytic site.
703	16181138	However, five questions remain if PARP-1 inhibitors are to realise their potential in treating human diseases.
704	16181138	Secondly, some potential clinical applications require tissue-selective PARP-1 inhibition; is this possible through pro-drug approaches?
705	16181138	Thirdly, different diseases may require therapeutic PARP-1 inhibition to be either short-term or chronic; are there potential problems associated with chronic inhibition of this DNA-repair process?
706	16181138	Fourthly, PARP-1 is one of at least eighteen isoforms; is isoform-selectivity essential, desirable or even possible?
707	16181138	Fifthly, PARP activity can be inhibited in cells by inhibition of poly(ADP-ribose)-glycohydrolase (PARG); will this be a viable strategy for future drug design?
708	16181138	A major isoform, PARP-1, has been the target for design of inhibitors for over twenty-five years.
709	16181138	Inhibitors of the activity of PARP-1 have been claimed to have applications in the treatment of many disease states, including cancer, haemorrhagic shock, cardiac infarct, stroke, diabetes, inflammation and retroviral infection, but only recently have PARP-1 inhibitors entered clinical trial.
710	16181138	Most PARP-1 inhibitors mimic the nicotinamide of NAD(+) and the structure-activity relationships are understood in terms of the structure of the catalytic site.
711	16181138	However, five questions remain if PARP-1 inhibitors are to realise their potential in treating human diseases.
712	16181138	Secondly, some potential clinical applications require tissue-selective PARP-1 inhibition; is this possible through pro-drug approaches?
713	16181138	Thirdly, different diseases may require therapeutic PARP-1 inhibition to be either short-term or chronic; are there potential problems associated with chronic inhibition of this DNA-repair process?
714	16181138	Fourthly, PARP-1 is one of at least eighteen isoforms; is isoform-selectivity essential, desirable or even possible?
715	16181138	Fifthly, PARP activity can be inhibited in cells by inhibition of poly(ADP-ribose)-glycohydrolase (PARG); will this be a viable strategy for future drug design?
716	16181138	A major isoform, PARP-1, has been the target for design of inhibitors for over twenty-five years.
717	16181138	Inhibitors of the activity of PARP-1 have been claimed to have applications in the treatment of many disease states, including cancer, haemorrhagic shock, cardiac infarct, stroke, diabetes, inflammation and retroviral infection, but only recently have PARP-1 inhibitors entered clinical trial.
718	16181138	Most PARP-1 inhibitors mimic the nicotinamide of NAD(+) and the structure-activity relationships are understood in terms of the structure of the catalytic site.
719	16181138	However, five questions remain if PARP-1 inhibitors are to realise their potential in treating human diseases.
720	16181138	Secondly, some potential clinical applications require tissue-selective PARP-1 inhibition; is this possible through pro-drug approaches?
721	16181138	Thirdly, different diseases may require therapeutic PARP-1 inhibition to be either short-term or chronic; are there potential problems associated with chronic inhibition of this DNA-repair process?
722	16181138	Fourthly, PARP-1 is one of at least eighteen isoforms; is isoform-selectivity essential, desirable or even possible?
723	16181138	Fifthly, PARP activity can be inhibited in cells by inhibition of poly(ADP-ribose)-glycohydrolase (PARG); will this be a viable strategy for future drug design?
724	16181138	A major isoform, PARP-1, has been the target for design of inhibitors for over twenty-five years.
725	16181138	Inhibitors of the activity of PARP-1 have been claimed to have applications in the treatment of many disease states, including cancer, haemorrhagic shock, cardiac infarct, stroke, diabetes, inflammation and retroviral infection, but only recently have PARP-1 inhibitors entered clinical trial.
726	16181138	Most PARP-1 inhibitors mimic the nicotinamide of NAD(+) and the structure-activity relationships are understood in terms of the structure of the catalytic site.
727	16181138	However, five questions remain if PARP-1 inhibitors are to realise their potential in treating human diseases.
728	16181138	Secondly, some potential clinical applications require tissue-selective PARP-1 inhibition; is this possible through pro-drug approaches?
729	16181138	Thirdly, different diseases may require therapeutic PARP-1 inhibition to be either short-term or chronic; are there potential problems associated with chronic inhibition of this DNA-repair process?
730	16181138	Fourthly, PARP-1 is one of at least eighteen isoforms; is isoform-selectivity essential, desirable or even possible?
731	16181138	Fifthly, PARP activity can be inhibited in cells by inhibition of poly(ADP-ribose)-glycohydrolase (PARG); will this be a viable strategy for future drug design?
732	16181138	A major isoform, PARP-1, has been the target for design of inhibitors for over twenty-five years.
733	16181138	Inhibitors of the activity of PARP-1 have been claimed to have applications in the treatment of many disease states, including cancer, haemorrhagic shock, cardiac infarct, stroke, diabetes, inflammation and retroviral infection, but only recently have PARP-1 inhibitors entered clinical trial.
734	16181138	Most PARP-1 inhibitors mimic the nicotinamide of NAD(+) and the structure-activity relationships are understood in terms of the structure of the catalytic site.
735	16181138	However, five questions remain if PARP-1 inhibitors are to realise their potential in treating human diseases.
736	16181138	Secondly, some potential clinical applications require tissue-selective PARP-1 inhibition; is this possible through pro-drug approaches?
737	16181138	Thirdly, different diseases may require therapeutic PARP-1 inhibition to be either short-term or chronic; are there potential problems associated with chronic inhibition of this DNA-repair process?
738	16181138	Fourthly, PARP-1 is one of at least eighteen isoforms; is isoform-selectivity essential, desirable or even possible?
739	16181138	Fifthly, PARP activity can be inhibited in cells by inhibition of poly(ADP-ribose)-glycohydrolase (PARG); will this be a viable strategy for future drug design?
740	16181138	A major isoform, PARP-1, has been the target for design of inhibitors for over twenty-five years.
741	16181138	Inhibitors of the activity of PARP-1 have been claimed to have applications in the treatment of many disease states, including cancer, haemorrhagic shock, cardiac infarct, stroke, diabetes, inflammation and retroviral infection, but only recently have PARP-1 inhibitors entered clinical trial.
742	16181138	Most PARP-1 inhibitors mimic the nicotinamide of NAD(+) and the structure-activity relationships are understood in terms of the structure of the catalytic site.
743	16181138	However, five questions remain if PARP-1 inhibitors are to realise their potential in treating human diseases.
744	16181138	Secondly, some potential clinical applications require tissue-selective PARP-1 inhibition; is this possible through pro-drug approaches?
745	16181138	Thirdly, different diseases may require therapeutic PARP-1 inhibition to be either short-term or chronic; are there potential problems associated with chronic inhibition of this DNA-repair process?
746	16181138	Fourthly, PARP-1 is one of at least eighteen isoforms; is isoform-selectivity essential, desirable or even possible?
747	16181138	Fifthly, PARP activity can be inhibited in cells by inhibition of poly(ADP-ribose)-glycohydrolase (PARG); will this be a viable strategy for future drug design?
748	16181138	A major isoform, PARP-1, has been the target for design of inhibitors for over twenty-five years.
749	16181138	Inhibitors of the activity of PARP-1 have been claimed to have applications in the treatment of many disease states, including cancer, haemorrhagic shock, cardiac infarct, stroke, diabetes, inflammation and retroviral infection, but only recently have PARP-1 inhibitors entered clinical trial.
750	16181138	Most PARP-1 inhibitors mimic the nicotinamide of NAD(+) and the structure-activity relationships are understood in terms of the structure of the catalytic site.
751	16181138	However, five questions remain if PARP-1 inhibitors are to realise their potential in treating human diseases.
752	16181138	Secondly, some potential clinical applications require tissue-selective PARP-1 inhibition; is this possible through pro-drug approaches?
753	16181138	Thirdly, different diseases may require therapeutic PARP-1 inhibition to be either short-term or chronic; are there potential problems associated with chronic inhibition of this DNA-repair process?
754	16181138	Fourthly, PARP-1 is one of at least eighteen isoforms; is isoform-selectivity essential, desirable or even possible?
755	16181138	Fifthly, PARP activity can be inhibited in cells by inhibition of poly(ADP-ribose)-glycohydrolase (PARG); will this be a viable strategy for future drug design?
756	16306359	PARP-1 (Western blot analysis) was abundantly expressed in HSC, and its expression was not affected by high glucose or ABA treatment.
757	16504547	Down-regulation of PARP-1, but not of Ku80 or DNA-PKcs', results in higher gene targeting efficiency.
758	16504547	To test this hypothesis, we examined gene targeting frequencies (TF) in DNA-PK(cs), Ku80 and poly(ADP-ribose) polymerase (PARP-1) nullizygous cells.
759	16504547	We observed a 3-fold TF increase in PARP-1 knockout embryonic stem (ES) cells, which is consistent with the predicted role of PARP-1 as a switch between HR and NHEJ.
760	16504547	To a lesser extent, such effect could be reproduced upon chemical inhibition of PARP-1.
761	16504547	Down-regulation of PARP-1, but not of Ku80 or DNA-PKcs', results in higher gene targeting efficiency.
762	16504547	To test this hypothesis, we examined gene targeting frequencies (TF) in DNA-PK(cs), Ku80 and poly(ADP-ribose) polymerase (PARP-1) nullizygous cells.
763	16504547	We observed a 3-fold TF increase in PARP-1 knockout embryonic stem (ES) cells, which is consistent with the predicted role of PARP-1 as a switch between HR and NHEJ.
764	16504547	To a lesser extent, such effect could be reproduced upon chemical inhibition of PARP-1.
765	16504547	Down-regulation of PARP-1, but not of Ku80 or DNA-PKcs', results in higher gene targeting efficiency.
766	16504547	To test this hypothesis, we examined gene targeting frequencies (TF) in DNA-PK(cs), Ku80 and poly(ADP-ribose) polymerase (PARP-1) nullizygous cells.
767	16504547	We observed a 3-fold TF increase in PARP-1 knockout embryonic stem (ES) cells, which is consistent with the predicted role of PARP-1 as a switch between HR and NHEJ.
768	16504547	To a lesser extent, such effect could be reproduced upon chemical inhibition of PARP-1.
769	16504547	Down-regulation of PARP-1, but not of Ku80 or DNA-PKcs', results in higher gene targeting efficiency.
770	16504547	To test this hypothesis, we examined gene targeting frequencies (TF) in DNA-PK(cs), Ku80 and poly(ADP-ribose) polymerase (PARP-1) nullizygous cells.
771	16504547	We observed a 3-fold TF increase in PARP-1 knockout embryonic stem (ES) cells, which is consistent with the predicted role of PARP-1 as a switch between HR and NHEJ.
772	16504547	To a lesser extent, such effect could be reproduced upon chemical inhibition of PARP-1.
773	16505238	MafA expression and insulin promoter activity are induced by nicotinamide and related compounds in INS-1 pancreatic beta-cells.
774	16505238	Exposure of INS-1 beta-cells to elevated glucose leads to reduced insulin gene transcription, and this is associated with diminished binding of pancreatic duodenal homeobox factor 1 (PDX-1) and mammalian homologue of avian MafA/l-Maf (MafA).
775	16505238	Nicotinamide and other low-potency poly(ADP-ribose) polymerase (PARP) inhibitors were thus tested for their ability to restore insulin promoter activity.
776	16505238	The low-potency PARP inhibitors nicotinamide, 3-aminobenzamide, or PD128763 increased expression of a human insulin reporter gene suppressed by elevated glucose.
777	16505238	In contrast, the potent PARP-1 inhibitors PJ34 or INO-1001 had no effect on promoter activity.
778	16505238	Site-directed mutations of the human insulin promoter mapped the low-potency PARP inhibitor response to the C1 element, which serves as a MafA binding site.
779	16505238	Low-potency PARP inhibitors restored MafA mRNA and protein levels, but they had no affect on PDX-1 protein levels or binding activity.
780	16505238	Increased MafA expression by low-potency PARP inhibitors was independent of increased MafA protein or mRNA stability.
781	16505238	These data suggest that low-potency PARP inhibitors increase insulin biosynthesis, in part, through a mechanism involving increased MafA gene transcription.
782	16631535	Aldose reductase inhibition counteracts nitrosative stress and poly(ADP-ribose) polymerase activation in diabetic rat kidney and high-glucose-exposed human mesangial cells.
783	16631535	In vitro studies revealed the presence of both AR and PARP-1 in human mesangial cells, and none of these two variables were affected by high glucose or F treatment.
784	16810332	The inhibition and treatment of breast cancer with poly (ADP-ribose) polymerase (PARP-1) inhibitors.
785	16810332	Recent reports carried out in non-cancerous mouse BRCA1- or BRCA2-deficient embryonic stem (ES) cells, and hamster BRCA2-deficient cells have demonstrated that the targeted inhibition of poly(ADP-ribose) polymerase (PARP-1) kills BRCA mutant cells with high specificity.
786	16810332	Although these studies bring hope for BRCA mutation carriers, the effectiveness of PARP-1 inhibitors for breast cancer remains elusive.
787	16810332	Here we present the first in vivo demonstration of PARP-1 activity in BRCA1-deficient mammary tumors and describe the effects of PARP-1 inhibitors (AG14361, NU1025, and 3-aminobenzamide) on BRCA1-deficient ES cells, mouse and human breast cancer cells.
788	16810332	In human tumor cells, PARP-1 inhibitors showed no difference in vitro in limiting the growth of mammary tumors irrespective of their BRCA1 status.
789	16810332	These results suggest that PARP-1 inhibitors may non-specifically inhibit the growth of mammary tumors.
790	16810332	The inhibition and treatment of breast cancer with poly (ADP-ribose) polymerase (PARP-1) inhibitors.
791	16810332	Recent reports carried out in non-cancerous mouse BRCA1- or BRCA2-deficient embryonic stem (ES) cells, and hamster BRCA2-deficient cells have demonstrated that the targeted inhibition of poly(ADP-ribose) polymerase (PARP-1) kills BRCA mutant cells with high specificity.
792	16810332	Although these studies bring hope for BRCA mutation carriers, the effectiveness of PARP-1 inhibitors for breast cancer remains elusive.
793	16810332	Here we present the first in vivo demonstration of PARP-1 activity in BRCA1-deficient mammary tumors and describe the effects of PARP-1 inhibitors (AG14361, NU1025, and 3-aminobenzamide) on BRCA1-deficient ES cells, mouse and human breast cancer cells.
794	16810332	In human tumor cells, PARP-1 inhibitors showed no difference in vitro in limiting the growth of mammary tumors irrespective of their BRCA1 status.
795	16810332	These results suggest that PARP-1 inhibitors may non-specifically inhibit the growth of mammary tumors.
796	16810332	The inhibition and treatment of breast cancer with poly (ADP-ribose) polymerase (PARP-1) inhibitors.
797	16810332	Recent reports carried out in non-cancerous mouse BRCA1- or BRCA2-deficient embryonic stem (ES) cells, and hamster BRCA2-deficient cells have demonstrated that the targeted inhibition of poly(ADP-ribose) polymerase (PARP-1) kills BRCA mutant cells with high specificity.
798	16810332	Although these studies bring hope for BRCA mutation carriers, the effectiveness of PARP-1 inhibitors for breast cancer remains elusive.
799	16810332	Here we present the first in vivo demonstration of PARP-1 activity in BRCA1-deficient mammary tumors and describe the effects of PARP-1 inhibitors (AG14361, NU1025, and 3-aminobenzamide) on BRCA1-deficient ES cells, mouse and human breast cancer cells.
800	16810332	In human tumor cells, PARP-1 inhibitors showed no difference in vitro in limiting the growth of mammary tumors irrespective of their BRCA1 status.
801	16810332	These results suggest that PARP-1 inhibitors may non-specifically inhibit the growth of mammary tumors.
802	16810332	The inhibition and treatment of breast cancer with poly (ADP-ribose) polymerase (PARP-1) inhibitors.
803	16810332	Recent reports carried out in non-cancerous mouse BRCA1- or BRCA2-deficient embryonic stem (ES) cells, and hamster BRCA2-deficient cells have demonstrated that the targeted inhibition of poly(ADP-ribose) polymerase (PARP-1) kills BRCA mutant cells with high specificity.
804	16810332	Although these studies bring hope for BRCA mutation carriers, the effectiveness of PARP-1 inhibitors for breast cancer remains elusive.
805	16810332	Here we present the first in vivo demonstration of PARP-1 activity in BRCA1-deficient mammary tumors and describe the effects of PARP-1 inhibitors (AG14361, NU1025, and 3-aminobenzamide) on BRCA1-deficient ES cells, mouse and human breast cancer cells.
806	16810332	In human tumor cells, PARP-1 inhibitors showed no difference in vitro in limiting the growth of mammary tumors irrespective of their BRCA1 status.
807	16810332	These results suggest that PARP-1 inhibitors may non-specifically inhibit the growth of mammary tumors.
808	16810332	The inhibition and treatment of breast cancer with poly (ADP-ribose) polymerase (PARP-1) inhibitors.
809	16810332	Recent reports carried out in non-cancerous mouse BRCA1- or BRCA2-deficient embryonic stem (ES) cells, and hamster BRCA2-deficient cells have demonstrated that the targeted inhibition of poly(ADP-ribose) polymerase (PARP-1) kills BRCA mutant cells with high specificity.
810	16810332	Although these studies bring hope for BRCA mutation carriers, the effectiveness of PARP-1 inhibitors for breast cancer remains elusive.
811	16810332	Here we present the first in vivo demonstration of PARP-1 activity in BRCA1-deficient mammary tumors and describe the effects of PARP-1 inhibitors (AG14361, NU1025, and 3-aminobenzamide) on BRCA1-deficient ES cells, mouse and human breast cancer cells.
812	16810332	In human tumor cells, PARP-1 inhibitors showed no difference in vitro in limiting the growth of mammary tumors irrespective of their BRCA1 status.
813	16810332	These results suggest that PARP-1 inhibitors may non-specifically inhibit the growth of mammary tumors.
814	16810332	The inhibition and treatment of breast cancer with poly (ADP-ribose) polymerase (PARP-1) inhibitors.
815	16810332	Recent reports carried out in non-cancerous mouse BRCA1- or BRCA2-deficient embryonic stem (ES) cells, and hamster BRCA2-deficient cells have demonstrated that the targeted inhibition of poly(ADP-ribose) polymerase (PARP-1) kills BRCA mutant cells with high specificity.
816	16810332	Although these studies bring hope for BRCA mutation carriers, the effectiveness of PARP-1 inhibitors for breast cancer remains elusive.
817	16810332	Here we present the first in vivo demonstration of PARP-1 activity in BRCA1-deficient mammary tumors and describe the effects of PARP-1 inhibitors (AG14361, NU1025, and 3-aminobenzamide) on BRCA1-deficient ES cells, mouse and human breast cancer cells.
818	16810332	In human tumor cells, PARP-1 inhibitors showed no difference in vitro in limiting the growth of mammary tumors irrespective of their BRCA1 status.
819	16810332	These results suggest that PARP-1 inhibitors may non-specifically inhibit the growth of mammary tumors.
820	16870158	PARP-1 overactivation and the subsequent extensive turnover of its substrate NAD+ put a large demand on mitochondrial ATP-production.
821	16870158	Furthermore, due to its reported role in NF-kappaB and AP-1 mediated production of pro-inflammatory cytokines, PARP-1 is considered an interesting target in the treatment of these diseases.
822	16870158	In this study the PARP-1 inhibiting capacity of caffeine and several metabolites as well as other (methyl)xanthines was tested using an ELISA-assay with purified human PARP-1.
823	16870158	Caffeine itself showed only weak PARP-1 inhibiting activity, whereas the caffeine metabolites 1,7-dimethylxanthine, 3-methylxanthine and 1-methylxanthine, as well as theobromine and theophylline showed significant PARP-1 inhibiting activity.
824	16870158	Concluding, caffeine metabolites are inhibitors of PARP-1 and the major caffeine metabolite 1,7-dimethylxanthine has significant PARP-1 inhibiting activity in cultured epithelial and endothelial cells at physiological concentrations.
825	16870158	PARP-1 overactivation and the subsequent extensive turnover of its substrate NAD+ put a large demand on mitochondrial ATP-production.
826	16870158	Furthermore, due to its reported role in NF-kappaB and AP-1 mediated production of pro-inflammatory cytokines, PARP-1 is considered an interesting target in the treatment of these diseases.
827	16870158	In this study the PARP-1 inhibiting capacity of caffeine and several metabolites as well as other (methyl)xanthines was tested using an ELISA-assay with purified human PARP-1.
828	16870158	Caffeine itself showed only weak PARP-1 inhibiting activity, whereas the caffeine metabolites 1,7-dimethylxanthine, 3-methylxanthine and 1-methylxanthine, as well as theobromine and theophylline showed significant PARP-1 inhibiting activity.
829	16870158	Concluding, caffeine metabolites are inhibitors of PARP-1 and the major caffeine metabolite 1,7-dimethylxanthine has significant PARP-1 inhibiting activity in cultured epithelial and endothelial cells at physiological concentrations.
830	16870158	PARP-1 overactivation and the subsequent extensive turnover of its substrate NAD+ put a large demand on mitochondrial ATP-production.
831	16870158	Furthermore, due to its reported role in NF-kappaB and AP-1 mediated production of pro-inflammatory cytokines, PARP-1 is considered an interesting target in the treatment of these diseases.
832	16870158	In this study the PARP-1 inhibiting capacity of caffeine and several metabolites as well as other (methyl)xanthines was tested using an ELISA-assay with purified human PARP-1.
833	16870158	Caffeine itself showed only weak PARP-1 inhibiting activity, whereas the caffeine metabolites 1,7-dimethylxanthine, 3-methylxanthine and 1-methylxanthine, as well as theobromine and theophylline showed significant PARP-1 inhibiting activity.
834	16870158	Concluding, caffeine metabolites are inhibitors of PARP-1 and the major caffeine metabolite 1,7-dimethylxanthine has significant PARP-1 inhibiting activity in cultured epithelial and endothelial cells at physiological concentrations.
835	16870158	PARP-1 overactivation and the subsequent extensive turnover of its substrate NAD+ put a large demand on mitochondrial ATP-production.
836	16870158	Furthermore, due to its reported role in NF-kappaB and AP-1 mediated production of pro-inflammatory cytokines, PARP-1 is considered an interesting target in the treatment of these diseases.
837	16870158	In this study the PARP-1 inhibiting capacity of caffeine and several metabolites as well as other (methyl)xanthines was tested using an ELISA-assay with purified human PARP-1.
838	16870158	Caffeine itself showed only weak PARP-1 inhibiting activity, whereas the caffeine metabolites 1,7-dimethylxanthine, 3-methylxanthine and 1-methylxanthine, as well as theobromine and theophylline showed significant PARP-1 inhibiting activity.
839	16870158	Concluding, caffeine metabolites are inhibitors of PARP-1 and the major caffeine metabolite 1,7-dimethylxanthine has significant PARP-1 inhibiting activity in cultured epithelial and endothelial cells at physiological concentrations.
840	16870158	PARP-1 overactivation and the subsequent extensive turnover of its substrate NAD+ put a large demand on mitochondrial ATP-production.
841	16870158	Furthermore, due to its reported role in NF-kappaB and AP-1 mediated production of pro-inflammatory cytokines, PARP-1 is considered an interesting target in the treatment of these diseases.
842	16870158	In this study the PARP-1 inhibiting capacity of caffeine and several metabolites as well as other (methyl)xanthines was tested using an ELISA-assay with purified human PARP-1.
843	16870158	Caffeine itself showed only weak PARP-1 inhibiting activity, whereas the caffeine metabolites 1,7-dimethylxanthine, 3-methylxanthine and 1-methylxanthine, as well as theobromine and theophylline showed significant PARP-1 inhibiting activity.
844	16870158	Concluding, caffeine metabolites are inhibitors of PARP-1 and the major caffeine metabolite 1,7-dimethylxanthine has significant PARP-1 inhibiting activity in cultured epithelial and endothelial cells at physiological concentrations.
845	16906222	PARP-1 inhibitors: are they the long-sought genetically specific drugs for BRCA1/2-associated breast cancers?
846	16906222	Recent studies demonstrated that PARP-1 [poly(ADP-ribose) polymerase-1] inhibitors kill breast cancer associated gene-1 and -2 (BRCA1/2) deficient cells with extremely high efficiency while BRCA+/- and BRCA+/+ cells are relatively non-responsive to the treatment.
847	16906222	It was therefore proposed that PARP-1 inhibitors might be the long-sought genetically specific drugs that are both safe and effective for treating BRCA1/2-associated breast cancers.
848	16906222	However, a report published in a recent issue of the International Journal of Biological Sciences revealed that PARP-1 inhibitors, although able to kill naïve BRCA1 mutant cells with high specificity both in vitro and in vivo, exhibit minimal specificity in inhibiting the growth of mouse mammary tumor cells irrespective of their BRCA1 status in allograft nude mice.
849	16906222	Non-specific inhibition in human BRCA1+/+, BRCA1+/-, and BRCA1-/- breast cancer cells by PARP-1 inhibitors was also observed.
850	16906222	Additional mutations occurring during cancer progression may be a culprit, although the exact cause for the resistance of BRCA1-/- breast cancer cells to PARP-1 inhibitors remains elusive.
851	16906222	PARP-1 inhibitors: are they the long-sought genetically specific drugs for BRCA1/2-associated breast cancers?
852	16906222	Recent studies demonstrated that PARP-1 [poly(ADP-ribose) polymerase-1] inhibitors kill breast cancer associated gene-1 and -2 (BRCA1/2) deficient cells with extremely high efficiency while BRCA+/- and BRCA+/+ cells are relatively non-responsive to the treatment.
853	16906222	It was therefore proposed that PARP-1 inhibitors might be the long-sought genetically specific drugs that are both safe and effective for treating BRCA1/2-associated breast cancers.
854	16906222	However, a report published in a recent issue of the International Journal of Biological Sciences revealed that PARP-1 inhibitors, although able to kill naïve BRCA1 mutant cells with high specificity both in vitro and in vivo, exhibit minimal specificity in inhibiting the growth of mouse mammary tumor cells irrespective of their BRCA1 status in allograft nude mice.
855	16906222	Non-specific inhibition in human BRCA1+/+, BRCA1+/-, and BRCA1-/- breast cancer cells by PARP-1 inhibitors was also observed.
856	16906222	Additional mutations occurring during cancer progression may be a culprit, although the exact cause for the resistance of BRCA1-/- breast cancer cells to PARP-1 inhibitors remains elusive.
857	16906222	PARP-1 inhibitors: are they the long-sought genetically specific drugs for BRCA1/2-associated breast cancers?
858	16906222	Recent studies demonstrated that PARP-1 [poly(ADP-ribose) polymerase-1] inhibitors kill breast cancer associated gene-1 and -2 (BRCA1/2) deficient cells with extremely high efficiency while BRCA+/- and BRCA+/+ cells are relatively non-responsive to the treatment.
859	16906222	It was therefore proposed that PARP-1 inhibitors might be the long-sought genetically specific drugs that are both safe and effective for treating BRCA1/2-associated breast cancers.
860	16906222	However, a report published in a recent issue of the International Journal of Biological Sciences revealed that PARP-1 inhibitors, although able to kill naïve BRCA1 mutant cells with high specificity both in vitro and in vivo, exhibit minimal specificity in inhibiting the growth of mouse mammary tumor cells irrespective of their BRCA1 status in allograft nude mice.
861	16906222	Non-specific inhibition in human BRCA1+/+, BRCA1+/-, and BRCA1-/- breast cancer cells by PARP-1 inhibitors was also observed.
862	16906222	Additional mutations occurring during cancer progression may be a culprit, although the exact cause for the resistance of BRCA1-/- breast cancer cells to PARP-1 inhibitors remains elusive.
863	16906222	PARP-1 inhibitors: are they the long-sought genetically specific drugs for BRCA1/2-associated breast cancers?
864	16906222	Recent studies demonstrated that PARP-1 [poly(ADP-ribose) polymerase-1] inhibitors kill breast cancer associated gene-1 and -2 (BRCA1/2) deficient cells with extremely high efficiency while BRCA+/- and BRCA+/+ cells are relatively non-responsive to the treatment.
865	16906222	It was therefore proposed that PARP-1 inhibitors might be the long-sought genetically specific drugs that are both safe and effective for treating BRCA1/2-associated breast cancers.
866	16906222	However, a report published in a recent issue of the International Journal of Biological Sciences revealed that PARP-1 inhibitors, although able to kill naïve BRCA1 mutant cells with high specificity both in vitro and in vivo, exhibit minimal specificity in inhibiting the growth of mouse mammary tumor cells irrespective of their BRCA1 status in allograft nude mice.
867	16906222	Non-specific inhibition in human BRCA1+/+, BRCA1+/-, and BRCA1-/- breast cancer cells by PARP-1 inhibitors was also observed.
868	16906222	Additional mutations occurring during cancer progression may be a culprit, although the exact cause for the resistance of BRCA1-/- breast cancer cells to PARP-1 inhibitors remains elusive.
869	16906222	PARP-1 inhibitors: are they the long-sought genetically specific drugs for BRCA1/2-associated breast cancers?
870	16906222	Recent studies demonstrated that PARP-1 [poly(ADP-ribose) polymerase-1] inhibitors kill breast cancer associated gene-1 and -2 (BRCA1/2) deficient cells with extremely high efficiency while BRCA+/- and BRCA+/+ cells are relatively non-responsive to the treatment.
871	16906222	It was therefore proposed that PARP-1 inhibitors might be the long-sought genetically specific drugs that are both safe and effective for treating BRCA1/2-associated breast cancers.
872	16906222	However, a report published in a recent issue of the International Journal of Biological Sciences revealed that PARP-1 inhibitors, although able to kill naïve BRCA1 mutant cells with high specificity both in vitro and in vivo, exhibit minimal specificity in inhibiting the growth of mouse mammary tumor cells irrespective of their BRCA1 status in allograft nude mice.
873	16906222	Non-specific inhibition in human BRCA1+/+, BRCA1+/-, and BRCA1-/- breast cancer cells by PARP-1 inhibitors was also observed.
874	16906222	Additional mutations occurring during cancer progression may be a culprit, although the exact cause for the resistance of BRCA1-/- breast cancer cells to PARP-1 inhibitors remains elusive.
875	16906222	PARP-1 inhibitors: are they the long-sought genetically specific drugs for BRCA1/2-associated breast cancers?
876	16906222	Recent studies demonstrated that PARP-1 [poly(ADP-ribose) polymerase-1] inhibitors kill breast cancer associated gene-1 and -2 (BRCA1/2) deficient cells with extremely high efficiency while BRCA+/- and BRCA+/+ cells are relatively non-responsive to the treatment.
877	16906222	It was therefore proposed that PARP-1 inhibitors might be the long-sought genetically specific drugs that are both safe and effective for treating BRCA1/2-associated breast cancers.
878	16906222	However, a report published in a recent issue of the International Journal of Biological Sciences revealed that PARP-1 inhibitors, although able to kill naïve BRCA1 mutant cells with high specificity both in vitro and in vivo, exhibit minimal specificity in inhibiting the growth of mouse mammary tumor cells irrespective of their BRCA1 status in allograft nude mice.
879	16906222	Non-specific inhibition in human BRCA1+/+, BRCA1+/-, and BRCA1-/- breast cancer cells by PARP-1 inhibitors was also observed.
880	16906222	Additional mutations occurring during cancer progression may be a culprit, although the exact cause for the resistance of BRCA1-/- breast cancer cells to PARP-1 inhibitors remains elusive.
881	17318223	Haploinsufficiency of Parp1 accelerates Brca1-associated centrosome amplification, telomere shortening, genetic instability, apoptosis, and embryonic lethality.
882	17318223	The breast tumor associated gene-1 (BRCA1) and poly(ADP-ribose) polymerase-1 (PARP1) are both involved in DNA-damage response and DNA-damage repair.
883	17318223	Recent investigations have suggested that inhibition of PARP1 represents a promising chemopreventive/therapeutic approach for specifically treating BRCA1- and BRCA2-associated breast cancer.
884	17318223	However, studies in mouse models reveal that Parp1-null mutation results in genetic instability and mammary tumor formation, casting significant doubt on the safety of PARP1 inhibition as a therapy for the breast cancer.
885	17318223	To study the genetic interactions between Brca1 and Parp1, we interbred mice carrying a heterozygous deletion of full-length Brca1 (Brca1(+/Delta11)) with Parp1-null mice.
886	17318223	We show that Brca1(Delta11/Delta11);Parp1(-/-) embryos die before embryonic (E) day 6.5, whereas Brca1(Delta11/Delta11) embryos die after E12.5, indicating that absence of Parp1 dramatically accelerates lethality caused by Brca1 deficiency.
887	17318223	Surprisingly, haploinsufficiency of Parp1 in Brca1(Delta11/Delta11) embryos induces a severe chromosome aberrations, centrosome amplification, and telomere dysfunction, leading to apoptosis and accelerated embryonic lethality.
888	17318223	Notably, telomere shortening in Brca1(Delta11/Delta11);Parp1(+/-) MEFs was correlated with decreased expression of Ku70, which plays an important role in telomere maintenance.
889	17318223	Thus, haploid loss of Parp1 is sufficient to induce lethality of Brca1-deficient cells, suggesting that partial inhibition of PARP1 may represent a practical chemopreventive/therapeutic approach for BRCA1-associated breast cancer.
890	17318223	Haploinsufficiency of Parp1 accelerates Brca1-associated centrosome amplification, telomere shortening, genetic instability, apoptosis, and embryonic lethality.
891	17318223	The breast tumor associated gene-1 (BRCA1) and poly(ADP-ribose) polymerase-1 (PARP1) are both involved in DNA-damage response and DNA-damage repair.
892	17318223	Recent investigations have suggested that inhibition of PARP1 represents a promising chemopreventive/therapeutic approach for specifically treating BRCA1- and BRCA2-associated breast cancer.
893	17318223	However, studies in mouse models reveal that Parp1-null mutation results in genetic instability and mammary tumor formation, casting significant doubt on the safety of PARP1 inhibition as a therapy for the breast cancer.
894	17318223	To study the genetic interactions between Brca1 and Parp1, we interbred mice carrying a heterozygous deletion of full-length Brca1 (Brca1(+/Delta11)) with Parp1-null mice.
895	17318223	We show that Brca1(Delta11/Delta11);Parp1(-/-) embryos die before embryonic (E) day 6.5, whereas Brca1(Delta11/Delta11) embryos die after E12.5, indicating that absence of Parp1 dramatically accelerates lethality caused by Brca1 deficiency.
896	17318223	Surprisingly, haploinsufficiency of Parp1 in Brca1(Delta11/Delta11) embryos induces a severe chromosome aberrations, centrosome amplification, and telomere dysfunction, leading to apoptosis and accelerated embryonic lethality.
897	17318223	Notably, telomere shortening in Brca1(Delta11/Delta11);Parp1(+/-) MEFs was correlated with decreased expression of Ku70, which plays an important role in telomere maintenance.
898	17318223	Thus, haploid loss of Parp1 is sufficient to induce lethality of Brca1-deficient cells, suggesting that partial inhibition of PARP1 may represent a practical chemopreventive/therapeutic approach for BRCA1-associated breast cancer.
899	17318223	Haploinsufficiency of Parp1 accelerates Brca1-associated centrosome amplification, telomere shortening, genetic instability, apoptosis, and embryonic lethality.
900	17318223	The breast tumor associated gene-1 (BRCA1) and poly(ADP-ribose) polymerase-1 (PARP1) are both involved in DNA-damage response and DNA-damage repair.
901	17318223	Recent investigations have suggested that inhibition of PARP1 represents a promising chemopreventive/therapeutic approach for specifically treating BRCA1- and BRCA2-associated breast cancer.
902	17318223	However, studies in mouse models reveal that Parp1-null mutation results in genetic instability and mammary tumor formation, casting significant doubt on the safety of PARP1 inhibition as a therapy for the breast cancer.
903	17318223	To study the genetic interactions between Brca1 and Parp1, we interbred mice carrying a heterozygous deletion of full-length Brca1 (Brca1(+/Delta11)) with Parp1-null mice.
904	17318223	We show that Brca1(Delta11/Delta11);Parp1(-/-) embryos die before embryonic (E) day 6.5, whereas Brca1(Delta11/Delta11) embryos die after E12.5, indicating that absence of Parp1 dramatically accelerates lethality caused by Brca1 deficiency.
905	17318223	Surprisingly, haploinsufficiency of Parp1 in Brca1(Delta11/Delta11) embryos induces a severe chromosome aberrations, centrosome amplification, and telomere dysfunction, leading to apoptosis and accelerated embryonic lethality.
906	17318223	Notably, telomere shortening in Brca1(Delta11/Delta11);Parp1(+/-) MEFs was correlated with decreased expression of Ku70, which plays an important role in telomere maintenance.
907	17318223	Thus, haploid loss of Parp1 is sufficient to induce lethality of Brca1-deficient cells, suggesting that partial inhibition of PARP1 may represent a practical chemopreventive/therapeutic approach for BRCA1-associated breast cancer.
908	17318223	Haploinsufficiency of Parp1 accelerates Brca1-associated centrosome amplification, telomere shortening, genetic instability, apoptosis, and embryonic lethality.
909	17318223	The breast tumor associated gene-1 (BRCA1) and poly(ADP-ribose) polymerase-1 (PARP1) are both involved in DNA-damage response and DNA-damage repair.
910	17318223	Recent investigations have suggested that inhibition of PARP1 represents a promising chemopreventive/therapeutic approach for specifically treating BRCA1- and BRCA2-associated breast cancer.
911	17318223	However, studies in mouse models reveal that Parp1-null mutation results in genetic instability and mammary tumor formation, casting significant doubt on the safety of PARP1 inhibition as a therapy for the breast cancer.
912	17318223	To study the genetic interactions between Brca1 and Parp1, we interbred mice carrying a heterozygous deletion of full-length Brca1 (Brca1(+/Delta11)) with Parp1-null mice.
913	17318223	We show that Brca1(Delta11/Delta11);Parp1(-/-) embryos die before embryonic (E) day 6.5, whereas Brca1(Delta11/Delta11) embryos die after E12.5, indicating that absence of Parp1 dramatically accelerates lethality caused by Brca1 deficiency.
914	17318223	Surprisingly, haploinsufficiency of Parp1 in Brca1(Delta11/Delta11) embryos induces a severe chromosome aberrations, centrosome amplification, and telomere dysfunction, leading to apoptosis and accelerated embryonic lethality.
915	17318223	Notably, telomere shortening in Brca1(Delta11/Delta11);Parp1(+/-) MEFs was correlated with decreased expression of Ku70, which plays an important role in telomere maintenance.
916	17318223	Thus, haploid loss of Parp1 is sufficient to induce lethality of Brca1-deficient cells, suggesting that partial inhibition of PARP1 may represent a practical chemopreventive/therapeutic approach for BRCA1-associated breast cancer.
917	17318223	Haploinsufficiency of Parp1 accelerates Brca1-associated centrosome amplification, telomere shortening, genetic instability, apoptosis, and embryonic lethality.
918	17318223	The breast tumor associated gene-1 (BRCA1) and poly(ADP-ribose) polymerase-1 (PARP1) are both involved in DNA-damage response and DNA-damage repair.
919	17318223	Recent investigations have suggested that inhibition of PARP1 represents a promising chemopreventive/therapeutic approach for specifically treating BRCA1- and BRCA2-associated breast cancer.
920	17318223	However, studies in mouse models reveal that Parp1-null mutation results in genetic instability and mammary tumor formation, casting significant doubt on the safety of PARP1 inhibition as a therapy for the breast cancer.
921	17318223	To study the genetic interactions between Brca1 and Parp1, we interbred mice carrying a heterozygous deletion of full-length Brca1 (Brca1(+/Delta11)) with Parp1-null mice.
922	17318223	We show that Brca1(Delta11/Delta11);Parp1(-/-) embryos die before embryonic (E) day 6.5, whereas Brca1(Delta11/Delta11) embryos die after E12.5, indicating that absence of Parp1 dramatically accelerates lethality caused by Brca1 deficiency.
923	17318223	Surprisingly, haploinsufficiency of Parp1 in Brca1(Delta11/Delta11) embryos induces a severe chromosome aberrations, centrosome amplification, and telomere dysfunction, leading to apoptosis and accelerated embryonic lethality.
924	17318223	Notably, telomere shortening in Brca1(Delta11/Delta11);Parp1(+/-) MEFs was correlated with decreased expression of Ku70, which plays an important role in telomere maintenance.
925	17318223	Thus, haploid loss of Parp1 is sufficient to induce lethality of Brca1-deficient cells, suggesting that partial inhibition of PARP1 may represent a practical chemopreventive/therapeutic approach for BRCA1-associated breast cancer.
926	17318223	Haploinsufficiency of Parp1 accelerates Brca1-associated centrosome amplification, telomere shortening, genetic instability, apoptosis, and embryonic lethality.
927	17318223	The breast tumor associated gene-1 (BRCA1) and poly(ADP-ribose) polymerase-1 (PARP1) are both involved in DNA-damage response and DNA-damage repair.
928	17318223	Recent investigations have suggested that inhibition of PARP1 represents a promising chemopreventive/therapeutic approach for specifically treating BRCA1- and BRCA2-associated breast cancer.
929	17318223	However, studies in mouse models reveal that Parp1-null mutation results in genetic instability and mammary tumor formation, casting significant doubt on the safety of PARP1 inhibition as a therapy for the breast cancer.
930	17318223	To study the genetic interactions between Brca1 and Parp1, we interbred mice carrying a heterozygous deletion of full-length Brca1 (Brca1(+/Delta11)) with Parp1-null mice.
931	17318223	We show that Brca1(Delta11/Delta11);Parp1(-/-) embryos die before embryonic (E) day 6.5, whereas Brca1(Delta11/Delta11) embryos die after E12.5, indicating that absence of Parp1 dramatically accelerates lethality caused by Brca1 deficiency.
932	17318223	Surprisingly, haploinsufficiency of Parp1 in Brca1(Delta11/Delta11) embryos induces a severe chromosome aberrations, centrosome amplification, and telomere dysfunction, leading to apoptosis and accelerated embryonic lethality.
933	17318223	Notably, telomere shortening in Brca1(Delta11/Delta11);Parp1(+/-) MEFs was correlated with decreased expression of Ku70, which plays an important role in telomere maintenance.
934	17318223	Thus, haploid loss of Parp1 is sufficient to induce lethality of Brca1-deficient cells, suggesting that partial inhibition of PARP1 may represent a practical chemopreventive/therapeutic approach for BRCA1-associated breast cancer.
935	17318223	Haploinsufficiency of Parp1 accelerates Brca1-associated centrosome amplification, telomere shortening, genetic instability, apoptosis, and embryonic lethality.
936	17318223	The breast tumor associated gene-1 (BRCA1) and poly(ADP-ribose) polymerase-1 (PARP1) are both involved in DNA-damage response and DNA-damage repair.
937	17318223	Recent investigations have suggested that inhibition of PARP1 represents a promising chemopreventive/therapeutic approach for specifically treating BRCA1- and BRCA2-associated breast cancer.
938	17318223	However, studies in mouse models reveal that Parp1-null mutation results in genetic instability and mammary tumor formation, casting significant doubt on the safety of PARP1 inhibition as a therapy for the breast cancer.
939	17318223	To study the genetic interactions between Brca1 and Parp1, we interbred mice carrying a heterozygous deletion of full-length Brca1 (Brca1(+/Delta11)) with Parp1-null mice.
940	17318223	We show that Brca1(Delta11/Delta11);Parp1(-/-) embryos die before embryonic (E) day 6.5, whereas Brca1(Delta11/Delta11) embryos die after E12.5, indicating that absence of Parp1 dramatically accelerates lethality caused by Brca1 deficiency.
941	17318223	Surprisingly, haploinsufficiency of Parp1 in Brca1(Delta11/Delta11) embryos induces a severe chromosome aberrations, centrosome amplification, and telomere dysfunction, leading to apoptosis and accelerated embryonic lethality.
942	17318223	Notably, telomere shortening in Brca1(Delta11/Delta11);Parp1(+/-) MEFs was correlated with decreased expression of Ku70, which plays an important role in telomere maintenance.
943	17318223	Thus, haploid loss of Parp1 is sufficient to induce lethality of Brca1-deficient cells, suggesting that partial inhibition of PARP1 may represent a practical chemopreventive/therapeutic approach for BRCA1-associated breast cancer.
944	17318223	Haploinsufficiency of Parp1 accelerates Brca1-associated centrosome amplification, telomere shortening, genetic instability, apoptosis, and embryonic lethality.
945	17318223	The breast tumor associated gene-1 (BRCA1) and poly(ADP-ribose) polymerase-1 (PARP1) are both involved in DNA-damage response and DNA-damage repair.
946	17318223	Recent investigations have suggested that inhibition of PARP1 represents a promising chemopreventive/therapeutic approach for specifically treating BRCA1- and BRCA2-associated breast cancer.
947	17318223	However, studies in mouse models reveal that Parp1-null mutation results in genetic instability and mammary tumor formation, casting significant doubt on the safety of PARP1 inhibition as a therapy for the breast cancer.
948	17318223	To study the genetic interactions between Brca1 and Parp1, we interbred mice carrying a heterozygous deletion of full-length Brca1 (Brca1(+/Delta11)) with Parp1-null mice.
949	17318223	We show that Brca1(Delta11/Delta11);Parp1(-/-) embryos die before embryonic (E) day 6.5, whereas Brca1(Delta11/Delta11) embryos die after E12.5, indicating that absence of Parp1 dramatically accelerates lethality caused by Brca1 deficiency.
950	17318223	Surprisingly, haploinsufficiency of Parp1 in Brca1(Delta11/Delta11) embryos induces a severe chromosome aberrations, centrosome amplification, and telomere dysfunction, leading to apoptosis and accelerated embryonic lethality.
951	17318223	Notably, telomere shortening in Brca1(Delta11/Delta11);Parp1(+/-) MEFs was correlated with decreased expression of Ku70, which plays an important role in telomere maintenance.
952	17318223	Thus, haploid loss of Parp1 is sufficient to induce lethality of Brca1-deficient cells, suggesting that partial inhibition of PARP1 may represent a practical chemopreventive/therapeutic approach for BRCA1-associated breast cancer.
953	17430113	Immunomodulatory factors including IFNgamma, TNFalpha, IL-1, and LPS use IDO induction in responsive antigen presenting cells (APCs) also to transmit tolerogenic signals to T cells.
954	17430113	The importance of IDO dysregulation manifest as autoimmune pellagric dementia is genetically illustrated for Nasu-Hakola Disease (or PLOSL), which is caused by a mutation in the IDO antagonizing genes TYROBP/DAP12 or TREM2.
955	17430113	Chronic elevation of TNFalpha leading to necrotic events by NAD depletion in autoimmune disease likely occurs via combination of persistent IDO activation and iNOS-peroxynitrate activation of PARP1 both of which deplete NAD.
956	17430113	Distinct among the NAD precursors, nicotinic acid specifically activates the g-protein coupled receptor (GPCR) GPR109a to produce the IDO-inducing tolerogenic prostaglandins PGE(2) and PGD(2).
957	17430113	Next, PGD(2) is converted to the anti-inflammatory prostaglandin, 15d-PGJ(2).
958	17430113	These prostaglandins exert potent anti-inflammatory activities through endogenous signaling mechanisms involving the GPCRs EP2, EP4, and DP1 along with PPARgamma respectively.
959	17430113	Alternatively the direct targeting of the non-redox NAD-dependent proteins using resveratrol to activate SIRT1 or PJ34 in order to inhibit PARP1 and prevent autoimmune pathogenesis are also given consideration.
960	17430113	Immunomodulatory factors including IFNgamma, TNFalpha, IL-1, and LPS use IDO induction in responsive antigen presenting cells (APCs) also to transmit tolerogenic signals to T cells.
961	17430113	The importance of IDO dysregulation manifest as autoimmune pellagric dementia is genetically illustrated for Nasu-Hakola Disease (or PLOSL), which is caused by a mutation in the IDO antagonizing genes TYROBP/DAP12 or TREM2.
962	17430113	Chronic elevation of TNFalpha leading to necrotic events by NAD depletion in autoimmune disease likely occurs via combination of persistent IDO activation and iNOS-peroxynitrate activation of PARP1 both of which deplete NAD.
963	17430113	Distinct among the NAD precursors, nicotinic acid specifically activates the g-protein coupled receptor (GPCR) GPR109a to produce the IDO-inducing tolerogenic prostaglandins PGE(2) and PGD(2).
964	17430113	Next, PGD(2) is converted to the anti-inflammatory prostaglandin, 15d-PGJ(2).
965	17430113	These prostaglandins exert potent anti-inflammatory activities through endogenous signaling mechanisms involving the GPCRs EP2, EP4, and DP1 along with PPARgamma respectively.
966	17430113	Alternatively the direct targeting of the non-redox NAD-dependent proteins using resveratrol to activate SIRT1 or PJ34 in order to inhibit PARP1 and prevent autoimmune pathogenesis are also given consideration.
967	17430191	To date, seven isoforms have been identified: PARP-1, PARP-2, PARP-3, PARP-4 (Vault-PARP), PARP-5 (Tankyrases), PARP-7 and PARP-10 with structural domains and different functions.
968	17430191	PARP-1, the best characterised member, works as a DNA damage nick-sensor protein that uses beta-NAD(+) to form polymers of ADP-ribose and has been implicated in DNA repair, maintenance of genomic integrity and mammalian longevity.
969	17430191	To date, seven isoforms have been identified: PARP-1, PARP-2, PARP-3, PARP-4 (Vault-PARP), PARP-5 (Tankyrases), PARP-7 and PARP-10 with structural domains and different functions.
970	17430191	PARP-1, the best characterised member, works as a DNA damage nick-sensor protein that uses beta-NAD(+) to form polymers of ADP-ribose and has been implicated in DNA repair, maintenance of genomic integrity and mammalian longevity.
971	17520094	Poly(ADP-ribose) polymerase-1 (PARP-1) is a member of the PARP enzyme family consisting of PARP-1 and four additional, recently identified poly(ADP-ribosylating) enzymes.
972	17520094	PARP-1 is one of the most abundant nuclear proteins and functions as a DNA nick sensor enzyme.
973	17520094	Poly(ADP-ribose) polymerase-1 (PARP-1) is a member of the PARP enzyme family consisting of PARP-1 and four additional, recently identified poly(ADP-ribosylating) enzymes.
974	17520094	PARP-1 is one of the most abundant nuclear proteins and functions as a DNA nick sensor enzyme.
975	17643414	Flavone as PARP-1 inhibitor: its effect on lipopolysaccharide induced gene-expression.
976	17643414	The nuclear enzyme poly(ADP-ribose) polymerase-1 (PARP-1) which was initially known for its role in the repair of oxidative stress-induced DNA damage, has also been reported to play a mediating role in the inflammatory response.
977	17643414	Studies with PARP-1 knockout models have shown that PARP-1 is a co-activator of Nuclear Factor-kappa B (NF-kappaB), although this appears not to require its enzyme activity.
978	17643414	In addition, drug-induced inhibition of the enzyme activity of PARP-1 was observed to reduce the production of pro-inflammatory mediators.
979	17643414	In this study, the flavonoid compound flavone was demonstrated to significantly inhibit the enzyme activity of PARP-1.
980	17643414	PARP-1 inhibition could have beneficial effects in such diseases as Chronic Obstructive Pulmonary Disease (COPD) and diabetes, by preservation of cellular NAD(+) levels and attenuating inflammatory conditions.
981	17643414	Flavone as PARP-1 inhibitor: its effect on lipopolysaccharide induced gene-expression.
982	17643414	The nuclear enzyme poly(ADP-ribose) polymerase-1 (PARP-1) which was initially known for its role in the repair of oxidative stress-induced DNA damage, has also been reported to play a mediating role in the inflammatory response.
983	17643414	Studies with PARP-1 knockout models have shown that PARP-1 is a co-activator of Nuclear Factor-kappa B (NF-kappaB), although this appears not to require its enzyme activity.
984	17643414	In addition, drug-induced inhibition of the enzyme activity of PARP-1 was observed to reduce the production of pro-inflammatory mediators.
985	17643414	In this study, the flavonoid compound flavone was demonstrated to significantly inhibit the enzyme activity of PARP-1.
986	17643414	PARP-1 inhibition could have beneficial effects in such diseases as Chronic Obstructive Pulmonary Disease (COPD) and diabetes, by preservation of cellular NAD(+) levels and attenuating inflammatory conditions.
987	17643414	Flavone as PARP-1 inhibitor: its effect on lipopolysaccharide induced gene-expression.
988	17643414	The nuclear enzyme poly(ADP-ribose) polymerase-1 (PARP-1) which was initially known for its role in the repair of oxidative stress-induced DNA damage, has also been reported to play a mediating role in the inflammatory response.
989	17643414	Studies with PARP-1 knockout models have shown that PARP-1 is a co-activator of Nuclear Factor-kappa B (NF-kappaB), although this appears not to require its enzyme activity.
990	17643414	In addition, drug-induced inhibition of the enzyme activity of PARP-1 was observed to reduce the production of pro-inflammatory mediators.
991	17643414	In this study, the flavonoid compound flavone was demonstrated to significantly inhibit the enzyme activity of PARP-1.
992	17643414	PARP-1 inhibition could have beneficial effects in such diseases as Chronic Obstructive Pulmonary Disease (COPD) and diabetes, by preservation of cellular NAD(+) levels and attenuating inflammatory conditions.
993	17643414	Flavone as PARP-1 inhibitor: its effect on lipopolysaccharide induced gene-expression.
994	17643414	The nuclear enzyme poly(ADP-ribose) polymerase-1 (PARP-1) which was initially known for its role in the repair of oxidative stress-induced DNA damage, has also been reported to play a mediating role in the inflammatory response.
995	17643414	Studies with PARP-1 knockout models have shown that PARP-1 is a co-activator of Nuclear Factor-kappa B (NF-kappaB), although this appears not to require its enzyme activity.
996	17643414	In addition, drug-induced inhibition of the enzyme activity of PARP-1 was observed to reduce the production of pro-inflammatory mediators.
997	17643414	In this study, the flavonoid compound flavone was demonstrated to significantly inhibit the enzyme activity of PARP-1.
998	17643414	PARP-1 inhibition could have beneficial effects in such diseases as Chronic Obstructive Pulmonary Disease (COPD) and diabetes, by preservation of cellular NAD(+) levels and attenuating inflammatory conditions.
999	17643414	Flavone as PARP-1 inhibitor: its effect on lipopolysaccharide induced gene-expression.
1000	17643414	The nuclear enzyme poly(ADP-ribose) polymerase-1 (PARP-1) which was initially known for its role in the repair of oxidative stress-induced DNA damage, has also been reported to play a mediating role in the inflammatory response.
1001	17643414	Studies with PARP-1 knockout models have shown that PARP-1 is a co-activator of Nuclear Factor-kappa B (NF-kappaB), although this appears not to require its enzyme activity.
1002	17643414	In addition, drug-induced inhibition of the enzyme activity of PARP-1 was observed to reduce the production of pro-inflammatory mediators.
1003	17643414	In this study, the flavonoid compound flavone was demonstrated to significantly inhibit the enzyme activity of PARP-1.
1004	17643414	PARP-1 inhibition could have beneficial effects in such diseases as Chronic Obstructive Pulmonary Disease (COPD) and diabetes, by preservation of cellular NAD(+) levels and attenuating inflammatory conditions.
1005	17643414	Flavone as PARP-1 inhibitor: its effect on lipopolysaccharide induced gene-expression.
1006	17643414	The nuclear enzyme poly(ADP-ribose) polymerase-1 (PARP-1) which was initially known for its role in the repair of oxidative stress-induced DNA damage, has also been reported to play a mediating role in the inflammatory response.
1007	17643414	Studies with PARP-1 knockout models have shown that PARP-1 is a co-activator of Nuclear Factor-kappa B (NF-kappaB), although this appears not to require its enzyme activity.
1008	17643414	In addition, drug-induced inhibition of the enzyme activity of PARP-1 was observed to reduce the production of pro-inflammatory mediators.
1009	17643414	In this study, the flavonoid compound flavone was demonstrated to significantly inhibit the enzyme activity of PARP-1.
1010	17643414	PARP-1 inhibition could have beneficial effects in such diseases as Chronic Obstructive Pulmonary Disease (COPD) and diabetes, by preservation of cellular NAD(+) levels and attenuating inflammatory conditions.
1011	18657544	PARP-1 knockout (PARP(-/-)) mice and their respective controls were fed a 30% galactose diet while male Sprague-Dawley rats were injected with streptozotocin and subsequently treated with PARP inhibitor 3-aminobenzamide (ABA).
1012	18657544	This study has elucidated for the first time a PARP-dependent, p300-associated pathway mediating the development of structural alterations in the diabetic heart.
1013	19076445	Poly(ADP-ribose) polymerase-1 (PARP-1) is an abundant nuclear protein best known to facilitate DNA base excision repair.
1014	19076445	Recent work has expanded the physiologic functions of PARP-1, and it is clear that the full range of biologic actions of this important protein are not yet fully understood.
1015	19076445	Regulation of the product of PARP-1, poly(ADP-ribose) (PAR), is a dynamic process with PAR glycohydrolase playing the major role in the degradation of the polymer.
1016	19076445	Under pathophysiologic situations overactivation of PARP-1 results in unregulated PAR synthesis and widespread neuronal cell death.
1017	19076445	Once thought to be necrotic cell death resulting from energy failure, we have found that PARP-1-dependent cell death is dependent on the generation of PAR, which triggers the nuclear translocation of apoptosis-inducing factor resulting in caspase-independent cell death.
1018	19076445	PARP-1-dependent cell death has been implicated in tissues throughout the body and in diseases afflicting hundreds of millions worldwide, including stroke, Parkinson's disease, heart attack, diabetes, and ischemia reperfusion injury in numerous tissues.
1019	19076445	The breadth of indications for PARP-1 injury make parthanatos a clinically important form of cell death to understand and control.
1020	19076445	Poly(ADP-ribose) polymerase-1 (PARP-1) is an abundant nuclear protein best known to facilitate DNA base excision repair.
1021	19076445	Recent work has expanded the physiologic functions of PARP-1, and it is clear that the full range of biologic actions of this important protein are not yet fully understood.
1022	19076445	Regulation of the product of PARP-1, poly(ADP-ribose) (PAR), is a dynamic process with PAR glycohydrolase playing the major role in the degradation of the polymer.
1023	19076445	Under pathophysiologic situations overactivation of PARP-1 results in unregulated PAR synthesis and widespread neuronal cell death.
1024	19076445	Once thought to be necrotic cell death resulting from energy failure, we have found that PARP-1-dependent cell death is dependent on the generation of PAR, which triggers the nuclear translocation of apoptosis-inducing factor resulting in caspase-independent cell death.
1025	19076445	PARP-1-dependent cell death has been implicated in tissues throughout the body and in diseases afflicting hundreds of millions worldwide, including stroke, Parkinson's disease, heart attack, diabetes, and ischemia reperfusion injury in numerous tissues.
1026	19076445	The breadth of indications for PARP-1 injury make parthanatos a clinically important form of cell death to understand and control.
1027	19076445	Poly(ADP-ribose) polymerase-1 (PARP-1) is an abundant nuclear protein best known to facilitate DNA base excision repair.
1028	19076445	Recent work has expanded the physiologic functions of PARP-1, and it is clear that the full range of biologic actions of this important protein are not yet fully understood.
1029	19076445	Regulation of the product of PARP-1, poly(ADP-ribose) (PAR), is a dynamic process with PAR glycohydrolase playing the major role in the degradation of the polymer.
1030	19076445	Under pathophysiologic situations overactivation of PARP-1 results in unregulated PAR synthesis and widespread neuronal cell death.
1031	19076445	Once thought to be necrotic cell death resulting from energy failure, we have found that PARP-1-dependent cell death is dependent on the generation of PAR, which triggers the nuclear translocation of apoptosis-inducing factor resulting in caspase-independent cell death.
1032	19076445	PARP-1-dependent cell death has been implicated in tissues throughout the body and in diseases afflicting hundreds of millions worldwide, including stroke, Parkinson's disease, heart attack, diabetes, and ischemia reperfusion injury in numerous tissues.
1033	19076445	The breadth of indications for PARP-1 injury make parthanatos a clinically important form of cell death to understand and control.
1034	19076445	Poly(ADP-ribose) polymerase-1 (PARP-1) is an abundant nuclear protein best known to facilitate DNA base excision repair.
1035	19076445	Recent work has expanded the physiologic functions of PARP-1, and it is clear that the full range of biologic actions of this important protein are not yet fully understood.
1036	19076445	Regulation of the product of PARP-1, poly(ADP-ribose) (PAR), is a dynamic process with PAR glycohydrolase playing the major role in the degradation of the polymer.
1037	19076445	Under pathophysiologic situations overactivation of PARP-1 results in unregulated PAR synthesis and widespread neuronal cell death.
1038	19076445	Once thought to be necrotic cell death resulting from energy failure, we have found that PARP-1-dependent cell death is dependent on the generation of PAR, which triggers the nuclear translocation of apoptosis-inducing factor resulting in caspase-independent cell death.
1039	19076445	PARP-1-dependent cell death has been implicated in tissues throughout the body and in diseases afflicting hundreds of millions worldwide, including stroke, Parkinson's disease, heart attack, diabetes, and ischemia reperfusion injury in numerous tissues.
1040	19076445	The breadth of indications for PARP-1 injury make parthanatos a clinically important form of cell death to understand and control.
1041	19076445	Poly(ADP-ribose) polymerase-1 (PARP-1) is an abundant nuclear protein best known to facilitate DNA base excision repair.
1042	19076445	Recent work has expanded the physiologic functions of PARP-1, and it is clear that the full range of biologic actions of this important protein are not yet fully understood.
1043	19076445	Regulation of the product of PARP-1, poly(ADP-ribose) (PAR), is a dynamic process with PAR glycohydrolase playing the major role in the degradation of the polymer.
1044	19076445	Under pathophysiologic situations overactivation of PARP-1 results in unregulated PAR synthesis and widespread neuronal cell death.
1045	19076445	Once thought to be necrotic cell death resulting from energy failure, we have found that PARP-1-dependent cell death is dependent on the generation of PAR, which triggers the nuclear translocation of apoptosis-inducing factor resulting in caspase-independent cell death.
1046	19076445	PARP-1-dependent cell death has been implicated in tissues throughout the body and in diseases afflicting hundreds of millions worldwide, including stroke, Parkinson's disease, heart attack, diabetes, and ischemia reperfusion injury in numerous tissues.
1047	19076445	The breadth of indications for PARP-1 injury make parthanatos a clinically important form of cell death to understand and control.
1048	19076445	Poly(ADP-ribose) polymerase-1 (PARP-1) is an abundant nuclear protein best known to facilitate DNA base excision repair.
1049	19076445	Recent work has expanded the physiologic functions of PARP-1, and it is clear that the full range of biologic actions of this important protein are not yet fully understood.
1050	19076445	Regulation of the product of PARP-1, poly(ADP-ribose) (PAR), is a dynamic process with PAR glycohydrolase playing the major role in the degradation of the polymer.
1051	19076445	Under pathophysiologic situations overactivation of PARP-1 results in unregulated PAR synthesis and widespread neuronal cell death.
1052	19076445	Once thought to be necrotic cell death resulting from energy failure, we have found that PARP-1-dependent cell death is dependent on the generation of PAR, which triggers the nuclear translocation of apoptosis-inducing factor resulting in caspase-independent cell death.
1053	19076445	PARP-1-dependent cell death has been implicated in tissues throughout the body and in diseases afflicting hundreds of millions worldwide, including stroke, Parkinson's disease, heart attack, diabetes, and ischemia reperfusion injury in numerous tissues.
1054	19076445	The breadth of indications for PARP-1 injury make parthanatos a clinically important form of cell death to understand and control.
1055	19076445	Poly(ADP-ribose) polymerase-1 (PARP-1) is an abundant nuclear protein best known to facilitate DNA base excision repair.
1056	19076445	Recent work has expanded the physiologic functions of PARP-1, and it is clear that the full range of biologic actions of this important protein are not yet fully understood.
1057	19076445	Regulation of the product of PARP-1, poly(ADP-ribose) (PAR), is a dynamic process with PAR glycohydrolase playing the major role in the degradation of the polymer.
1058	19076445	Under pathophysiologic situations overactivation of PARP-1 results in unregulated PAR synthesis and widespread neuronal cell death.
1059	19076445	Once thought to be necrotic cell death resulting from energy failure, we have found that PARP-1-dependent cell death is dependent on the generation of PAR, which triggers the nuclear translocation of apoptosis-inducing factor resulting in caspase-independent cell death.
1060	19076445	PARP-1-dependent cell death has been implicated in tissues throughout the body and in diseases afflicting hundreds of millions worldwide, including stroke, Parkinson's disease, heart attack, diabetes, and ischemia reperfusion injury in numerous tissues.
1061	19076445	The breadth of indications for PARP-1 injury make parthanatos a clinically important form of cell death to understand and control.
1062	19273119	Poly-ADP-ribose polymerase-1 (PARP-1)'s roles in the cell span from maintaining life to inducing death.
1063	19273119	The processes PARP-1 is involved in include DNA repair, DNA transcription, mitosis, and cell death.
1064	19273119	Genetic deletion of PARP-1 revealed that PARP-1 overactivation underlies cell death in models of stroke, diabetes, inflammation and neurodegeneration.
1065	19273119	Since interfering with PARP-1 mediated cell death will be clinically beneficial, great effort has been invested into understanding mechanisms downstream of PARP-1 overactivation.
1066	19273119	Recent evidence shows that poly-ADP ribose (PAR) polymer itself can act as a cell death effector downstream of PARP-1.
1067	19273119	In this review, we will present evidence and questions raised by these recent findings, and summarize the proposed mechanisms by which PARP-1 overactivation kills.
1068	19273119	It is evident that further understanding of parthanatos opens up new avenues for therapy in ameliorating diseases related to PARP-1 overactivation.
1069	19273119	Poly-ADP-ribose polymerase-1 (PARP-1)'s roles in the cell span from maintaining life to inducing death.
1070	19273119	The processes PARP-1 is involved in include DNA repair, DNA transcription, mitosis, and cell death.
1071	19273119	Genetic deletion of PARP-1 revealed that PARP-1 overactivation underlies cell death in models of stroke, diabetes, inflammation and neurodegeneration.
1072	19273119	Since interfering with PARP-1 mediated cell death will be clinically beneficial, great effort has been invested into understanding mechanisms downstream of PARP-1 overactivation.
1073	19273119	Recent evidence shows that poly-ADP ribose (PAR) polymer itself can act as a cell death effector downstream of PARP-1.
1074	19273119	In this review, we will present evidence and questions raised by these recent findings, and summarize the proposed mechanisms by which PARP-1 overactivation kills.
1075	19273119	It is evident that further understanding of parthanatos opens up new avenues for therapy in ameliorating diseases related to PARP-1 overactivation.
1076	19273119	Poly-ADP-ribose polymerase-1 (PARP-1)'s roles in the cell span from maintaining life to inducing death.
1077	19273119	The processes PARP-1 is involved in include DNA repair, DNA transcription, mitosis, and cell death.
1078	19273119	Genetic deletion of PARP-1 revealed that PARP-1 overactivation underlies cell death in models of stroke, diabetes, inflammation and neurodegeneration.
1079	19273119	Since interfering with PARP-1 mediated cell death will be clinically beneficial, great effort has been invested into understanding mechanisms downstream of PARP-1 overactivation.
1080	19273119	Recent evidence shows that poly-ADP ribose (PAR) polymer itself can act as a cell death effector downstream of PARP-1.
1081	19273119	In this review, we will present evidence and questions raised by these recent findings, and summarize the proposed mechanisms by which PARP-1 overactivation kills.
1082	19273119	It is evident that further understanding of parthanatos opens up new avenues for therapy in ameliorating diseases related to PARP-1 overactivation.
1083	19273119	Poly-ADP-ribose polymerase-1 (PARP-1)'s roles in the cell span from maintaining life to inducing death.
1084	19273119	The processes PARP-1 is involved in include DNA repair, DNA transcription, mitosis, and cell death.
1085	19273119	Genetic deletion of PARP-1 revealed that PARP-1 overactivation underlies cell death in models of stroke, diabetes, inflammation and neurodegeneration.
1086	19273119	Since interfering with PARP-1 mediated cell death will be clinically beneficial, great effort has been invested into understanding mechanisms downstream of PARP-1 overactivation.
1087	19273119	Recent evidence shows that poly-ADP ribose (PAR) polymer itself can act as a cell death effector downstream of PARP-1.
1088	19273119	In this review, we will present evidence and questions raised by these recent findings, and summarize the proposed mechanisms by which PARP-1 overactivation kills.
1089	19273119	It is evident that further understanding of parthanatos opens up new avenues for therapy in ameliorating diseases related to PARP-1 overactivation.
1090	19273119	Poly-ADP-ribose polymerase-1 (PARP-1)'s roles in the cell span from maintaining life to inducing death.
1091	19273119	The processes PARP-1 is involved in include DNA repair, DNA transcription, mitosis, and cell death.
1092	19273119	Genetic deletion of PARP-1 revealed that PARP-1 overactivation underlies cell death in models of stroke, diabetes, inflammation and neurodegeneration.
1093	19273119	Since interfering with PARP-1 mediated cell death will be clinically beneficial, great effort has been invested into understanding mechanisms downstream of PARP-1 overactivation.
1094	19273119	Recent evidence shows that poly-ADP ribose (PAR) polymer itself can act as a cell death effector downstream of PARP-1.
1095	19273119	In this review, we will present evidence and questions raised by these recent findings, and summarize the proposed mechanisms by which PARP-1 overactivation kills.
1096	19273119	It is evident that further understanding of parthanatos opens up new avenues for therapy in ameliorating diseases related to PARP-1 overactivation.
1097	19273119	Poly-ADP-ribose polymerase-1 (PARP-1)'s roles in the cell span from maintaining life to inducing death.
1098	19273119	The processes PARP-1 is involved in include DNA repair, DNA transcription, mitosis, and cell death.
1099	19273119	Genetic deletion of PARP-1 revealed that PARP-1 overactivation underlies cell death in models of stroke, diabetes, inflammation and neurodegeneration.
1100	19273119	Since interfering with PARP-1 mediated cell death will be clinically beneficial, great effort has been invested into understanding mechanisms downstream of PARP-1 overactivation.
1101	19273119	Recent evidence shows that poly-ADP ribose (PAR) polymer itself can act as a cell death effector downstream of PARP-1.
1102	19273119	In this review, we will present evidence and questions raised by these recent findings, and summarize the proposed mechanisms by which PARP-1 overactivation kills.
1103	19273119	It is evident that further understanding of parthanatos opens up new avenues for therapy in ameliorating diseases related to PARP-1 overactivation.
1104	19273119	Poly-ADP-ribose polymerase-1 (PARP-1)'s roles in the cell span from maintaining life to inducing death.
1105	19273119	The processes PARP-1 is involved in include DNA repair, DNA transcription, mitosis, and cell death.
1106	19273119	Genetic deletion of PARP-1 revealed that PARP-1 overactivation underlies cell death in models of stroke, diabetes, inflammation and neurodegeneration.
1107	19273119	Since interfering with PARP-1 mediated cell death will be clinically beneficial, great effort has been invested into understanding mechanisms downstream of PARP-1 overactivation.
1108	19273119	Recent evidence shows that poly-ADP ribose (PAR) polymer itself can act as a cell death effector downstream of PARP-1.
1109	19273119	In this review, we will present evidence and questions raised by these recent findings, and summarize the proposed mechanisms by which PARP-1 overactivation kills.
1110	19273119	It is evident that further understanding of parthanatos opens up new avenues for therapy in ameliorating diseases related to PARP-1 overactivation.
1111	19321592	Recently, we identified several flavonoids as inhibitors of the nuclear enzyme poly(ADP-ribose) polymerase (PARP)-1 in vitro and in vivo.
1112	19321592	PARP-1 is recognized as coactivator of nuclear factor-kappaB and plays a role in the pathophysiology of diseases with low-grade systemic inflammation, such as chronic obstructive pulmonary disease (COPD) and type 2 diabetes (T2D).
1113	19321592	In this study, we assessed the antiinflammatory effects of flavonoids with varying PARP-1-inhibiting effects in whole blood from male patients with COPD or T2D and healthy men.
1114	19321592	Concentrations of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, -8, and -10 were measured in the supernatant.
1115	19321592	Preincubation with fisetin and tricetin strongly attenuated LPS-induced increases in concentrations of TNFalpha in blood from COPD patients [mean (+/- SEM): -41 +/- 4% (fisetin) and -31 +/- 4% (tricetin); P < 0.001] and IL-6 in blood from T2D patients [-31 +/- 5% (fisetin) and -29 +/- 6% (tricetin); P < or = 0.001].
1116	19321592	Moreover, LPS-induced changes in TNFalpha and IL-6 concentrations were positively correlated with the extent of reduction by fisetin and tricetin.
1117	19321592	The PARP-1-inhibiting flavonoids fisetin and tricetin were able to attenuate LPS-induced cytokine release from leukocytes of patients with chronic systemic inflammation, indicating a potential application as nutraceutical agents for these patient groups.
1118	19321592	Recently, we identified several flavonoids as inhibitors of the nuclear enzyme poly(ADP-ribose) polymerase (PARP)-1 in vitro and in vivo.
1119	19321592	PARP-1 is recognized as coactivator of nuclear factor-kappaB and plays a role in the pathophysiology of diseases with low-grade systemic inflammation, such as chronic obstructive pulmonary disease (COPD) and type 2 diabetes (T2D).
1120	19321592	In this study, we assessed the antiinflammatory effects of flavonoids with varying PARP-1-inhibiting effects in whole blood from male patients with COPD or T2D and healthy men.
1121	19321592	Concentrations of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, -8, and -10 were measured in the supernatant.
1122	19321592	Preincubation with fisetin and tricetin strongly attenuated LPS-induced increases in concentrations of TNFalpha in blood from COPD patients [mean (+/- SEM): -41 +/- 4% (fisetin) and -31 +/- 4% (tricetin); P < 0.001] and IL-6 in blood from T2D patients [-31 +/- 5% (fisetin) and -29 +/- 6% (tricetin); P < or = 0.001].
1123	19321592	Moreover, LPS-induced changes in TNFalpha and IL-6 concentrations were positively correlated with the extent of reduction by fisetin and tricetin.
1124	19321592	The PARP-1-inhibiting flavonoids fisetin and tricetin were able to attenuate LPS-induced cytokine release from leukocytes of patients with chronic systemic inflammation, indicating a potential application as nutraceutical agents for these patient groups.
1125	19321592	Recently, we identified several flavonoids as inhibitors of the nuclear enzyme poly(ADP-ribose) polymerase (PARP)-1 in vitro and in vivo.
1126	19321592	PARP-1 is recognized as coactivator of nuclear factor-kappaB and plays a role in the pathophysiology of diseases with low-grade systemic inflammation, such as chronic obstructive pulmonary disease (COPD) and type 2 diabetes (T2D).
1127	19321592	In this study, we assessed the antiinflammatory effects of flavonoids with varying PARP-1-inhibiting effects in whole blood from male patients with COPD or T2D and healthy men.
1128	19321592	Concentrations of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, -8, and -10 were measured in the supernatant.
1129	19321592	Preincubation with fisetin and tricetin strongly attenuated LPS-induced increases in concentrations of TNFalpha in blood from COPD patients [mean (+/- SEM): -41 +/- 4% (fisetin) and -31 +/- 4% (tricetin); P < 0.001] and IL-6 in blood from T2D patients [-31 +/- 5% (fisetin) and -29 +/- 6% (tricetin); P < or = 0.001].
1130	19321592	Moreover, LPS-induced changes in TNFalpha and IL-6 concentrations were positively correlated with the extent of reduction by fisetin and tricetin.
1131	19321592	The PARP-1-inhibiting flavonoids fisetin and tricetin were able to attenuate LPS-induced cytokine release from leukocytes of patients with chronic systemic inflammation, indicating a potential application as nutraceutical agents for these patient groups.
1132	19321592	Recently, we identified several flavonoids as inhibitors of the nuclear enzyme poly(ADP-ribose) polymerase (PARP)-1 in vitro and in vivo.
1133	19321592	PARP-1 is recognized as coactivator of nuclear factor-kappaB and plays a role in the pathophysiology of diseases with low-grade systemic inflammation, such as chronic obstructive pulmonary disease (COPD) and type 2 diabetes (T2D).
1134	19321592	In this study, we assessed the antiinflammatory effects of flavonoids with varying PARP-1-inhibiting effects in whole blood from male patients with COPD or T2D and healthy men.
1135	19321592	Concentrations of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, -8, and -10 were measured in the supernatant.
1136	19321592	Preincubation with fisetin and tricetin strongly attenuated LPS-induced increases in concentrations of TNFalpha in blood from COPD patients [mean (+/- SEM): -41 +/- 4% (fisetin) and -31 +/- 4% (tricetin); P < 0.001] and IL-6 in blood from T2D patients [-31 +/- 5% (fisetin) and -29 +/- 6% (tricetin); P < or = 0.001].
1137	19321592	Moreover, LPS-induced changes in TNFalpha and IL-6 concentrations were positively correlated with the extent of reduction by fisetin and tricetin.
1138	19321592	The PARP-1-inhibiting flavonoids fisetin and tricetin were able to attenuate LPS-induced cytokine release from leukocytes of patients with chronic systemic inflammation, indicating a potential application as nutraceutical agents for these patient groups.
1139	19362586	PARP-1, the best characterized member of the PARP family, which currently comprises 18 members, is an abundant nuclear enzyme implicated in cellular responses to DNA injury provoked by genotoxic stress.
1140	19362586	PARP-1 is essential to the repair of DNA single-strand breaks via the base excision repair pathway.
1141	19362586	Inhibitors of PARP-1 have been shown to enhance the cytotoxic effects of ionizing radiation and DNA-damaging chemotherapy agents, such as the methylating agents and topoisomerase I inhibitors.
1142	19362586	Recent in vitro and in vivo evidence suggests that PARP inhibitors could be used not only as chemo/radiotherapy sensitizers, but also as single agents to selectively kill cancers defective in DNA repair, specifically cancers with mutations in the breast cancer-associated genes (BRCA1 and BRCA2).
1143	19362586	PARP-1, the best characterized member of the PARP family, which currently comprises 18 members, is an abundant nuclear enzyme implicated in cellular responses to DNA injury provoked by genotoxic stress.
1144	19362586	PARP-1 is essential to the repair of DNA single-strand breaks via the base excision repair pathway.
1145	19362586	Inhibitors of PARP-1 have been shown to enhance the cytotoxic effects of ionizing radiation and DNA-damaging chemotherapy agents, such as the methylating agents and topoisomerase I inhibitors.
1146	19362586	Recent in vitro and in vivo evidence suggests that PARP inhibitors could be used not only as chemo/radiotherapy sensitizers, but also as single agents to selectively kill cancers defective in DNA repair, specifically cancers with mutations in the breast cancer-associated genes (BRCA1 and BRCA2).
1147	19362586	PARP-1, the best characterized member of the PARP family, which currently comprises 18 members, is an abundant nuclear enzyme implicated in cellular responses to DNA injury provoked by genotoxic stress.
1148	19362586	PARP-1 is essential to the repair of DNA single-strand breaks via the base excision repair pathway.
1149	19362586	Inhibitors of PARP-1 have been shown to enhance the cytotoxic effects of ionizing radiation and DNA-damaging chemotherapy agents, such as the methylating agents and topoisomerase I inhibitors.
1150	19362586	Recent in vitro and in vivo evidence suggests that PARP inhibitors could be used not only as chemo/radiotherapy sensitizers, but also as single agents to selectively kill cancers defective in DNA repair, specifically cancers with mutations in the breast cancer-associated genes (BRCA1 and BRCA2).
1151	20422335	The absence of cardiomyopathy is accompanied by increased activities of CAT, MnSOD and GST in long-term diabetes in rats.
1152	20422335	The activities of the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT) and glutathione S-transferase (GST), the incidence of DNA damage, the activation of poly (ADP-ribose) polymerase-1 (PARP-1), a marker of DNA repair, and connective tissue growth factor (CTGF), a marker of tissue fibrosis, were examined in the hearts of rats for 16 weeks after diabetes induction by streptozotocin (STZ) administration.
1153	20422335	While total SOD and CuZn-SOD exhibited progressively decreasing activities, those of Mn-SOD and GST were elevated.
1154	20422335	Neither DNA strand breaks (apoptosis or necrosis) nor changes in PARP-1 activity and in CTGF levels (fibrosis) were observed in the diabetic heart.
1155	20422335	The absence of cardiomyopathy is accompanied with increased activities of CAT, MnSOD and GST.
1156	20422335	The absence of cardiomyopathy is accompanied by increased activities of CAT, MnSOD and GST in long-term diabetes in rats.
1157	20422335	The activities of the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT) and glutathione S-transferase (GST), the incidence of DNA damage, the activation of poly (ADP-ribose) polymerase-1 (PARP-1), a marker of DNA repair, and connective tissue growth factor (CTGF), a marker of tissue fibrosis, were examined in the hearts of rats for 16 weeks after diabetes induction by streptozotocin (STZ) administration.
1158	20422335	While total SOD and CuZn-SOD exhibited progressively decreasing activities, those of Mn-SOD and GST were elevated.
1159	20422335	Neither DNA strand breaks (apoptosis or necrosis) nor changes in PARP-1 activity and in CTGF levels (fibrosis) were observed in the diabetic heart.
1160	20422335	The absence of cardiomyopathy is accompanied with increased activities of CAT, MnSOD and GST.
1161	20561897	Inflammatory and age-related pathologies in mice with ectopic expression of human PARP-1.
1162	20561897	Poly(ADP-ribose) polymerase-1 (PARP-1) is a sensor for DNA strand breaks and some unusual DNA structures and catalyzes poly(ADP-ribosyl)ation of nuclear proteins with NAD(+) serving as substrate.
1163	20561897	PARP-1 is involved in the regulation of genomic integrity, transcription, inflammation, and cell death.
1164	20561897	Due to its versatile role, PARP-1 is discussed both as a longevity factor and as an aging-promoting factor.
1165	20561897	A caveat in mouse genetic engineering: ectopic gene targeting in ES cells by bidirectional extension of the homology arms of a gene replacement vector carrying human PARP-1.
1166	20561897	Inflammatory and age-related pathologies in mice with ectopic expression of human PARP-1.
1167	20561897	Poly(ADP-ribose) polymerase-1 (PARP-1) is a sensor for DNA strand breaks and some unusual DNA structures and catalyzes poly(ADP-ribosyl)ation of nuclear proteins with NAD(+) serving as substrate.
1168	20561897	PARP-1 is involved in the regulation of genomic integrity, transcription, inflammation, and cell death.
1169	20561897	Due to its versatile role, PARP-1 is discussed both as a longevity factor and as an aging-promoting factor.
1170	20561897	A caveat in mouse genetic engineering: ectopic gene targeting in ES cells by bidirectional extension of the homology arms of a gene replacement vector carrying human PARP-1.
1171	20561897	Inflammatory and age-related pathologies in mice with ectopic expression of human PARP-1.
1172	20561897	Poly(ADP-ribose) polymerase-1 (PARP-1) is a sensor for DNA strand breaks and some unusual DNA structures and catalyzes poly(ADP-ribosyl)ation of nuclear proteins with NAD(+) serving as substrate.
1173	20561897	PARP-1 is involved in the regulation of genomic integrity, transcription, inflammation, and cell death.
1174	20561897	Due to its versatile role, PARP-1 is discussed both as a longevity factor and as an aging-promoting factor.
1175	20561897	A caveat in mouse genetic engineering: ectopic gene targeting in ES cells by bidirectional extension of the homology arms of a gene replacement vector carrying human PARP-1.
1176	20561897	Inflammatory and age-related pathologies in mice with ectopic expression of human PARP-1.
1177	20561897	Poly(ADP-ribose) polymerase-1 (PARP-1) is a sensor for DNA strand breaks and some unusual DNA structures and catalyzes poly(ADP-ribosyl)ation of nuclear proteins with NAD(+) serving as substrate.
1178	20561897	PARP-1 is involved in the regulation of genomic integrity, transcription, inflammation, and cell death.
1179	20561897	Due to its versatile role, PARP-1 is discussed both as a longevity factor and as an aging-promoting factor.
1180	20561897	A caveat in mouse genetic engineering: ectopic gene targeting in ES cells by bidirectional extension of the homology arms of a gene replacement vector carrying human PARP-1.
1181	20561897	Inflammatory and age-related pathologies in mice with ectopic expression of human PARP-1.
1182	20561897	Poly(ADP-ribose) polymerase-1 (PARP-1) is a sensor for DNA strand breaks and some unusual DNA structures and catalyzes poly(ADP-ribosyl)ation of nuclear proteins with NAD(+) serving as substrate.
1183	20561897	PARP-1 is involved in the regulation of genomic integrity, transcription, inflammation, and cell death.
1184	20561897	Due to its versatile role, PARP-1 is discussed both as a longevity factor and as an aging-promoting factor.
1185	20561897	A caveat in mouse genetic engineering: ectopic gene targeting in ES cells by bidirectional extension of the homology arms of a gene replacement vector carrying human PARP-1.
1186	20619687	iNOS induction and PARP-1 activation in human atherosclerotic lesions: an immunohistochemical and ultrastructural approach.
1187	20621183	Poly(ADP-ribose) polymerase-1 (PARP-1) gene deficiency alleviates diabetic kidney disease.
1188	20621183	This study evaluated the role for PARP-1 in diabetic kidney disease using the PARP-1-deficient mouse.
1189	20621183	PARP-1 protein expression (Western blot analysis) in the renal cortex was similar in non-diabetic and diabetic wild-type mice (100% and 107%) whereas all knockouts were PARP-1-negative.
1190	20621183	PARP-1 gene deficiency reduced urinary albumin (ELISA) and protein excretion prevented diabetes-induced kidney hypertrophy, and decreased mesangial expansion and collagen deposition (both assessed by histochemistry) as well as fibronectin expression.
1191	20621183	Renal podocyte loss (immunohistochemistry) and nitrotyrosine and transforming growth factor-β₁ accumulations (both by ELISA) were slightly lower in diabetic PARP-1-/- mice, but the differences with diabetic wild-type group did not achieve statistical significance.
1192	20621183	In conclusion, PARP-1-/- gene deficiency alleviates although does not completely prevent diabetic kidney disease.
1193	20621183	Poly(ADP-ribose) polymerase-1 (PARP-1) gene deficiency alleviates diabetic kidney disease.
1194	20621183	This study evaluated the role for PARP-1 in diabetic kidney disease using the PARP-1-deficient mouse.
1195	20621183	PARP-1 protein expression (Western blot analysis) in the renal cortex was similar in non-diabetic and diabetic wild-type mice (100% and 107%) whereas all knockouts were PARP-1-negative.
1196	20621183	PARP-1 gene deficiency reduced urinary albumin (ELISA) and protein excretion prevented diabetes-induced kidney hypertrophy, and decreased mesangial expansion and collagen deposition (both assessed by histochemistry) as well as fibronectin expression.
1197	20621183	Renal podocyte loss (immunohistochemistry) and nitrotyrosine and transforming growth factor-β₁ accumulations (both by ELISA) were slightly lower in diabetic PARP-1-/- mice, but the differences with diabetic wild-type group did not achieve statistical significance.
1198	20621183	In conclusion, PARP-1-/- gene deficiency alleviates although does not completely prevent diabetic kidney disease.
1199	20621183	Poly(ADP-ribose) polymerase-1 (PARP-1) gene deficiency alleviates diabetic kidney disease.
1200	20621183	This study evaluated the role for PARP-1 in diabetic kidney disease using the PARP-1-deficient mouse.
1201	20621183	PARP-1 protein expression (Western blot analysis) in the renal cortex was similar in non-diabetic and diabetic wild-type mice (100% and 107%) whereas all knockouts were PARP-1-negative.
1202	20621183	PARP-1 gene deficiency reduced urinary albumin (ELISA) and protein excretion prevented diabetes-induced kidney hypertrophy, and decreased mesangial expansion and collagen deposition (both assessed by histochemistry) as well as fibronectin expression.
1203	20621183	Renal podocyte loss (immunohistochemistry) and nitrotyrosine and transforming growth factor-β₁ accumulations (both by ELISA) were slightly lower in diabetic PARP-1-/- mice, but the differences with diabetic wild-type group did not achieve statistical significance.
1204	20621183	In conclusion, PARP-1-/- gene deficiency alleviates although does not completely prevent diabetic kidney disease.
1205	20621183	Poly(ADP-ribose) polymerase-1 (PARP-1) gene deficiency alleviates diabetic kidney disease.
1206	20621183	This study evaluated the role for PARP-1 in diabetic kidney disease using the PARP-1-deficient mouse.
1207	20621183	PARP-1 protein expression (Western blot analysis) in the renal cortex was similar in non-diabetic and diabetic wild-type mice (100% and 107%) whereas all knockouts were PARP-1-negative.
1208	20621183	PARP-1 gene deficiency reduced urinary albumin (ELISA) and protein excretion prevented diabetes-induced kidney hypertrophy, and decreased mesangial expansion and collagen deposition (both assessed by histochemistry) as well as fibronectin expression.
1209	20621183	Renal podocyte loss (immunohistochemistry) and nitrotyrosine and transforming growth factor-β₁ accumulations (both by ELISA) were slightly lower in diabetic PARP-1-/- mice, but the differences with diabetic wild-type group did not achieve statistical significance.
1210	20621183	In conclusion, PARP-1-/- gene deficiency alleviates although does not completely prevent diabetic kidney disease.
1211	20621183	Poly(ADP-ribose) polymerase-1 (PARP-1) gene deficiency alleviates diabetic kidney disease.
1212	20621183	This study evaluated the role for PARP-1 in diabetic kidney disease using the PARP-1-deficient mouse.
1213	20621183	PARP-1 protein expression (Western blot analysis) in the renal cortex was similar in non-diabetic and diabetic wild-type mice (100% and 107%) whereas all knockouts were PARP-1-negative.
1214	20621183	PARP-1 gene deficiency reduced urinary albumin (ELISA) and protein excretion prevented diabetes-induced kidney hypertrophy, and decreased mesangial expansion and collagen deposition (both assessed by histochemistry) as well as fibronectin expression.
1215	20621183	Renal podocyte loss (immunohistochemistry) and nitrotyrosine and transforming growth factor-β₁ accumulations (both by ELISA) were slightly lower in diabetic PARP-1-/- mice, but the differences with diabetic wild-type group did not achieve statistical significance.
1216	20621183	In conclusion, PARP-1-/- gene deficiency alleviates although does not completely prevent diabetic kidney disease.
1217	20621183	Poly(ADP-ribose) polymerase-1 (PARP-1) gene deficiency alleviates diabetic kidney disease.
1218	20621183	This study evaluated the role for PARP-1 in diabetic kidney disease using the PARP-1-deficient mouse.
1219	20621183	PARP-1 protein expression (Western blot analysis) in the renal cortex was similar in non-diabetic and diabetic wild-type mice (100% and 107%) whereas all knockouts were PARP-1-negative.
1220	20621183	PARP-1 gene deficiency reduced urinary albumin (ELISA) and protein excretion prevented diabetes-induced kidney hypertrophy, and decreased mesangial expansion and collagen deposition (both assessed by histochemistry) as well as fibronectin expression.
1221	20621183	Renal podocyte loss (immunohistochemistry) and nitrotyrosine and transforming growth factor-β₁ accumulations (both by ELISA) were slightly lower in diabetic PARP-1-/- mice, but the differences with diabetic wild-type group did not achieve statistical significance.
1222	20621183	In conclusion, PARP-1-/- gene deficiency alleviates although does not completely prevent diabetic kidney disease.
1223	20633699	Poly(ADP-ribose) polymerase-1 (PARP-1) and its therapeutic implications.
1224	20633699	While an 18 member superfamily of PARPs has been identified, however PARP-1 the most abundant isoform accounts for more than 90% of its functions.
1225	20633699	PARP-1 works as DNA damage nick sensor, which uses NAD(+) to form polymers of ADP-ribose (PAR) and nicotinamide.
1226	20633699	Three consequences of the activation of PARP-1 are particularly important for drug development: first, its role in DNA repair; second, its capacity to deplete cellular energetic pools, which culminates in cell dysfunction and necrosis; and third, its capacity to promote the transcription of proinflammatory genes.
1227	20633699	Through this article we have tried to develop a brief and simplified picture of the principal physiological and pathophysiological roles governed by PARP-1 and its therapeutic implications.
1228	20633699	Poly(ADP-ribose) polymerase-1 (PARP-1) and its therapeutic implications.
1229	20633699	While an 18 member superfamily of PARPs has been identified, however PARP-1 the most abundant isoform accounts for more than 90% of its functions.
1230	20633699	PARP-1 works as DNA damage nick sensor, which uses NAD(+) to form polymers of ADP-ribose (PAR) and nicotinamide.
1231	20633699	Three consequences of the activation of PARP-1 are particularly important for drug development: first, its role in DNA repair; second, its capacity to deplete cellular energetic pools, which culminates in cell dysfunction and necrosis; and third, its capacity to promote the transcription of proinflammatory genes.
1232	20633699	Through this article we have tried to develop a brief and simplified picture of the principal physiological and pathophysiological roles governed by PARP-1 and its therapeutic implications.
1233	20633699	Poly(ADP-ribose) polymerase-1 (PARP-1) and its therapeutic implications.
1234	20633699	While an 18 member superfamily of PARPs has been identified, however PARP-1 the most abundant isoform accounts for more than 90% of its functions.
1235	20633699	PARP-1 works as DNA damage nick sensor, which uses NAD(+) to form polymers of ADP-ribose (PAR) and nicotinamide.
1236	20633699	Three consequences of the activation of PARP-1 are particularly important for drug development: first, its role in DNA repair; second, its capacity to deplete cellular energetic pools, which culminates in cell dysfunction and necrosis; and third, its capacity to promote the transcription of proinflammatory genes.
1237	20633699	Through this article we have tried to develop a brief and simplified picture of the principal physiological and pathophysiological roles governed by PARP-1 and its therapeutic implications.
1238	20633699	Poly(ADP-ribose) polymerase-1 (PARP-1) and its therapeutic implications.
1239	20633699	While an 18 member superfamily of PARPs has been identified, however PARP-1 the most abundant isoform accounts for more than 90% of its functions.
1240	20633699	PARP-1 works as DNA damage nick sensor, which uses NAD(+) to form polymers of ADP-ribose (PAR) and nicotinamide.
1241	20633699	Three consequences of the activation of PARP-1 are particularly important for drug development: first, its role in DNA repair; second, its capacity to deplete cellular energetic pools, which culminates in cell dysfunction and necrosis; and third, its capacity to promote the transcription of proinflammatory genes.
1242	20633699	Through this article we have tried to develop a brief and simplified picture of the principal physiological and pathophysiological roles governed by PARP-1 and its therapeutic implications.
1243	20633699	Poly(ADP-ribose) polymerase-1 (PARP-1) and its therapeutic implications.
1244	20633699	While an 18 member superfamily of PARPs has been identified, however PARP-1 the most abundant isoform accounts for more than 90% of its functions.
1245	20633699	PARP-1 works as DNA damage nick sensor, which uses NAD(+) to form polymers of ADP-ribose (PAR) and nicotinamide.
1246	20633699	Three consequences of the activation of PARP-1 are particularly important for drug development: first, its role in DNA repair; second, its capacity to deplete cellular energetic pools, which culminates in cell dysfunction and necrosis; and third, its capacity to promote the transcription of proinflammatory genes.
1247	20633699	Through this article we have tried to develop a brief and simplified picture of the principal physiological and pathophysiological roles governed by PARP-1 and its therapeutic implications.
1248	20870608	In a cell, the activation of PARP-1 caused by excitotoxicity leads to Parthanatos, which is also known as PARP-1-dependent cell death.
1249	21458523	Glucagon-like peptide 1 protects microvascular endothelial cells by inactivating the PARP-1/iNOS/NO pathway.
1250	21458523	However, to date, the anti-apoptosis mechanism by which GLP-1 acts on MILE SVEN 1 (MS-1) cells has not been fully explored with regard to the intracellular signaling pathway.
1251	21458523	We wondered whether GLP-1 exerts its anti-apoptosis effects by inactivating the PARP-1/iNOS/NO pathway in oxidized low-density-lipoprotein (oxLDL)-induced apoptosis in mouse IMECs (MS-1 cells), which may linked to GLP-1R/cAMP levels.
1252	21458523	MTT assay revealed that 2-h pre-incubation with GLP-1 markedly restored the oxLDL-induced loss of MS-1 viability in a concentration-dependent manner.
1253	21458523	Pre-incubating MS-1 cells with GLP-1 reduced cell apoptosis.
1254	21458523	Finally, GLP-1 could efficiently prevent the upregulation of poly(ADP-ribose) polymerase-1/nitrotyrosine and inducible NO synthase protein.
1255	21458523	Our findings suggest that GLP-1 can effectively protect MS-1 cells against oxLDL-induced apoptosis, which may be important in preventing the pathogenesis of diabetes mellitus.
1256	21458523	Glucagon-like peptide 1 protects microvascular endothelial cells by inactivating the PARP-1/iNOS/NO pathway.
1257	21458523	However, to date, the anti-apoptosis mechanism by which GLP-1 acts on MILE SVEN 1 (MS-1) cells has not been fully explored with regard to the intracellular signaling pathway.
1258	21458523	We wondered whether GLP-1 exerts its anti-apoptosis effects by inactivating the PARP-1/iNOS/NO pathway in oxidized low-density-lipoprotein (oxLDL)-induced apoptosis in mouse IMECs (MS-1 cells), which may linked to GLP-1R/cAMP levels.
1259	21458523	MTT assay revealed that 2-h pre-incubation with GLP-1 markedly restored the oxLDL-induced loss of MS-1 viability in a concentration-dependent manner.
1260	21458523	Pre-incubating MS-1 cells with GLP-1 reduced cell apoptosis.
1261	21458523	Finally, GLP-1 could efficiently prevent the upregulation of poly(ADP-ribose) polymerase-1/nitrotyrosine and inducible NO synthase protein.
1262	21458523	Our findings suggest that GLP-1 can effectively protect MS-1 cells against oxLDL-induced apoptosis, which may be important in preventing the pathogenesis of diabetes mellitus.
1263	21697640	Adenosine thiamine triphosphate (AThTP) inhibits poly(ADP-ribose) polymerase-1 (PARP-1) activity.
1264	21697640	Overactivation of poly(ADP-ribose) polymerase-1 (PARP-1) has been demonstrated to result in various stress-related diseases, including diabetes mellitus.
1265	21697640	Deficiency of cellular nicotinamide adenine dinucleotide (NAD(+)) content, consumed by PARP-1 to add ADP-ribose moieties onto target proteins, contributes to pathophysiological conditions.
1266	21697640	These findings have led us to hypothesize that AThTP may modulate the activity of PARP-1.
1267	21697640	We have chemically synthesized AThTP and evaluated the effect of AThTP on recombinant PARP-1 enzyme activity.
1268	21697640	AThTP inhibited the PARP-1 activity at 10 µM, and a structural model of the PARP-1-AThTP complex highlighted the AThTP binding site.
1269	21697640	The results provide new insights into the pharmacological importance of AThTP as an inhibitor of PARP-1.
1270	21697640	Adenosine thiamine triphosphate (AThTP) inhibits poly(ADP-ribose) polymerase-1 (PARP-1) activity.
1271	21697640	Overactivation of poly(ADP-ribose) polymerase-1 (PARP-1) has been demonstrated to result in various stress-related diseases, including diabetes mellitus.
1272	21697640	Deficiency of cellular nicotinamide adenine dinucleotide (NAD(+)) content, consumed by PARP-1 to add ADP-ribose moieties onto target proteins, contributes to pathophysiological conditions.
1273	21697640	These findings have led us to hypothesize that AThTP may modulate the activity of PARP-1.
1274	21697640	We have chemically synthesized AThTP and evaluated the effect of AThTP on recombinant PARP-1 enzyme activity.
1275	21697640	AThTP inhibited the PARP-1 activity at 10 µM, and a structural model of the PARP-1-AThTP complex highlighted the AThTP binding site.
1276	21697640	The results provide new insights into the pharmacological importance of AThTP as an inhibitor of PARP-1.
1277	21697640	Adenosine thiamine triphosphate (AThTP) inhibits poly(ADP-ribose) polymerase-1 (PARP-1) activity.
1278	21697640	Overactivation of poly(ADP-ribose) polymerase-1 (PARP-1) has been demonstrated to result in various stress-related diseases, including diabetes mellitus.
1279	21697640	Deficiency of cellular nicotinamide adenine dinucleotide (NAD(+)) content, consumed by PARP-1 to add ADP-ribose moieties onto target proteins, contributes to pathophysiological conditions.
1280	21697640	These findings have led us to hypothesize that AThTP may modulate the activity of PARP-1.
1281	21697640	We have chemically synthesized AThTP and evaluated the effect of AThTP on recombinant PARP-1 enzyme activity.
1282	21697640	AThTP inhibited the PARP-1 activity at 10 µM, and a structural model of the PARP-1-AThTP complex highlighted the AThTP binding site.
1283	21697640	The results provide new insights into the pharmacological importance of AThTP as an inhibitor of PARP-1.
1284	21697640	Adenosine thiamine triphosphate (AThTP) inhibits poly(ADP-ribose) polymerase-1 (PARP-1) activity.
1285	21697640	Overactivation of poly(ADP-ribose) polymerase-1 (PARP-1) has been demonstrated to result in various stress-related diseases, including diabetes mellitus.
1286	21697640	Deficiency of cellular nicotinamide adenine dinucleotide (NAD(+)) content, consumed by PARP-1 to add ADP-ribose moieties onto target proteins, contributes to pathophysiological conditions.
1287	21697640	These findings have led us to hypothesize that AThTP may modulate the activity of PARP-1.
1288	21697640	We have chemically synthesized AThTP and evaluated the effect of AThTP on recombinant PARP-1 enzyme activity.
1289	21697640	AThTP inhibited the PARP-1 activity at 10 µM, and a structural model of the PARP-1-AThTP complex highlighted the AThTP binding site.
1290	21697640	The results provide new insights into the pharmacological importance of AThTP as an inhibitor of PARP-1.
1291	21697640	Adenosine thiamine triphosphate (AThTP) inhibits poly(ADP-ribose) polymerase-1 (PARP-1) activity.
1292	21697640	Overactivation of poly(ADP-ribose) polymerase-1 (PARP-1) has been demonstrated to result in various stress-related diseases, including diabetes mellitus.
1293	21697640	Deficiency of cellular nicotinamide adenine dinucleotide (NAD(+)) content, consumed by PARP-1 to add ADP-ribose moieties onto target proteins, contributes to pathophysiological conditions.
1294	21697640	These findings have led us to hypothesize that AThTP may modulate the activity of PARP-1.
1295	21697640	We have chemically synthesized AThTP and evaluated the effect of AThTP on recombinant PARP-1 enzyme activity.
1296	21697640	AThTP inhibited the PARP-1 activity at 10 µM, and a structural model of the PARP-1-AThTP complex highlighted the AThTP binding site.
1297	21697640	The results provide new insights into the pharmacological importance of AThTP as an inhibitor of PARP-1.
1298	21697640	Adenosine thiamine triphosphate (AThTP) inhibits poly(ADP-ribose) polymerase-1 (PARP-1) activity.
1299	21697640	Overactivation of poly(ADP-ribose) polymerase-1 (PARP-1) has been demonstrated to result in various stress-related diseases, including diabetes mellitus.
1300	21697640	Deficiency of cellular nicotinamide adenine dinucleotide (NAD(+)) content, consumed by PARP-1 to add ADP-ribose moieties onto target proteins, contributes to pathophysiological conditions.
1301	21697640	These findings have led us to hypothesize that AThTP may modulate the activity of PARP-1.
1302	21697640	We have chemically synthesized AThTP and evaluated the effect of AThTP on recombinant PARP-1 enzyme activity.
1303	21697640	AThTP inhibited the PARP-1 activity at 10 µM, and a structural model of the PARP-1-AThTP complex highlighted the AThTP binding site.
1304	21697640	The results provide new insights into the pharmacological importance of AThTP as an inhibitor of PARP-1.
1305	21697640	Adenosine thiamine triphosphate (AThTP) inhibits poly(ADP-ribose) polymerase-1 (PARP-1) activity.
1306	21697640	Overactivation of poly(ADP-ribose) polymerase-1 (PARP-1) has been demonstrated to result in various stress-related diseases, including diabetes mellitus.
1307	21697640	Deficiency of cellular nicotinamide adenine dinucleotide (NAD(+)) content, consumed by PARP-1 to add ADP-ribose moieties onto target proteins, contributes to pathophysiological conditions.
1308	21697640	These findings have led us to hypothesize that AThTP may modulate the activity of PARP-1.
1309	21697640	We have chemically synthesized AThTP and evaluated the effect of AThTP on recombinant PARP-1 enzyme activity.
1310	21697640	AThTP inhibited the PARP-1 activity at 10 µM, and a structural model of the PARP-1-AThTP complex highlighted the AThTP binding site.
1311	21697640	The results provide new insights into the pharmacological importance of AThTP as an inhibitor of PARP-1.
1312	22454481	We hypothesized that increased poly(ADP-ribose) polymerase 1 (PARP-1) activity contributes to microvascular dysfunction in T2DM.
1313	22454481	T2DM (db(-)/db(-)) and nondiabetic control (db(-)/db(+)) mice were treated with 2 different PARP-1 inhibitors (INO-1001, 5 mg/kg per day and ABT-888, 15 mg/kg per day) for 2 weeks.
1314	22454481	These results were associated with decreased endothelial NO synthase phosphorylation and cGMP level and increased PARP-1 activity in coronary arterioles from diabetic mice compared with control mice.
1315	22454481	Interestingly, PARP-1 inhibitors significantly reduced the potentiation of myogenic tone, improved endothelium-dependent relaxation, restored endothelial NO synthase phosphorylation and cGMP, and attenuated cleaved PARP-1.
1316	22454481	These results were supported by in vitro studies indicating that downregulation of PARP-1 in mesenteric resistance arteries using PARP-1 short hairpin RNA lentiviral particles significantly improved endothelium-dependent relaxation in mesenteric resistance arteries from diabetic mice compared with control mice.
1317	22454481	The inhibition of NO synthesis by N(G)-nitro-L-arginine methyl ester (L-NAME) significantly reduced the endothelium-dependent relaxation in coronary arterioles and mesenteric resistance arteries from control and diabetic mice treated with PARP-1 inhibitors and PARP-1 short hairpin RNA lentiviral particles.
1318	22454481	In addition, we demonstrated that enhanced cleaved PARP-1, its binding to DNA, and DNA damage were reduced after PARP-1 inhibition in cultured endothelial cells stimulated with high glucose.
1319	22454481	We provide evidence that T2DM impairs microvascular function by an enhanced PARP-1 activity-dependent mechanism.
1320	22454481	Therefore, PARP-1 could be a potential target for overcoming diabetic microvascular complications.
1321	22454481	We hypothesized that increased poly(ADP-ribose) polymerase 1 (PARP-1) activity contributes to microvascular dysfunction in T2DM.
1322	22454481	T2DM (db(-)/db(-)) and nondiabetic control (db(-)/db(+)) mice were treated with 2 different PARP-1 inhibitors (INO-1001, 5 mg/kg per day and ABT-888, 15 mg/kg per day) for 2 weeks.
1323	22454481	These results were associated with decreased endothelial NO synthase phosphorylation and cGMP level and increased PARP-1 activity in coronary arterioles from diabetic mice compared with control mice.
1324	22454481	Interestingly, PARP-1 inhibitors significantly reduced the potentiation of myogenic tone, improved endothelium-dependent relaxation, restored endothelial NO synthase phosphorylation and cGMP, and attenuated cleaved PARP-1.
1325	22454481	These results were supported by in vitro studies indicating that downregulation of PARP-1 in mesenteric resistance arteries using PARP-1 short hairpin RNA lentiviral particles significantly improved endothelium-dependent relaxation in mesenteric resistance arteries from diabetic mice compared with control mice.
1326	22454481	The inhibition of NO synthesis by N(G)-nitro-L-arginine methyl ester (L-NAME) significantly reduced the endothelium-dependent relaxation in coronary arterioles and mesenteric resistance arteries from control and diabetic mice treated with PARP-1 inhibitors and PARP-1 short hairpin RNA lentiviral particles.
1327	22454481	In addition, we demonstrated that enhanced cleaved PARP-1, its binding to DNA, and DNA damage were reduced after PARP-1 inhibition in cultured endothelial cells stimulated with high glucose.
1328	22454481	We provide evidence that T2DM impairs microvascular function by an enhanced PARP-1 activity-dependent mechanism.
1329	22454481	Therefore, PARP-1 could be a potential target for overcoming diabetic microvascular complications.
1330	22454481	We hypothesized that increased poly(ADP-ribose) polymerase 1 (PARP-1) activity contributes to microvascular dysfunction in T2DM.
1331	22454481	T2DM (db(-)/db(-)) and nondiabetic control (db(-)/db(+)) mice were treated with 2 different PARP-1 inhibitors (INO-1001, 5 mg/kg per day and ABT-888, 15 mg/kg per day) for 2 weeks.
1332	22454481	These results were associated with decreased endothelial NO synthase phosphorylation and cGMP level and increased PARP-1 activity in coronary arterioles from diabetic mice compared with control mice.
1333	22454481	Interestingly, PARP-1 inhibitors significantly reduced the potentiation of myogenic tone, improved endothelium-dependent relaxation, restored endothelial NO synthase phosphorylation and cGMP, and attenuated cleaved PARP-1.
1334	22454481	These results were supported by in vitro studies indicating that downregulation of PARP-1 in mesenteric resistance arteries using PARP-1 short hairpin RNA lentiviral particles significantly improved endothelium-dependent relaxation in mesenteric resistance arteries from diabetic mice compared with control mice.
1335	22454481	The inhibition of NO synthesis by N(G)-nitro-L-arginine methyl ester (L-NAME) significantly reduced the endothelium-dependent relaxation in coronary arterioles and mesenteric resistance arteries from control and diabetic mice treated with PARP-1 inhibitors and PARP-1 short hairpin RNA lentiviral particles.
1336	22454481	In addition, we demonstrated that enhanced cleaved PARP-1, its binding to DNA, and DNA damage were reduced after PARP-1 inhibition in cultured endothelial cells stimulated with high glucose.
1337	22454481	We provide evidence that T2DM impairs microvascular function by an enhanced PARP-1 activity-dependent mechanism.
1338	22454481	Therefore, PARP-1 could be a potential target for overcoming diabetic microvascular complications.
1339	22454481	We hypothesized that increased poly(ADP-ribose) polymerase 1 (PARP-1) activity contributes to microvascular dysfunction in T2DM.
1340	22454481	T2DM (db(-)/db(-)) and nondiabetic control (db(-)/db(+)) mice were treated with 2 different PARP-1 inhibitors (INO-1001, 5 mg/kg per day and ABT-888, 15 mg/kg per day) for 2 weeks.
1341	22454481	These results were associated with decreased endothelial NO synthase phosphorylation and cGMP level and increased PARP-1 activity in coronary arterioles from diabetic mice compared with control mice.
1342	22454481	Interestingly, PARP-1 inhibitors significantly reduced the potentiation of myogenic tone, improved endothelium-dependent relaxation, restored endothelial NO synthase phosphorylation and cGMP, and attenuated cleaved PARP-1.
1343	22454481	These results were supported by in vitro studies indicating that downregulation of PARP-1 in mesenteric resistance arteries using PARP-1 short hairpin RNA lentiviral particles significantly improved endothelium-dependent relaxation in mesenteric resistance arteries from diabetic mice compared with control mice.
1344	22454481	The inhibition of NO synthesis by N(G)-nitro-L-arginine methyl ester (L-NAME) significantly reduced the endothelium-dependent relaxation in coronary arterioles and mesenteric resistance arteries from control and diabetic mice treated with PARP-1 inhibitors and PARP-1 short hairpin RNA lentiviral particles.
1345	22454481	In addition, we demonstrated that enhanced cleaved PARP-1, its binding to DNA, and DNA damage were reduced after PARP-1 inhibition in cultured endothelial cells stimulated with high glucose.
1346	22454481	We provide evidence that T2DM impairs microvascular function by an enhanced PARP-1 activity-dependent mechanism.
1347	22454481	Therefore, PARP-1 could be a potential target for overcoming diabetic microvascular complications.
1348	22454481	We hypothesized that increased poly(ADP-ribose) polymerase 1 (PARP-1) activity contributes to microvascular dysfunction in T2DM.
1349	22454481	T2DM (db(-)/db(-)) and nondiabetic control (db(-)/db(+)) mice were treated with 2 different PARP-1 inhibitors (INO-1001, 5 mg/kg per day and ABT-888, 15 mg/kg per day) for 2 weeks.
1350	22454481	These results were associated with decreased endothelial NO synthase phosphorylation and cGMP level and increased PARP-1 activity in coronary arterioles from diabetic mice compared with control mice.
1351	22454481	Interestingly, PARP-1 inhibitors significantly reduced the potentiation of myogenic tone, improved endothelium-dependent relaxation, restored endothelial NO synthase phosphorylation and cGMP, and attenuated cleaved PARP-1.
1352	22454481	These results were supported by in vitro studies indicating that downregulation of PARP-1 in mesenteric resistance arteries using PARP-1 short hairpin RNA lentiviral particles significantly improved endothelium-dependent relaxation in mesenteric resistance arteries from diabetic mice compared with control mice.
1353	22454481	The inhibition of NO synthesis by N(G)-nitro-L-arginine methyl ester (L-NAME) significantly reduced the endothelium-dependent relaxation in coronary arterioles and mesenteric resistance arteries from control and diabetic mice treated with PARP-1 inhibitors and PARP-1 short hairpin RNA lentiviral particles.
1354	22454481	In addition, we demonstrated that enhanced cleaved PARP-1, its binding to DNA, and DNA damage were reduced after PARP-1 inhibition in cultured endothelial cells stimulated with high glucose.
1355	22454481	We provide evidence that T2DM impairs microvascular function by an enhanced PARP-1 activity-dependent mechanism.
1356	22454481	Therefore, PARP-1 could be a potential target for overcoming diabetic microvascular complications.
1357	22454481	We hypothesized that increased poly(ADP-ribose) polymerase 1 (PARP-1) activity contributes to microvascular dysfunction in T2DM.
1358	22454481	T2DM (db(-)/db(-)) and nondiabetic control (db(-)/db(+)) mice were treated with 2 different PARP-1 inhibitors (INO-1001, 5 mg/kg per day and ABT-888, 15 mg/kg per day) for 2 weeks.
1359	22454481	These results were associated with decreased endothelial NO synthase phosphorylation and cGMP level and increased PARP-1 activity in coronary arterioles from diabetic mice compared with control mice.
1360	22454481	Interestingly, PARP-1 inhibitors significantly reduced the potentiation of myogenic tone, improved endothelium-dependent relaxation, restored endothelial NO synthase phosphorylation and cGMP, and attenuated cleaved PARP-1.
1361	22454481	These results were supported by in vitro studies indicating that downregulation of PARP-1 in mesenteric resistance arteries using PARP-1 short hairpin RNA lentiviral particles significantly improved endothelium-dependent relaxation in mesenteric resistance arteries from diabetic mice compared with control mice.
1362	22454481	The inhibition of NO synthesis by N(G)-nitro-L-arginine methyl ester (L-NAME) significantly reduced the endothelium-dependent relaxation in coronary arterioles and mesenteric resistance arteries from control and diabetic mice treated with PARP-1 inhibitors and PARP-1 short hairpin RNA lentiviral particles.
1363	22454481	In addition, we demonstrated that enhanced cleaved PARP-1, its binding to DNA, and DNA damage were reduced after PARP-1 inhibition in cultured endothelial cells stimulated with high glucose.
1364	22454481	We provide evidence that T2DM impairs microvascular function by an enhanced PARP-1 activity-dependent mechanism.
1365	22454481	Therefore, PARP-1 could be a potential target for overcoming diabetic microvascular complications.
1366	22454481	We hypothesized that increased poly(ADP-ribose) polymerase 1 (PARP-1) activity contributes to microvascular dysfunction in T2DM.
1367	22454481	T2DM (db(-)/db(-)) and nondiabetic control (db(-)/db(+)) mice were treated with 2 different PARP-1 inhibitors (INO-1001, 5 mg/kg per day and ABT-888, 15 mg/kg per day) for 2 weeks.
1368	22454481	These results were associated with decreased endothelial NO synthase phosphorylation and cGMP level and increased PARP-1 activity in coronary arterioles from diabetic mice compared with control mice.
1369	22454481	Interestingly, PARP-1 inhibitors significantly reduced the potentiation of myogenic tone, improved endothelium-dependent relaxation, restored endothelial NO synthase phosphorylation and cGMP, and attenuated cleaved PARP-1.
1370	22454481	These results were supported by in vitro studies indicating that downregulation of PARP-1 in mesenteric resistance arteries using PARP-1 short hairpin RNA lentiviral particles significantly improved endothelium-dependent relaxation in mesenteric resistance arteries from diabetic mice compared with control mice.
1371	22454481	The inhibition of NO synthesis by N(G)-nitro-L-arginine methyl ester (L-NAME) significantly reduced the endothelium-dependent relaxation in coronary arterioles and mesenteric resistance arteries from control and diabetic mice treated with PARP-1 inhibitors and PARP-1 short hairpin RNA lentiviral particles.
1372	22454481	In addition, we demonstrated that enhanced cleaved PARP-1, its binding to DNA, and DNA damage were reduced after PARP-1 inhibition in cultured endothelial cells stimulated with high glucose.
1373	22454481	We provide evidence that T2DM impairs microvascular function by an enhanced PARP-1 activity-dependent mechanism.
1374	22454481	Therefore, PARP-1 could be a potential target for overcoming diabetic microvascular complications.
1375	22454481	We hypothesized that increased poly(ADP-ribose) polymerase 1 (PARP-1) activity contributes to microvascular dysfunction in T2DM.
1376	22454481	T2DM (db(-)/db(-)) and nondiabetic control (db(-)/db(+)) mice were treated with 2 different PARP-1 inhibitors (INO-1001, 5 mg/kg per day and ABT-888, 15 mg/kg per day) for 2 weeks.
1377	22454481	These results were associated with decreased endothelial NO synthase phosphorylation and cGMP level and increased PARP-1 activity in coronary arterioles from diabetic mice compared with control mice.
1378	22454481	Interestingly, PARP-1 inhibitors significantly reduced the potentiation of myogenic tone, improved endothelium-dependent relaxation, restored endothelial NO synthase phosphorylation and cGMP, and attenuated cleaved PARP-1.
1379	22454481	These results were supported by in vitro studies indicating that downregulation of PARP-1 in mesenteric resistance arteries using PARP-1 short hairpin RNA lentiviral particles significantly improved endothelium-dependent relaxation in mesenteric resistance arteries from diabetic mice compared with control mice.
1380	22454481	The inhibition of NO synthesis by N(G)-nitro-L-arginine methyl ester (L-NAME) significantly reduced the endothelium-dependent relaxation in coronary arterioles and mesenteric resistance arteries from control and diabetic mice treated with PARP-1 inhibitors and PARP-1 short hairpin RNA lentiviral particles.
1381	22454481	In addition, we demonstrated that enhanced cleaved PARP-1, its binding to DNA, and DNA damage were reduced after PARP-1 inhibition in cultured endothelial cells stimulated with high glucose.
1382	22454481	We provide evidence that T2DM impairs microvascular function by an enhanced PARP-1 activity-dependent mechanism.
1383	22454481	Therefore, PARP-1 could be a potential target for overcoming diabetic microvascular complications.
1384	22454481	We hypothesized that increased poly(ADP-ribose) polymerase 1 (PARP-1) activity contributes to microvascular dysfunction in T2DM.
1385	22454481	T2DM (db(-)/db(-)) and nondiabetic control (db(-)/db(+)) mice were treated with 2 different PARP-1 inhibitors (INO-1001, 5 mg/kg per day and ABT-888, 15 mg/kg per day) for 2 weeks.
1386	22454481	These results were associated with decreased endothelial NO synthase phosphorylation and cGMP level and increased PARP-1 activity in coronary arterioles from diabetic mice compared with control mice.
1387	22454481	Interestingly, PARP-1 inhibitors significantly reduced the potentiation of myogenic tone, improved endothelium-dependent relaxation, restored endothelial NO synthase phosphorylation and cGMP, and attenuated cleaved PARP-1.
1388	22454481	These results were supported by in vitro studies indicating that downregulation of PARP-1 in mesenteric resistance arteries using PARP-1 short hairpin RNA lentiviral particles significantly improved endothelium-dependent relaxation in mesenteric resistance arteries from diabetic mice compared with control mice.
1389	22454481	The inhibition of NO synthesis by N(G)-nitro-L-arginine methyl ester (L-NAME) significantly reduced the endothelium-dependent relaxation in coronary arterioles and mesenteric resistance arteries from control and diabetic mice treated with PARP-1 inhibitors and PARP-1 short hairpin RNA lentiviral particles.
1390	22454481	In addition, we demonstrated that enhanced cleaved PARP-1, its binding to DNA, and DNA damage were reduced after PARP-1 inhibition in cultured endothelial cells stimulated with high glucose.
1391	22454481	We provide evidence that T2DM impairs microvascular function by an enhanced PARP-1 activity-dependent mechanism.
1392	22454481	Therefore, PARP-1 could be a potential target for overcoming diabetic microvascular complications.
1393	22476980	PARP-1 is responsible for more than 90 % of protein poly-ADP-ribosylation in the brain and may play a role as a molecular switch for cell survival and death.
1394	22476980	The functional roles of PARP-1 are largely mediated by its activation after binding to damaged DNA.
1395	22476980	Upon binding, PARP-1 activity increases rapidly and cleaves NAD(+) into ADP-ribose and nicotinamide.
1396	22476980	Increased activity of PARP-1 can promote DNA repair and its interaction with several transcription factors, whereas hyperactivation of PARP-1 can result in poly(ADP-ribose) accumulation and depletion of NAD(+) and ATP which may lead to caspase independent apoptotic or necrotic cell death, respectively.
1397	22476980	Excessive PARP-1 activity has been implicated in the pathogenesis of numerous clinical conditions such as stroke, myocardial infarction, inflammation, diabetes, and neurodegenerative disorders.
1398	22476980	Therefore, it is not surprising that the search for PARP-1 inhibitors with specific therapeutic uses (e.g., brain ischemia, cancer) has been an active area of research.
1399	22476980	Beyond medicinal uses, naturally occurring PARP-1 inhibitors may also offer a unique preventative means at attenuating chronic inflammatory diseases through dietary supplementation.
1400	22476980	This possibility has prompted research for specific, naturally occurring inhibitors of PARP-1.
1401	22476980	Though fewer investigations focus on identifying endogenous inhibitors/modulators of PARP-1 activity in vivo, these activities are very important for better understanding the complex regulation of this enzyme and the potential long-term benefits of supplementation with PARP-1 inhibitors.
1402	22476980	With this in mind, the focus of this article will be on providing a state-of-the-science review on endogenous and naturally occurring compounds that inhibit PARP-1.
1403	22476980	PARP-1 is responsible for more than 90 % of protein poly-ADP-ribosylation in the brain and may play a role as a molecular switch for cell survival and death.
1404	22476980	The functional roles of PARP-1 are largely mediated by its activation after binding to damaged DNA.
1405	22476980	Upon binding, PARP-1 activity increases rapidly and cleaves NAD(+) into ADP-ribose and nicotinamide.
1406	22476980	Increased activity of PARP-1 can promote DNA repair and its interaction with several transcription factors, whereas hyperactivation of PARP-1 can result in poly(ADP-ribose) accumulation and depletion of NAD(+) and ATP which may lead to caspase independent apoptotic or necrotic cell death, respectively.
1407	22476980	Excessive PARP-1 activity has been implicated in the pathogenesis of numerous clinical conditions such as stroke, myocardial infarction, inflammation, diabetes, and neurodegenerative disorders.
1408	22476980	Therefore, it is not surprising that the search for PARP-1 inhibitors with specific therapeutic uses (e.g., brain ischemia, cancer) has been an active area of research.
1409	22476980	Beyond medicinal uses, naturally occurring PARP-1 inhibitors may also offer a unique preventative means at attenuating chronic inflammatory diseases through dietary supplementation.
1410	22476980	This possibility has prompted research for specific, naturally occurring inhibitors of PARP-1.
1411	22476980	Though fewer investigations focus on identifying endogenous inhibitors/modulators of PARP-1 activity in vivo, these activities are very important for better understanding the complex regulation of this enzyme and the potential long-term benefits of supplementation with PARP-1 inhibitors.
1412	22476980	With this in mind, the focus of this article will be on providing a state-of-the-science review on endogenous and naturally occurring compounds that inhibit PARP-1.
1413	22476980	PARP-1 is responsible for more than 90 % of protein poly-ADP-ribosylation in the brain and may play a role as a molecular switch for cell survival and death.
1414	22476980	The functional roles of PARP-1 are largely mediated by its activation after binding to damaged DNA.
1415	22476980	Upon binding, PARP-1 activity increases rapidly and cleaves NAD(+) into ADP-ribose and nicotinamide.
1416	22476980	Increased activity of PARP-1 can promote DNA repair and its interaction with several transcription factors, whereas hyperactivation of PARP-1 can result in poly(ADP-ribose) accumulation and depletion of NAD(+) and ATP which may lead to caspase independent apoptotic or necrotic cell death, respectively.
1417	22476980	Excessive PARP-1 activity has been implicated in the pathogenesis of numerous clinical conditions such as stroke, myocardial infarction, inflammation, diabetes, and neurodegenerative disorders.
1418	22476980	Therefore, it is not surprising that the search for PARP-1 inhibitors with specific therapeutic uses (e.g., brain ischemia, cancer) has been an active area of research.
1419	22476980	Beyond medicinal uses, naturally occurring PARP-1 inhibitors may also offer a unique preventative means at attenuating chronic inflammatory diseases through dietary supplementation.
1420	22476980	This possibility has prompted research for specific, naturally occurring inhibitors of PARP-1.
1421	22476980	Though fewer investigations focus on identifying endogenous inhibitors/modulators of PARP-1 activity in vivo, these activities are very important for better understanding the complex regulation of this enzyme and the potential long-term benefits of supplementation with PARP-1 inhibitors.
1422	22476980	With this in mind, the focus of this article will be on providing a state-of-the-science review on endogenous and naturally occurring compounds that inhibit PARP-1.
1423	22476980	PARP-1 is responsible for more than 90 % of protein poly-ADP-ribosylation in the brain and may play a role as a molecular switch for cell survival and death.
1424	22476980	The functional roles of PARP-1 are largely mediated by its activation after binding to damaged DNA.
1425	22476980	Upon binding, PARP-1 activity increases rapidly and cleaves NAD(+) into ADP-ribose and nicotinamide.
1426	22476980	Increased activity of PARP-1 can promote DNA repair and its interaction with several transcription factors, whereas hyperactivation of PARP-1 can result in poly(ADP-ribose) accumulation and depletion of NAD(+) and ATP which may lead to caspase independent apoptotic or necrotic cell death, respectively.
1427	22476980	Excessive PARP-1 activity has been implicated in the pathogenesis of numerous clinical conditions such as stroke, myocardial infarction, inflammation, diabetes, and neurodegenerative disorders.
1428	22476980	Therefore, it is not surprising that the search for PARP-1 inhibitors with specific therapeutic uses (e.g., brain ischemia, cancer) has been an active area of research.
1429	22476980	Beyond medicinal uses, naturally occurring PARP-1 inhibitors may also offer a unique preventative means at attenuating chronic inflammatory diseases through dietary supplementation.
1430	22476980	This possibility has prompted research for specific, naturally occurring inhibitors of PARP-1.
1431	22476980	Though fewer investigations focus on identifying endogenous inhibitors/modulators of PARP-1 activity in vivo, these activities are very important for better understanding the complex regulation of this enzyme and the potential long-term benefits of supplementation with PARP-1 inhibitors.
1432	22476980	With this in mind, the focus of this article will be on providing a state-of-the-science review on endogenous and naturally occurring compounds that inhibit PARP-1.
1433	22476980	PARP-1 is responsible for more than 90 % of protein poly-ADP-ribosylation in the brain and may play a role as a molecular switch for cell survival and death.
1434	22476980	The functional roles of PARP-1 are largely mediated by its activation after binding to damaged DNA.
1435	22476980	Upon binding, PARP-1 activity increases rapidly and cleaves NAD(+) into ADP-ribose and nicotinamide.
1436	22476980	Increased activity of PARP-1 can promote DNA repair and its interaction with several transcription factors, whereas hyperactivation of PARP-1 can result in poly(ADP-ribose) accumulation and depletion of NAD(+) and ATP which may lead to caspase independent apoptotic or necrotic cell death, respectively.
1437	22476980	Excessive PARP-1 activity has been implicated in the pathogenesis of numerous clinical conditions such as stroke, myocardial infarction, inflammation, diabetes, and neurodegenerative disorders.
1438	22476980	Therefore, it is not surprising that the search for PARP-1 inhibitors with specific therapeutic uses (e.g., brain ischemia, cancer) has been an active area of research.
1439	22476980	Beyond medicinal uses, naturally occurring PARP-1 inhibitors may also offer a unique preventative means at attenuating chronic inflammatory diseases through dietary supplementation.
1440	22476980	This possibility has prompted research for specific, naturally occurring inhibitors of PARP-1.
1441	22476980	Though fewer investigations focus on identifying endogenous inhibitors/modulators of PARP-1 activity in vivo, these activities are very important for better understanding the complex regulation of this enzyme and the potential long-term benefits of supplementation with PARP-1 inhibitors.
1442	22476980	With this in mind, the focus of this article will be on providing a state-of-the-science review on endogenous and naturally occurring compounds that inhibit PARP-1.
1443	22476980	PARP-1 is responsible for more than 90 % of protein poly-ADP-ribosylation in the brain and may play a role as a molecular switch for cell survival and death.
1444	22476980	The functional roles of PARP-1 are largely mediated by its activation after binding to damaged DNA.
1445	22476980	Upon binding, PARP-1 activity increases rapidly and cleaves NAD(+) into ADP-ribose and nicotinamide.
1446	22476980	Increased activity of PARP-1 can promote DNA repair and its interaction with several transcription factors, whereas hyperactivation of PARP-1 can result in poly(ADP-ribose) accumulation and depletion of NAD(+) and ATP which may lead to caspase independent apoptotic or necrotic cell death, respectively.
1447	22476980	Excessive PARP-1 activity has been implicated in the pathogenesis of numerous clinical conditions such as stroke, myocardial infarction, inflammation, diabetes, and neurodegenerative disorders.
1448	22476980	Therefore, it is not surprising that the search for PARP-1 inhibitors with specific therapeutic uses (e.g., brain ischemia, cancer) has been an active area of research.
1449	22476980	Beyond medicinal uses, naturally occurring PARP-1 inhibitors may also offer a unique preventative means at attenuating chronic inflammatory diseases through dietary supplementation.
1450	22476980	This possibility has prompted research for specific, naturally occurring inhibitors of PARP-1.
1451	22476980	Though fewer investigations focus on identifying endogenous inhibitors/modulators of PARP-1 activity in vivo, these activities are very important for better understanding the complex regulation of this enzyme and the potential long-term benefits of supplementation with PARP-1 inhibitors.
1452	22476980	With this in mind, the focus of this article will be on providing a state-of-the-science review on endogenous and naturally occurring compounds that inhibit PARP-1.
1453	22476980	PARP-1 is responsible for more than 90 % of protein poly-ADP-ribosylation in the brain and may play a role as a molecular switch for cell survival and death.
1454	22476980	The functional roles of PARP-1 are largely mediated by its activation after binding to damaged DNA.
1455	22476980	Upon binding, PARP-1 activity increases rapidly and cleaves NAD(+) into ADP-ribose and nicotinamide.
1456	22476980	Increased activity of PARP-1 can promote DNA repair and its interaction with several transcription factors, whereas hyperactivation of PARP-1 can result in poly(ADP-ribose) accumulation and depletion of NAD(+) and ATP which may lead to caspase independent apoptotic or necrotic cell death, respectively.
1457	22476980	Excessive PARP-1 activity has been implicated in the pathogenesis of numerous clinical conditions such as stroke, myocardial infarction, inflammation, diabetes, and neurodegenerative disorders.
1458	22476980	Therefore, it is not surprising that the search for PARP-1 inhibitors with specific therapeutic uses (e.g., brain ischemia, cancer) has been an active area of research.
1459	22476980	Beyond medicinal uses, naturally occurring PARP-1 inhibitors may also offer a unique preventative means at attenuating chronic inflammatory diseases through dietary supplementation.
1460	22476980	This possibility has prompted research for specific, naturally occurring inhibitors of PARP-1.
1461	22476980	Though fewer investigations focus on identifying endogenous inhibitors/modulators of PARP-1 activity in vivo, these activities are very important for better understanding the complex regulation of this enzyme and the potential long-term benefits of supplementation with PARP-1 inhibitors.
1462	22476980	With this in mind, the focus of this article will be on providing a state-of-the-science review on endogenous and naturally occurring compounds that inhibit PARP-1.
1463	22476980	PARP-1 is responsible for more than 90 % of protein poly-ADP-ribosylation in the brain and may play a role as a molecular switch for cell survival and death.
1464	22476980	The functional roles of PARP-1 are largely mediated by its activation after binding to damaged DNA.
1465	22476980	Upon binding, PARP-1 activity increases rapidly and cleaves NAD(+) into ADP-ribose and nicotinamide.
1466	22476980	Increased activity of PARP-1 can promote DNA repair and its interaction with several transcription factors, whereas hyperactivation of PARP-1 can result in poly(ADP-ribose) accumulation and depletion of NAD(+) and ATP which may lead to caspase independent apoptotic or necrotic cell death, respectively.
1467	22476980	Excessive PARP-1 activity has been implicated in the pathogenesis of numerous clinical conditions such as stroke, myocardial infarction, inflammation, diabetes, and neurodegenerative disorders.
1468	22476980	Therefore, it is not surprising that the search for PARP-1 inhibitors with specific therapeutic uses (e.g., brain ischemia, cancer) has been an active area of research.
1469	22476980	Beyond medicinal uses, naturally occurring PARP-1 inhibitors may also offer a unique preventative means at attenuating chronic inflammatory diseases through dietary supplementation.
1470	22476980	This possibility has prompted research for specific, naturally occurring inhibitors of PARP-1.
1471	22476980	Though fewer investigations focus on identifying endogenous inhibitors/modulators of PARP-1 activity in vivo, these activities are very important for better understanding the complex regulation of this enzyme and the potential long-term benefits of supplementation with PARP-1 inhibitors.
1472	22476980	With this in mind, the focus of this article will be on providing a state-of-the-science review on endogenous and naturally occurring compounds that inhibit PARP-1.
1473	22476980	PARP-1 is responsible for more than 90 % of protein poly-ADP-ribosylation in the brain and may play a role as a molecular switch for cell survival and death.
1474	22476980	The functional roles of PARP-1 are largely mediated by its activation after binding to damaged DNA.
1475	22476980	Upon binding, PARP-1 activity increases rapidly and cleaves NAD(+) into ADP-ribose and nicotinamide.
1476	22476980	Increased activity of PARP-1 can promote DNA repair and its interaction with several transcription factors, whereas hyperactivation of PARP-1 can result in poly(ADP-ribose) accumulation and depletion of NAD(+) and ATP which may lead to caspase independent apoptotic or necrotic cell death, respectively.
1477	22476980	Excessive PARP-1 activity has been implicated in the pathogenesis of numerous clinical conditions such as stroke, myocardial infarction, inflammation, diabetes, and neurodegenerative disorders.
1478	22476980	Therefore, it is not surprising that the search for PARP-1 inhibitors with specific therapeutic uses (e.g., brain ischemia, cancer) has been an active area of research.
1479	22476980	Beyond medicinal uses, naturally occurring PARP-1 inhibitors may also offer a unique preventative means at attenuating chronic inflammatory diseases through dietary supplementation.
1480	22476980	This possibility has prompted research for specific, naturally occurring inhibitors of PARP-1.
1481	22476980	Though fewer investigations focus on identifying endogenous inhibitors/modulators of PARP-1 activity in vivo, these activities are very important for better understanding the complex regulation of this enzyme and the potential long-term benefits of supplementation with PARP-1 inhibitors.
1482	22476980	With this in mind, the focus of this article will be on providing a state-of-the-science review on endogenous and naturally occurring compounds that inhibit PARP-1.
1483	22476980	PARP-1 is responsible for more than 90 % of protein poly-ADP-ribosylation in the brain and may play a role as a molecular switch for cell survival and death.
1484	22476980	The functional roles of PARP-1 are largely mediated by its activation after binding to damaged DNA.
1485	22476980	Upon binding, PARP-1 activity increases rapidly and cleaves NAD(+) into ADP-ribose and nicotinamide.
1486	22476980	Increased activity of PARP-1 can promote DNA repair and its interaction with several transcription factors, whereas hyperactivation of PARP-1 can result in poly(ADP-ribose) accumulation and depletion of NAD(+) and ATP which may lead to caspase independent apoptotic or necrotic cell death, respectively.
1487	22476980	Excessive PARP-1 activity has been implicated in the pathogenesis of numerous clinical conditions such as stroke, myocardial infarction, inflammation, diabetes, and neurodegenerative disorders.
1488	22476980	Therefore, it is not surprising that the search for PARP-1 inhibitors with specific therapeutic uses (e.g., brain ischemia, cancer) has been an active area of research.
1489	22476980	Beyond medicinal uses, naturally occurring PARP-1 inhibitors may also offer a unique preventative means at attenuating chronic inflammatory diseases through dietary supplementation.
1490	22476980	This possibility has prompted research for specific, naturally occurring inhibitors of PARP-1.
1491	22476980	Though fewer investigations focus on identifying endogenous inhibitors/modulators of PARP-1 activity in vivo, these activities are very important for better understanding the complex regulation of this enzyme and the potential long-term benefits of supplementation with PARP-1 inhibitors.
1492	22476980	With this in mind, the focus of this article will be on providing a state-of-the-science review on endogenous and naturally occurring compounds that inhibit PARP-1.
1493	22535743	Cytokine-mediated β-cell damage in PARP-1-deficient islets.
1494	22535743	In mice, the deletion of PARP-1 attenuates tissue injury in a number of animal models of human disease, including streptozotocin-induced diabetes.
1495	22535743	Also, inflammatory cell signaling and inflammatory gene expression are attenuated in macrophages isolated from endotoxin-treated PARP-1-deficient mice.
1496	22535743	In this study, the effects of PARP-1 deletion on cytokine-mediated β-cell damage and macrophage activation were evaluated.
1497	22535743	There are no defects in inflammatory mediator signaling or inflammatory gene expression in macrophages and islets isolated from PARP-1-deficient mice.
1498	22535743	While PARP-1 deficiency protects islets against cytokine-induced islet cell death as measured by biochemical assays of membrane polarization, the genetic absence of PARP-1 does not effect cytokine-induced inhibition of insulin secretion or cytokine-induced DNA damage in islets.
1499	22535743	While PARP-1 deficiency appears to provide protection from cell death, it fails to provide protection against the inhibitory actions of cytokines on insulin secretion or the damaging actions on islet DNA integrity.
1500	22535743	Cytokine-mediated β-cell damage in PARP-1-deficient islets.
1501	22535743	In mice, the deletion of PARP-1 attenuates tissue injury in a number of animal models of human disease, including streptozotocin-induced diabetes.
1502	22535743	Also, inflammatory cell signaling and inflammatory gene expression are attenuated in macrophages isolated from endotoxin-treated PARP-1-deficient mice.
1503	22535743	In this study, the effects of PARP-1 deletion on cytokine-mediated β-cell damage and macrophage activation were evaluated.
1504	22535743	There are no defects in inflammatory mediator signaling or inflammatory gene expression in macrophages and islets isolated from PARP-1-deficient mice.
1505	22535743	While PARP-1 deficiency protects islets against cytokine-induced islet cell death as measured by biochemical assays of membrane polarization, the genetic absence of PARP-1 does not effect cytokine-induced inhibition of insulin secretion or cytokine-induced DNA damage in islets.
1506	22535743	While PARP-1 deficiency appears to provide protection from cell death, it fails to provide protection against the inhibitory actions of cytokines on insulin secretion or the damaging actions on islet DNA integrity.
1507	22535743	Cytokine-mediated β-cell damage in PARP-1-deficient islets.
1508	22535743	In mice, the deletion of PARP-1 attenuates tissue injury in a number of animal models of human disease, including streptozotocin-induced diabetes.
1509	22535743	Also, inflammatory cell signaling and inflammatory gene expression are attenuated in macrophages isolated from endotoxin-treated PARP-1-deficient mice.
1510	22535743	In this study, the effects of PARP-1 deletion on cytokine-mediated β-cell damage and macrophage activation were evaluated.
1511	22535743	There are no defects in inflammatory mediator signaling or inflammatory gene expression in macrophages and islets isolated from PARP-1-deficient mice.
1512	22535743	While PARP-1 deficiency protects islets against cytokine-induced islet cell death as measured by biochemical assays of membrane polarization, the genetic absence of PARP-1 does not effect cytokine-induced inhibition of insulin secretion or cytokine-induced DNA damage in islets.
1513	22535743	While PARP-1 deficiency appears to provide protection from cell death, it fails to provide protection against the inhibitory actions of cytokines on insulin secretion or the damaging actions on islet DNA integrity.
1514	22535743	Cytokine-mediated β-cell damage in PARP-1-deficient islets.
1515	22535743	In mice, the deletion of PARP-1 attenuates tissue injury in a number of animal models of human disease, including streptozotocin-induced diabetes.
1516	22535743	Also, inflammatory cell signaling and inflammatory gene expression are attenuated in macrophages isolated from endotoxin-treated PARP-1-deficient mice.
1517	22535743	In this study, the effects of PARP-1 deletion on cytokine-mediated β-cell damage and macrophage activation were evaluated.
1518	22535743	There are no defects in inflammatory mediator signaling or inflammatory gene expression in macrophages and islets isolated from PARP-1-deficient mice.
1519	22535743	While PARP-1 deficiency protects islets against cytokine-induced islet cell death as measured by biochemical assays of membrane polarization, the genetic absence of PARP-1 does not effect cytokine-induced inhibition of insulin secretion or cytokine-induced DNA damage in islets.
1520	22535743	While PARP-1 deficiency appears to provide protection from cell death, it fails to provide protection against the inhibitory actions of cytokines on insulin secretion or the damaging actions on islet DNA integrity.
1521	22535743	Cytokine-mediated β-cell damage in PARP-1-deficient islets.
1522	22535743	In mice, the deletion of PARP-1 attenuates tissue injury in a number of animal models of human disease, including streptozotocin-induced diabetes.
1523	22535743	Also, inflammatory cell signaling and inflammatory gene expression are attenuated in macrophages isolated from endotoxin-treated PARP-1-deficient mice.
1524	22535743	In this study, the effects of PARP-1 deletion on cytokine-mediated β-cell damage and macrophage activation were evaluated.
1525	22535743	There are no defects in inflammatory mediator signaling or inflammatory gene expression in macrophages and islets isolated from PARP-1-deficient mice.
1526	22535743	While PARP-1 deficiency protects islets against cytokine-induced islet cell death as measured by biochemical assays of membrane polarization, the genetic absence of PARP-1 does not effect cytokine-induced inhibition of insulin secretion or cytokine-induced DNA damage in islets.
1527	22535743	While PARP-1 deficiency appears to provide protection from cell death, it fails to provide protection against the inhibitory actions of cytokines on insulin secretion or the damaging actions on islet DNA integrity.
1528	22535743	Cytokine-mediated β-cell damage in PARP-1-deficient islets.
1529	22535743	In mice, the deletion of PARP-1 attenuates tissue injury in a number of animal models of human disease, including streptozotocin-induced diabetes.
1530	22535743	Also, inflammatory cell signaling and inflammatory gene expression are attenuated in macrophages isolated from endotoxin-treated PARP-1-deficient mice.
1531	22535743	In this study, the effects of PARP-1 deletion on cytokine-mediated β-cell damage and macrophage activation were evaluated.
1532	22535743	There are no defects in inflammatory mediator signaling or inflammatory gene expression in macrophages and islets isolated from PARP-1-deficient mice.
1533	22535743	While PARP-1 deficiency protects islets against cytokine-induced islet cell death as measured by biochemical assays of membrane polarization, the genetic absence of PARP-1 does not effect cytokine-induced inhibition of insulin secretion or cytokine-induced DNA damage in islets.
1534	22535743	While PARP-1 deficiency appears to provide protection from cell death, it fails to provide protection against the inhibitory actions of cytokines on insulin secretion or the damaging actions on islet DNA integrity.
1535	22535743	Cytokine-mediated β-cell damage in PARP-1-deficient islets.
1536	22535743	In mice, the deletion of PARP-1 attenuates tissue injury in a number of animal models of human disease, including streptozotocin-induced diabetes.
1537	22535743	Also, inflammatory cell signaling and inflammatory gene expression are attenuated in macrophages isolated from endotoxin-treated PARP-1-deficient mice.
1538	22535743	In this study, the effects of PARP-1 deletion on cytokine-mediated β-cell damage and macrophage activation were evaluated.
1539	22535743	There are no defects in inflammatory mediator signaling or inflammatory gene expression in macrophages and islets isolated from PARP-1-deficient mice.
1540	22535743	While PARP-1 deficiency protects islets against cytokine-induced islet cell death as measured by biochemical assays of membrane polarization, the genetic absence of PARP-1 does not effect cytokine-induced inhibition of insulin secretion or cytokine-induced DNA damage in islets.
1541	22535743	While PARP-1 deficiency appears to provide protection from cell death, it fails to provide protection against the inhibitory actions of cytokines on insulin secretion or the damaging actions on islet DNA integrity.
1542	22619373	STZ is transported into B-cells via the glucose transporter GLUT2 and causes DNA damage leading to increased activity of poly(ADP-ribose) polymerase (PARP-1) to repair DNA.
1543	22619373	The protective action of NA is due to the inhibition of PARP-1 activity.
1544	22619373	STZ is transported into B-cells via the glucose transporter GLUT2 and causes DNA damage leading to increased activity of poly(ADP-ribose) polymerase (PARP-1) to repair DNA.
1545	22619373	The protective action of NA is due to the inhibition of PARP-1 activity.
1546	22923475	Abnormalities characteristic of the early stages of retinopathy and allodynia were measured in chimeric mice lacking inducible nitric oxide synthase (iNOS) or poly(ADP-ribosyl) polymerase (PARP1) in only their marrow-derived cells.
1547	22923475	Diabetes-induced capillary degeneration, proinflammatory changes, and superoxide production in the retina and allodynia were inhibited in diabetic animals in which iNOS or PARP1 was deleted from bone marrow cells only.
1548	22923475	Immunodepletion of neutrophils or monocytes inhibited the endothelial death otherwise observed when coculturing leukocytes from wild-type diabetic animals with retinal endothelium. iNOS and PARP1 are known to play a role in inflammatory processes, and we conclude that proinflammatory processes within marrow-derived cells play a central role in the development of diabetes complications in the retina and nerve.
1549	22923475	Abnormalities characteristic of the early stages of retinopathy and allodynia were measured in chimeric mice lacking inducible nitric oxide synthase (iNOS) or poly(ADP-ribosyl) polymerase (PARP1) in only their marrow-derived cells.
1550	22923475	Diabetes-induced capillary degeneration, proinflammatory changes, and superoxide production in the retina and allodynia were inhibited in diabetic animals in which iNOS or PARP1 was deleted from bone marrow cells only.
1551	22923475	Immunodepletion of neutrophils or monocytes inhibited the endothelial death otherwise observed when coculturing leukocytes from wild-type diabetic animals with retinal endothelium. iNOS and PARP1 are known to play a role in inflammatory processes, and we conclude that proinflammatory processes within marrow-derived cells play a central role in the development of diabetes complications in the retina and nerve.
1552	22923475	Abnormalities characteristic of the early stages of retinopathy and allodynia were measured in chimeric mice lacking inducible nitric oxide synthase (iNOS) or poly(ADP-ribosyl) polymerase (PARP1) in only their marrow-derived cells.
1553	22923475	Diabetes-induced capillary degeneration, proinflammatory changes, and superoxide production in the retina and allodynia were inhibited in diabetic animals in which iNOS or PARP1 was deleted from bone marrow cells only.
1554	22923475	Immunodepletion of neutrophils or monocytes inhibited the endothelial death otherwise observed when coculturing leukocytes from wild-type diabetic animals with retinal endothelium. iNOS and PARP1 are known to play a role in inflammatory processes, and we conclude that proinflammatory processes within marrow-derived cells play a central role in the development of diabetes complications in the retina and nerve.
1555	22940604	Diabetes triggers a PARP1 mediated death pathway in the heart through participation of FoxO1.
1556	22940604	This was accompanied by a simultaneous increase in iNOS expression and iNOS induced protein nitrosylation of GAPDH, increased GAPDH binding to Siah1 and facilitated nuclear translocation of the complex.
1557	22940604	Even though caspase-3 was cleaved during diabetes, its nitrosylation modification affected its ability to inactivate PARP.
1558	22940604	As a result, there was PARP activation followed by nuclear compartmentalization of AIF, and increased phosphatidyl serine externalization.
1559	22940604	Our data suggests a role for FoxO1 mediated iNOS induced S-nitrosylation of target proteins like GAPDH and caspase-3 in initiating cardiac cell death following hyperglycemia, and could explain the impact of glycemic control in preventing cardiovascular disease in patients with diabetes.
1560	23040216	Relationship between NADPH oxidase p22phox C242T, PARP-1 Val762Ala polymorphisms, angiographically verified coronary artery disease and myocardial infarction in South Indian patients with type 2 diabetes mellitus.
1561	23349490	Enhanced NF-κB activity impairs vascular function through PARP-1-, SP-1-, and COX-2-dependent mechanisms in type 2 diabetes.
1562	23349490	The RNA levels for Sp-1 and eNOS phosphorylation were decreased, while p65NF-κB phosphorylation, cleaved poly(ADP-ribose) polymerase (PARP)-1, and cyclooxygenase (COX)-2 expression were increased in arteries from diabetic mice, which were restored after NF-κB inhibition and in db(-)/db(-p50NF-κB-/-) and db(-)/db(-PARP-1-/-) mice.
1563	23349490	In the current study, we provided evidence that enhanced NF-κB activity impairs vascular function by PARP-1-, Sp-1-, and COX-2-dependent mechanisms in male type 2 diabetic mice.
1564	23349490	Enhanced NF-κB activity impairs vascular function through PARP-1-, SP-1-, and COX-2-dependent mechanisms in type 2 diabetes.
1565	23349490	The RNA levels for Sp-1 and eNOS phosphorylation were decreased, while p65NF-κB phosphorylation, cleaved poly(ADP-ribose) polymerase (PARP)-1, and cyclooxygenase (COX)-2 expression were increased in arteries from diabetic mice, which were restored after NF-κB inhibition and in db(-)/db(-p50NF-κB-/-) and db(-)/db(-PARP-1-/-) mice.
1566	23349490	In the current study, we provided evidence that enhanced NF-κB activity impairs vascular function by PARP-1-, Sp-1-, and COX-2-dependent mechanisms in male type 2 diabetic mice.
1567	23349490	Enhanced NF-κB activity impairs vascular function through PARP-1-, SP-1-, and COX-2-dependent mechanisms in type 2 diabetes.
1568	23349490	The RNA levels for Sp-1 and eNOS phosphorylation were decreased, while p65NF-κB phosphorylation, cleaved poly(ADP-ribose) polymerase (PARP)-1, and cyclooxygenase (COX)-2 expression were increased in arteries from diabetic mice, which were restored after NF-κB inhibition and in db(-)/db(-p50NF-κB-/-) and db(-)/db(-PARP-1-/-) mice.
1569	23349490	In the current study, we provided evidence that enhanced NF-κB activity impairs vascular function by PARP-1-, Sp-1-, and COX-2-dependent mechanisms in male type 2 diabetic mice.
1570	23534291	The study was undertaken to investigate the influence of specific inhibitors of poly(ADP-ribose)polymerase-1 (PARP-1), in particular nicotinamide and 1,5-isoqinolinediol on white blood cells of rats with diabetes.
1571	23534291	Administration of PARP-1 inhibitors prevented the development of oxidative stress in leukocytes and increased their viability.
1572	23534291	Investigated PARP-1 inhibitors had no effect on the activity of superoxide dismutase and glucose levels in the blood.
1573	23534291	The study was undertaken to investigate the influence of specific inhibitors of poly(ADP-ribose)polymerase-1 (PARP-1), in particular nicotinamide and 1,5-isoqinolinediol on white blood cells of rats with diabetes.
1574	23534291	Administration of PARP-1 inhibitors prevented the development of oxidative stress in leukocytes and increased their viability.
1575	23534291	Investigated PARP-1 inhibitors had no effect on the activity of superoxide dismutase and glucose levels in the blood.
1576	23534291	The study was undertaken to investigate the influence of specific inhibitors of poly(ADP-ribose)polymerase-1 (PARP-1), in particular nicotinamide and 1,5-isoqinolinediol on white blood cells of rats with diabetes.
1577	23534291	Administration of PARP-1 inhibitors prevented the development of oxidative stress in leukocytes and increased their viability.
1578	23534291	Investigated PARP-1 inhibitors had no effect on the activity of superoxide dismutase and glucose levels in the blood.
1579	23555743	PARP-1 and YY1 are important novel regulators of CXCL12 gene transcription in rat pancreatic beta cells.
1580	23555743	The roles of poly(ADP-ribose) polymerase-1 (PARP-1) and transcription factor Yin Yang 1 (YY1) in Cxcl12 transcription were studied by examining their in vitro and in vivo binding affinities for the Cxcl12 promoter in a pancreatic beta cell line by the electrophoretic mobility shift assay and chromatin immunoprecipitation.
1581	23555743	The regulatory activities of PARP-1 and YY1 were assessed in transfection experiments using a reporter vector with a Cxcl12 promoter sequence driving luciferase gene expression.
1582	23555743	Experimental evidence for PARP-1 and YY1 revealed their trans-acting potential, wherein PARP-1 displayed an inhibitory, and YY1 a strong activating effect on Cxcl12 transcription.
1583	23555743	PARP-1 binding to the Cxcl12 promoter during basal and in STZ-compromised conditions led us to conclude that PARP-1 regulates constitutive Cxcl12 expression.
1584	23555743	During the early stage of oxidative stress, YY1 exhibited less affinity toward the Cxcl12 promoter while PARP-1 displayed strong binding.
1585	23555743	In the later stages of oxidative stress and intensive pancreatic beta cell injury, YY1 was highly expressed and firmly bound to Cxcl12 promoter in contrast to PARP-1.
1586	23555743	The observed ability of PARP-1 to downregulate, and of YY1 to upregulate Cxcl12 promoter activity anticipates corresponding effects in the natural context where the functional interplay of these proteins could finely balance Cxcl12 transcription.
1587	23555743	PARP-1 and YY1 are important novel regulators of CXCL12 gene transcription in rat pancreatic beta cells.
1588	23555743	The roles of poly(ADP-ribose) polymerase-1 (PARP-1) and transcription factor Yin Yang 1 (YY1) in Cxcl12 transcription were studied by examining their in vitro and in vivo binding affinities for the Cxcl12 promoter in a pancreatic beta cell line by the electrophoretic mobility shift assay and chromatin immunoprecipitation.
1589	23555743	The regulatory activities of PARP-1 and YY1 were assessed in transfection experiments using a reporter vector with a Cxcl12 promoter sequence driving luciferase gene expression.
1590	23555743	Experimental evidence for PARP-1 and YY1 revealed their trans-acting potential, wherein PARP-1 displayed an inhibitory, and YY1 a strong activating effect on Cxcl12 transcription.
1591	23555743	PARP-1 binding to the Cxcl12 promoter during basal and in STZ-compromised conditions led us to conclude that PARP-1 regulates constitutive Cxcl12 expression.
1592	23555743	During the early stage of oxidative stress, YY1 exhibited less affinity toward the Cxcl12 promoter while PARP-1 displayed strong binding.
1593	23555743	In the later stages of oxidative stress and intensive pancreatic beta cell injury, YY1 was highly expressed and firmly bound to Cxcl12 promoter in contrast to PARP-1.
1594	23555743	The observed ability of PARP-1 to downregulate, and of YY1 to upregulate Cxcl12 promoter activity anticipates corresponding effects in the natural context where the functional interplay of these proteins could finely balance Cxcl12 transcription.
1595	23555743	PARP-1 and YY1 are important novel regulators of CXCL12 gene transcription in rat pancreatic beta cells.
1596	23555743	The roles of poly(ADP-ribose) polymerase-1 (PARP-1) and transcription factor Yin Yang 1 (YY1) in Cxcl12 transcription were studied by examining their in vitro and in vivo binding affinities for the Cxcl12 promoter in a pancreatic beta cell line by the electrophoretic mobility shift assay and chromatin immunoprecipitation.
1597	23555743	The regulatory activities of PARP-1 and YY1 were assessed in transfection experiments using a reporter vector with a Cxcl12 promoter sequence driving luciferase gene expression.
1598	23555743	Experimental evidence for PARP-1 and YY1 revealed their trans-acting potential, wherein PARP-1 displayed an inhibitory, and YY1 a strong activating effect on Cxcl12 transcription.
1599	23555743	PARP-1 binding to the Cxcl12 promoter during basal and in STZ-compromised conditions led us to conclude that PARP-1 regulates constitutive Cxcl12 expression.
1600	23555743	During the early stage of oxidative stress, YY1 exhibited less affinity toward the Cxcl12 promoter while PARP-1 displayed strong binding.
1601	23555743	In the later stages of oxidative stress and intensive pancreatic beta cell injury, YY1 was highly expressed and firmly bound to Cxcl12 promoter in contrast to PARP-1.
1602	23555743	The observed ability of PARP-1 to downregulate, and of YY1 to upregulate Cxcl12 promoter activity anticipates corresponding effects in the natural context where the functional interplay of these proteins could finely balance Cxcl12 transcription.
1603	23555743	PARP-1 and YY1 are important novel regulators of CXCL12 gene transcription in rat pancreatic beta cells.
1604	23555743	The roles of poly(ADP-ribose) polymerase-1 (PARP-1) and transcription factor Yin Yang 1 (YY1) in Cxcl12 transcription were studied by examining their in vitro and in vivo binding affinities for the Cxcl12 promoter in a pancreatic beta cell line by the electrophoretic mobility shift assay and chromatin immunoprecipitation.
1605	23555743	The regulatory activities of PARP-1 and YY1 were assessed in transfection experiments using a reporter vector with a Cxcl12 promoter sequence driving luciferase gene expression.
1606	23555743	Experimental evidence for PARP-1 and YY1 revealed their trans-acting potential, wherein PARP-1 displayed an inhibitory, and YY1 a strong activating effect on Cxcl12 transcription.
1607	23555743	PARP-1 binding to the Cxcl12 promoter during basal and in STZ-compromised conditions led us to conclude that PARP-1 regulates constitutive Cxcl12 expression.
1608	23555743	During the early stage of oxidative stress, YY1 exhibited less affinity toward the Cxcl12 promoter while PARP-1 displayed strong binding.
1609	23555743	In the later stages of oxidative stress and intensive pancreatic beta cell injury, YY1 was highly expressed and firmly bound to Cxcl12 promoter in contrast to PARP-1.
1610	23555743	The observed ability of PARP-1 to downregulate, and of YY1 to upregulate Cxcl12 promoter activity anticipates corresponding effects in the natural context where the functional interplay of these proteins could finely balance Cxcl12 transcription.
1611	23555743	PARP-1 and YY1 are important novel regulators of CXCL12 gene transcription in rat pancreatic beta cells.
1612	23555743	The roles of poly(ADP-ribose) polymerase-1 (PARP-1) and transcription factor Yin Yang 1 (YY1) in Cxcl12 transcription were studied by examining their in vitro and in vivo binding affinities for the Cxcl12 promoter in a pancreatic beta cell line by the electrophoretic mobility shift assay and chromatin immunoprecipitation.
1613	23555743	The regulatory activities of PARP-1 and YY1 were assessed in transfection experiments using a reporter vector with a Cxcl12 promoter sequence driving luciferase gene expression.
1614	23555743	Experimental evidence for PARP-1 and YY1 revealed their trans-acting potential, wherein PARP-1 displayed an inhibitory, and YY1 a strong activating effect on Cxcl12 transcription.
1615	23555743	PARP-1 binding to the Cxcl12 promoter during basal and in STZ-compromised conditions led us to conclude that PARP-1 regulates constitutive Cxcl12 expression.
1616	23555743	During the early stage of oxidative stress, YY1 exhibited less affinity toward the Cxcl12 promoter while PARP-1 displayed strong binding.
1617	23555743	In the later stages of oxidative stress and intensive pancreatic beta cell injury, YY1 was highly expressed and firmly bound to Cxcl12 promoter in contrast to PARP-1.
1618	23555743	The observed ability of PARP-1 to downregulate, and of YY1 to upregulate Cxcl12 promoter activity anticipates corresponding effects in the natural context where the functional interplay of these proteins could finely balance Cxcl12 transcription.
1619	23555743	PARP-1 and YY1 are important novel regulators of CXCL12 gene transcription in rat pancreatic beta cells.
1620	23555743	The roles of poly(ADP-ribose) polymerase-1 (PARP-1) and transcription factor Yin Yang 1 (YY1) in Cxcl12 transcription were studied by examining their in vitro and in vivo binding affinities for the Cxcl12 promoter in a pancreatic beta cell line by the electrophoretic mobility shift assay and chromatin immunoprecipitation.
1621	23555743	The regulatory activities of PARP-1 and YY1 were assessed in transfection experiments using a reporter vector with a Cxcl12 promoter sequence driving luciferase gene expression.
1622	23555743	Experimental evidence for PARP-1 and YY1 revealed their trans-acting potential, wherein PARP-1 displayed an inhibitory, and YY1 a strong activating effect on Cxcl12 transcription.
1623	23555743	PARP-1 binding to the Cxcl12 promoter during basal and in STZ-compromised conditions led us to conclude that PARP-1 regulates constitutive Cxcl12 expression.
1624	23555743	During the early stage of oxidative stress, YY1 exhibited less affinity toward the Cxcl12 promoter while PARP-1 displayed strong binding.
1625	23555743	In the later stages of oxidative stress and intensive pancreatic beta cell injury, YY1 was highly expressed and firmly bound to Cxcl12 promoter in contrast to PARP-1.
1626	23555743	The observed ability of PARP-1 to downregulate, and of YY1 to upregulate Cxcl12 promoter activity anticipates corresponding effects in the natural context where the functional interplay of these proteins could finely balance Cxcl12 transcription.
1627	23555743	PARP-1 and YY1 are important novel regulators of CXCL12 gene transcription in rat pancreatic beta cells.
1628	23555743	The roles of poly(ADP-ribose) polymerase-1 (PARP-1) and transcription factor Yin Yang 1 (YY1) in Cxcl12 transcription were studied by examining their in vitro and in vivo binding affinities for the Cxcl12 promoter in a pancreatic beta cell line by the electrophoretic mobility shift assay and chromatin immunoprecipitation.
1629	23555743	The regulatory activities of PARP-1 and YY1 were assessed in transfection experiments using a reporter vector with a Cxcl12 promoter sequence driving luciferase gene expression.
1630	23555743	Experimental evidence for PARP-1 and YY1 revealed their trans-acting potential, wherein PARP-1 displayed an inhibitory, and YY1 a strong activating effect on Cxcl12 transcription.
1631	23555743	PARP-1 binding to the Cxcl12 promoter during basal and in STZ-compromised conditions led us to conclude that PARP-1 regulates constitutive Cxcl12 expression.
1632	23555743	During the early stage of oxidative stress, YY1 exhibited less affinity toward the Cxcl12 promoter while PARP-1 displayed strong binding.
1633	23555743	In the later stages of oxidative stress and intensive pancreatic beta cell injury, YY1 was highly expressed and firmly bound to Cxcl12 promoter in contrast to PARP-1.
1634	23555743	The observed ability of PARP-1 to downregulate, and of YY1 to upregulate Cxcl12 promoter activity anticipates corresponding effects in the natural context where the functional interplay of these proteins could finely balance Cxcl12 transcription.
1635	23555743	PARP-1 and YY1 are important novel regulators of CXCL12 gene transcription in rat pancreatic beta cells.
1636	23555743	The roles of poly(ADP-ribose) polymerase-1 (PARP-1) and transcription factor Yin Yang 1 (YY1) in Cxcl12 transcription were studied by examining their in vitro and in vivo binding affinities for the Cxcl12 promoter in a pancreatic beta cell line by the electrophoretic mobility shift assay and chromatin immunoprecipitation.
1637	23555743	The regulatory activities of PARP-1 and YY1 were assessed in transfection experiments using a reporter vector with a Cxcl12 promoter sequence driving luciferase gene expression.
1638	23555743	Experimental evidence for PARP-1 and YY1 revealed their trans-acting potential, wherein PARP-1 displayed an inhibitory, and YY1 a strong activating effect on Cxcl12 transcription.
1639	23555743	PARP-1 binding to the Cxcl12 promoter during basal and in STZ-compromised conditions led us to conclude that PARP-1 regulates constitutive Cxcl12 expression.
1640	23555743	During the early stage of oxidative stress, YY1 exhibited less affinity toward the Cxcl12 promoter while PARP-1 displayed strong binding.
1641	23555743	In the later stages of oxidative stress and intensive pancreatic beta cell injury, YY1 was highly expressed and firmly bound to Cxcl12 promoter in contrast to PARP-1.
1642	23555743	The observed ability of PARP-1 to downregulate, and of YY1 to upregulate Cxcl12 promoter activity anticipates corresponding effects in the natural context where the functional interplay of these proteins could finely balance Cxcl12 transcription.
1643	23616419	Caspase 3 activation and PARP cleavage in lymphocytes from newborn babies of diabetic mothers with unbalanced glycaemic control.
1644	23616419	The aim of this study was to investigate the presence and processing of caspase 3 (Casp3) and poly(ADP-ribose) polymerase 1 (PARP1) in cord blood lymphocytes as markers of apoptosis in relation to glycaemic control during intrauterine life.
1645	23616419	Our results showed a specific positive correlation between the levels of active Casp3 (17-19 kDa) and the inactive form of PARP1 (89 kDa) in lymphocytes isolated from newborn babies of diabetic women with unbalanced glycaemic control, with a direct correlation between the activation of casp3 and the inactivation of PARP1, that makes lymphocytes unresponsive towards lipopolysaccharide stimulation, highlighting an altered functional response.
1646	23616419	Caspase 3 activation and PARP cleavage in lymphocytes from newborn babies of diabetic mothers with unbalanced glycaemic control.
1647	23616419	The aim of this study was to investigate the presence and processing of caspase 3 (Casp3) and poly(ADP-ribose) polymerase 1 (PARP1) in cord blood lymphocytes as markers of apoptosis in relation to glycaemic control during intrauterine life.
1648	23616419	Our results showed a specific positive correlation between the levels of active Casp3 (17-19 kDa) and the inactive form of PARP1 (89 kDa) in lymphocytes isolated from newborn babies of diabetic women with unbalanced glycaemic control, with a direct correlation between the activation of casp3 and the inactivation of PARP1, that makes lymphocytes unresponsive towards lipopolysaccharide stimulation, highlighting an altered functional response.
1649	23876631	The mechanisms implicated in selective damage are not completely understood but many factors have been identified including excitotoxicity, oxidative stress, zinc release, PARP-1 activation and mitochondrial dysfunction.
1650	23954400	Parp1 deficient mice are protected from streptozotocin-induced diabetes but not caerulein-induced pancreatitis, independent of the induction of Reg family genes.
1651	23954400	Poly(ADP-ribose) polymerase (Parp) 1 is a key regulator of cell death, its inhibition prevented streptozotocin-induced diabetes and attenuated caerulein-induced acute pancreatitis.
1652	23954400	Reg family proteins are significantly induced by Parp1 inhibitor, experimental diabetes and/or acute pancreatitis.
1653	23954400	We propose that Reg proteins are involved in the protection of pancreatic cells by Parp1 inhibition.
1654	23954400	Upon streptozotocin administration, Parp1-/- mice displayed much decreased hyperglycemia and preserved serum insulin level.
1655	23954400	The treatment induced similar levels of Reg1, -2, -3α and -3β genes in the pancreas of both wild-type and Parp1-/- mice, suggesting that the upregulation of Reg family genes during streptozotocin-induced diabetes was independent of Parp1 ablation.
1656	23954400	In caerulein-induced pancreatitis, unlike being reported, Parp1 knockout caused no relief on the severity of pancreatitis; the upregulation of pancreatic Reg1, -2, -3α and -3β genes upon caerulein was unaffected by Parp1 deletion.
1657	23954400	Our results reconfirmed the protective effect of Parp1 gene deletion on islet β-cells but questioned its effect on the acinar cells.
1658	23954400	In either case, the significant induction of Reg family genes seemed independent of Parp1-mediated cell death.
1659	23954400	Parp1 deficient mice are protected from streptozotocin-induced diabetes but not caerulein-induced pancreatitis, independent of the induction of Reg family genes.
1660	23954400	Poly(ADP-ribose) polymerase (Parp) 1 is a key regulator of cell death, its inhibition prevented streptozotocin-induced diabetes and attenuated caerulein-induced acute pancreatitis.
1661	23954400	Reg family proteins are significantly induced by Parp1 inhibitor, experimental diabetes and/or acute pancreatitis.
1662	23954400	We propose that Reg proteins are involved in the protection of pancreatic cells by Parp1 inhibition.
1663	23954400	Upon streptozotocin administration, Parp1-/- mice displayed much decreased hyperglycemia and preserved serum insulin level.
1664	23954400	The treatment induced similar levels of Reg1, -2, -3α and -3β genes in the pancreas of both wild-type and Parp1-/- mice, suggesting that the upregulation of Reg family genes during streptozotocin-induced diabetes was independent of Parp1 ablation.
1665	23954400	In caerulein-induced pancreatitis, unlike being reported, Parp1 knockout caused no relief on the severity of pancreatitis; the upregulation of pancreatic Reg1, -2, -3α and -3β genes upon caerulein was unaffected by Parp1 deletion.
1666	23954400	Our results reconfirmed the protective effect of Parp1 gene deletion on islet β-cells but questioned its effect on the acinar cells.
1667	23954400	In either case, the significant induction of Reg family genes seemed independent of Parp1-mediated cell death.
1668	23954400	Parp1 deficient mice are protected from streptozotocin-induced diabetes but not caerulein-induced pancreatitis, independent of the induction of Reg family genes.
1669	23954400	Poly(ADP-ribose) polymerase (Parp) 1 is a key regulator of cell death, its inhibition prevented streptozotocin-induced diabetes and attenuated caerulein-induced acute pancreatitis.
1670	23954400	Reg family proteins are significantly induced by Parp1 inhibitor, experimental diabetes and/or acute pancreatitis.
1671	23954400	We propose that Reg proteins are involved in the protection of pancreatic cells by Parp1 inhibition.
1672	23954400	Upon streptozotocin administration, Parp1-/- mice displayed much decreased hyperglycemia and preserved serum insulin level.
1673	23954400	The treatment induced similar levels of Reg1, -2, -3α and -3β genes in the pancreas of both wild-type and Parp1-/- mice, suggesting that the upregulation of Reg family genes during streptozotocin-induced diabetes was independent of Parp1 ablation.
1674	23954400	In caerulein-induced pancreatitis, unlike being reported, Parp1 knockout caused no relief on the severity of pancreatitis; the upregulation of pancreatic Reg1, -2, -3α and -3β genes upon caerulein was unaffected by Parp1 deletion.
1675	23954400	Our results reconfirmed the protective effect of Parp1 gene deletion on islet β-cells but questioned its effect on the acinar cells.
1676	23954400	In either case, the significant induction of Reg family genes seemed independent of Parp1-mediated cell death.
1677	23954400	Parp1 deficient mice are protected from streptozotocin-induced diabetes but not caerulein-induced pancreatitis, independent of the induction of Reg family genes.
1678	23954400	Poly(ADP-ribose) polymerase (Parp) 1 is a key regulator of cell death, its inhibition prevented streptozotocin-induced diabetes and attenuated caerulein-induced acute pancreatitis.
1679	23954400	Reg family proteins are significantly induced by Parp1 inhibitor, experimental diabetes and/or acute pancreatitis.
1680	23954400	We propose that Reg proteins are involved in the protection of pancreatic cells by Parp1 inhibition.
1681	23954400	Upon streptozotocin administration, Parp1-/- mice displayed much decreased hyperglycemia and preserved serum insulin level.
1682	23954400	The treatment induced similar levels of Reg1, -2, -3α and -3β genes in the pancreas of both wild-type and Parp1-/- mice, suggesting that the upregulation of Reg family genes during streptozotocin-induced diabetes was independent of Parp1 ablation.
1683	23954400	In caerulein-induced pancreatitis, unlike being reported, Parp1 knockout caused no relief on the severity of pancreatitis; the upregulation of pancreatic Reg1, -2, -3α and -3β genes upon caerulein was unaffected by Parp1 deletion.
1684	23954400	Our results reconfirmed the protective effect of Parp1 gene deletion on islet β-cells but questioned its effect on the acinar cells.
1685	23954400	In either case, the significant induction of Reg family genes seemed independent of Parp1-mediated cell death.
1686	23954400	Parp1 deficient mice are protected from streptozotocin-induced diabetes but not caerulein-induced pancreatitis, independent of the induction of Reg family genes.
1687	23954400	Poly(ADP-ribose) polymerase (Parp) 1 is a key regulator of cell death, its inhibition prevented streptozotocin-induced diabetes and attenuated caerulein-induced acute pancreatitis.
1688	23954400	Reg family proteins are significantly induced by Parp1 inhibitor, experimental diabetes and/or acute pancreatitis.
1689	23954400	We propose that Reg proteins are involved in the protection of pancreatic cells by Parp1 inhibition.
1690	23954400	Upon streptozotocin administration, Parp1-/- mice displayed much decreased hyperglycemia and preserved serum insulin level.
1691	23954400	The treatment induced similar levels of Reg1, -2, -3α and -3β genes in the pancreas of both wild-type and Parp1-/- mice, suggesting that the upregulation of Reg family genes during streptozotocin-induced diabetes was independent of Parp1 ablation.
1692	23954400	In caerulein-induced pancreatitis, unlike being reported, Parp1 knockout caused no relief on the severity of pancreatitis; the upregulation of pancreatic Reg1, -2, -3α and -3β genes upon caerulein was unaffected by Parp1 deletion.
1693	23954400	Our results reconfirmed the protective effect of Parp1 gene deletion on islet β-cells but questioned its effect on the acinar cells.
1694	23954400	In either case, the significant induction of Reg family genes seemed independent of Parp1-mediated cell death.
1695	23954400	Parp1 deficient mice are protected from streptozotocin-induced diabetes but not caerulein-induced pancreatitis, independent of the induction of Reg family genes.
1696	23954400	Poly(ADP-ribose) polymerase (Parp) 1 is a key regulator of cell death, its inhibition prevented streptozotocin-induced diabetes and attenuated caerulein-induced acute pancreatitis.
1697	23954400	Reg family proteins are significantly induced by Parp1 inhibitor, experimental diabetes and/or acute pancreatitis.
1698	23954400	We propose that Reg proteins are involved in the protection of pancreatic cells by Parp1 inhibition.
1699	23954400	Upon streptozotocin administration, Parp1-/- mice displayed much decreased hyperglycemia and preserved serum insulin level.
1700	23954400	The treatment induced similar levels of Reg1, -2, -3α and -3β genes in the pancreas of both wild-type and Parp1-/- mice, suggesting that the upregulation of Reg family genes during streptozotocin-induced diabetes was independent of Parp1 ablation.
1701	23954400	In caerulein-induced pancreatitis, unlike being reported, Parp1 knockout caused no relief on the severity of pancreatitis; the upregulation of pancreatic Reg1, -2, -3α and -3β genes upon caerulein was unaffected by Parp1 deletion.
1702	23954400	Our results reconfirmed the protective effect of Parp1 gene deletion on islet β-cells but questioned its effect on the acinar cells.
1703	23954400	In either case, the significant induction of Reg family genes seemed independent of Parp1-mediated cell death.
1704	23954400	Parp1 deficient mice are protected from streptozotocin-induced diabetes but not caerulein-induced pancreatitis, independent of the induction of Reg family genes.
1705	23954400	Poly(ADP-ribose) polymerase (Parp) 1 is a key regulator of cell death, its inhibition prevented streptozotocin-induced diabetes and attenuated caerulein-induced acute pancreatitis.
1706	23954400	Reg family proteins are significantly induced by Parp1 inhibitor, experimental diabetes and/or acute pancreatitis.
1707	23954400	We propose that Reg proteins are involved in the protection of pancreatic cells by Parp1 inhibition.
1708	23954400	Upon streptozotocin administration, Parp1-/- mice displayed much decreased hyperglycemia and preserved serum insulin level.
1709	23954400	The treatment induced similar levels of Reg1, -2, -3α and -3β genes in the pancreas of both wild-type and Parp1-/- mice, suggesting that the upregulation of Reg family genes during streptozotocin-induced diabetes was independent of Parp1 ablation.
1710	23954400	In caerulein-induced pancreatitis, unlike being reported, Parp1 knockout caused no relief on the severity of pancreatitis; the upregulation of pancreatic Reg1, -2, -3α and -3β genes upon caerulein was unaffected by Parp1 deletion.
1711	23954400	Our results reconfirmed the protective effect of Parp1 gene deletion on islet β-cells but questioned its effect on the acinar cells.
1712	23954400	In either case, the significant induction of Reg family genes seemed independent of Parp1-mediated cell death.
1713	23954400	Parp1 deficient mice are protected from streptozotocin-induced diabetes but not caerulein-induced pancreatitis, independent of the induction of Reg family genes.
1714	23954400	Poly(ADP-ribose) polymerase (Parp) 1 is a key regulator of cell death, its inhibition prevented streptozotocin-induced diabetes and attenuated caerulein-induced acute pancreatitis.
1715	23954400	Reg family proteins are significantly induced by Parp1 inhibitor, experimental diabetes and/or acute pancreatitis.
1716	23954400	We propose that Reg proteins are involved in the protection of pancreatic cells by Parp1 inhibition.
1717	23954400	Upon streptozotocin administration, Parp1-/- mice displayed much decreased hyperglycemia and preserved serum insulin level.
1718	23954400	The treatment induced similar levels of Reg1, -2, -3α and -3β genes in the pancreas of both wild-type and Parp1-/- mice, suggesting that the upregulation of Reg family genes during streptozotocin-induced diabetes was independent of Parp1 ablation.
1719	23954400	In caerulein-induced pancreatitis, unlike being reported, Parp1 knockout caused no relief on the severity of pancreatitis; the upregulation of pancreatic Reg1, -2, -3α and -3β genes upon caerulein was unaffected by Parp1 deletion.
1720	23954400	Our results reconfirmed the protective effect of Parp1 gene deletion on islet β-cells but questioned its effect on the acinar cells.
1721	23954400	In either case, the significant induction of Reg family genes seemed independent of Parp1-mediated cell death.
1722	23954400	Parp1 deficient mice are protected from streptozotocin-induced diabetes but not caerulein-induced pancreatitis, independent of the induction of Reg family genes.
1723	23954400	Poly(ADP-ribose) polymerase (Parp) 1 is a key regulator of cell death, its inhibition prevented streptozotocin-induced diabetes and attenuated caerulein-induced acute pancreatitis.
1724	23954400	Reg family proteins are significantly induced by Parp1 inhibitor, experimental diabetes and/or acute pancreatitis.
1725	23954400	We propose that Reg proteins are involved in the protection of pancreatic cells by Parp1 inhibition.
1726	23954400	Upon streptozotocin administration, Parp1-/- mice displayed much decreased hyperglycemia and preserved serum insulin level.
1727	23954400	The treatment induced similar levels of Reg1, -2, -3α and -3β genes in the pancreas of both wild-type and Parp1-/- mice, suggesting that the upregulation of Reg family genes during streptozotocin-induced diabetes was independent of Parp1 ablation.
1728	23954400	In caerulein-induced pancreatitis, unlike being reported, Parp1 knockout caused no relief on the severity of pancreatitis; the upregulation of pancreatic Reg1, -2, -3α and -3β genes upon caerulein was unaffected by Parp1 deletion.
1729	23954400	Our results reconfirmed the protective effect of Parp1 gene deletion on islet β-cells but questioned its effect on the acinar cells.
1730	23954400	In either case, the significant induction of Reg family genes seemed independent of Parp1-mediated cell death.