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Gene Information
Gene symbol: CASP8
Gene name: caspase 8, apoptosis-related cysteine peptidase
HGNC ID: 1509
Synonyms: MCH5, MACH, FLICE, Casp-8
Related Genes
Related Sentences
| # | PMID | Sentence |
| 1 | 9218757 | Protection of NIT-1 pancreatic beta-cells from immune attack by inhibition of NF-kappaB. |
| 2 | 9218757 | We have recently observed that inhibition of NF-kappaB in NIT-1 insulinoma cells protects them from tumour necrosis factor (TNF)-induced cell death in vitro, possibly because expression of interleukin-1 (IL-1)beta-converting enzyme (ICE), a member of the cysteine protease pathway of cell death, is decreased. |
| 3 | 9218757 | In the current study we have examined the effect of the same inhibitor of NF-kappaB on class I major histocompatibility complex (MHC) protein expression in NIT-1 cells and shown that inhibition of NF-kappaB activation decreased basal and TNF-induced class I MHC levels. |
| 4 | 9218757 | Although inducible nitric oxide synthase (iNOS) may also be inhibited by inhibition of NF-kappaB, this could not be demonstrated in NIT-1/delta sp cells because wild-type NIT-1 cells express very little iNOS. |
| 5 | 9218757 | When NIT-1/delta sp12 cells, expressing high levels of the NF-kappaB inhibitor, are transplanted into immunodeficient NOD/scid mice, tumorigenesis and death by hypoglycemia proceed similarly to untransfected NIT-1 cells. |
| 6 | 9218757 | In conclusion, inhibition of NF-kappaB is likely to suppress several different pathways of immune-mediated cell death in beta-cells and protects NIT-1 cells from immune attack by diabetogenic T cells in vivo. |
| 7 | 10690898 | Interferon-gamma induces interleukin-1 converting enzyme expression in pancreatic islets by an interferon regulatory factor-1-dependent mechanism. |
| 8 | 10690898 | The cysteine protease interleukin (IL)-1 converting enzyme (ICE) is a key proapoptotic caspase. |
| 9 | 10690898 | ICE messenger RNA (mRNA) expression was highly up-regulated after 6-, 24-, and 72-h exposure of human islets to interferon (IFN)gamma, tumor necrosis factor (TNF)alpha + IFNgamma or IL-1beta + TNFalpha + IFNgamma, paralleled by increased iNOS (the inducible form of NO synthase) expression and NO production after exposure to the combined cytokines but not to IFNgamma or TNFalpha + IFNgamma. |
| 10 | 10690898 | Cytokine-induced NO-independent ICE transcription was confirmed using iNOS inhibitors. |
| 11 | 10690898 | Exposure of rat and mouse islets, or rat insulinoma cells, for 24 h to IFNgamma alone or in combination with the two other cytokines also resulted in a highly significant ICE mRNA expression. |
| 12 | 10690898 | ICE transcription was not inducible in islets from IFN regulatory factor-1 knock-out mice, suggesting a key-role of this transcription-factor in cytokine-mediated ICE expression in pancreatic islets. |
| 13 | 10690898 | In conclusion, cytokines and IFNgamma in particular increase ICE mRNA expression in pancreatic islet cells and beta-cell lines, independently of NO synthesis, suggesting that ICE up-regulation may be involved in cytokine-induced NO-independent apoptosis of human islets. |
| 14 | 10940305 | The glucagon-like peptide-2 receptor mediates direct inhibition of cellular apoptosis via a cAMP-dependent protein kinase-independent pathway. |
| 15 | 10940305 | Because GLP-2 decreases mortality and reduces intestinal apoptosis in rodents after experimental injury, we examined whether GLP-2R signaling directly modifies the cellular response to external injury. |
| 16 | 10940305 | We show here that activation of GLP-2R signaling inhibits cycloheximide-induced apoptosis in baby hamster kidney fibroblasts expressing a transfected GLP-2 receptor. |
| 17 | 10940305 | GLP-2 reduced DNA fragmentation and improved cell survival, in association with reduced activation of caspase-3 and decreased poly(ADP-ribose) polymerase cleavage and reduced caspase-8 and caspase-9-like activities. |
| 18 | 10940305 | Both GLP-2 and forskolin reduced mitochondrial cytochrome c release and decreased the cycloheximide-induced cleavage of caspase-3 in the presence or absence of the PKA inhibitor H-89. |
| 19 | 10940305 | These findings provide evidence that signaling through G protein-coupled receptors of the glucagon superfamily is directly linked to regulation of apoptosis and suggest the existence of a cAMP-dependent protein kinase-, phosphatidylinositol 3-kinase-, and mitogen-activated protein kinase-independent pathway coupling GLP-2R signaling to caspase inhibition and cell survival. |
| 20 | 11016460 | NOD Idd5 locus controls insulitis and diabetes and overlaps the orthologous CTLA4/IDDM12 and NRAMP1 loci in humans. |
| 21 | 11016460 | This locus was designated Idd5 and encompassed candidate genes including Il1r1, Il1r2, Stat1, Stat4, Nramp1, and Bcl2. |
| 22 | 11016460 | Idd5.1 is in the proximal 1.5-cM portion of the interval and contains the candidates Casp8, Cflar (FLIP), Cd28, and Cd152 (CTLA4). |
| 23 | 11016460 | Idd5.2 is in the distal 5.1-cM portion of the 9.4-cM interval and contains the candidates Nramp1, which has a functional polymorphism between NOD and B10, and Cmkar2 (CXCR2, interleukin [IL]-8 receptor alpha). |
| 24 | 11016460 | Candidate genes eliminated by this analysis include Il1r1, Ilr2, Zap70, Orch5, Stat1, Stat4, Bcl2, Cmkar4 (CXCR4), and Il10. |
| 25 | 11017071 | This putative diabetes-susceptibility gene encodes a ubiquitously expressed member of the calpain-like cysteine protease family, calpain-10 (CAPN10). |
| 26 | 11165713 | TCR stimulation protects CD8+ T cells from CD95 mediated apoptosis. |
| 27 | 11165713 | Activation of T cells through the T-cell receptor (TCR) induces the expression of Fas Ligand (CD95L). |
| 28 | 11165713 | In turn, CD95L binds to the Fas receptor (CD95) and rapidly induces apoptosis in cycling cells. |
| 29 | 11165713 | Here we show that a short (2 to 3 h) activation of T cells through the TCR simultaneously induces an increase in CD95L mRNA and a dramatic decrease in caspase-8 mRNA levels and proteolytic activity in human CD8(+) T cells. |
| 30 | 11221847 | Induction and intracellular regulation of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) mediated apotosis in human malignant glioma cells. |
| 31 | 11221847 | Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) preferentially triggers apoptosis in tumor cells versus normal cells, thus providing a therapeutic potential. |
| 32 | 11221847 | TRAIL-induced cell death was characterized by activation of caspase-8 and -3, poly(ADP-ribose) polymerase cleavage, and DNA fragmentation. |
| 33 | 11221847 | Decoy receptor (DcR1 and DcR2) expression was limited in the glioma cell lines and did not correlate with TRAIL sensitivity. |
| 34 | 11221847 | Both sensitive and resistant cell lines expressed TRAIL death receptor (DR5), adapter protein Fas-associated death domain (FADD), and caspase-8; but resistant cell lines expressed 2-fold higher levels of the apoptosis inhibitor phosphoprotein enriched in diabetes/phosphoprotein enriched in astrocytes-15 kDa (PED/PEA-15). |
| 35 | 11221847 | In contrast, cellular FADD-like IL-1beta-converting enzyme-like inhibitory protein (cFLIP) expression was similar in sensitive and resistant cells. |
| 36 | 11221847 | Inhibition of protein kinase C (PKC) activity restored TRAIL sensitivity in resistant cells, suggesting that PED/ PEA-15 function might be dependent on PKC-mediated phosphorylation. |
| 37 | 11221847 | This caspase-8-induced apoptotic cascade is regulated by intracellular PED/PEA-15, but not by cFLIP or decoy receptors. |
| 38 | 11221847 | Induction and intracellular regulation of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) mediated apotosis in human malignant glioma cells. |
| 39 | 11221847 | Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) preferentially triggers apoptosis in tumor cells versus normal cells, thus providing a therapeutic potential. |
| 40 | 11221847 | TRAIL-induced cell death was characterized by activation of caspase-8 and -3, poly(ADP-ribose) polymerase cleavage, and DNA fragmentation. |
| 41 | 11221847 | Decoy receptor (DcR1 and DcR2) expression was limited in the glioma cell lines and did not correlate with TRAIL sensitivity. |
| 42 | 11221847 | Both sensitive and resistant cell lines expressed TRAIL death receptor (DR5), adapter protein Fas-associated death domain (FADD), and caspase-8; but resistant cell lines expressed 2-fold higher levels of the apoptosis inhibitor phosphoprotein enriched in diabetes/phosphoprotein enriched in astrocytes-15 kDa (PED/PEA-15). |
| 43 | 11221847 | In contrast, cellular FADD-like IL-1beta-converting enzyme-like inhibitory protein (cFLIP) expression was similar in sensitive and resistant cells. |
| 44 | 11221847 | Inhibition of protein kinase C (PKC) activity restored TRAIL sensitivity in resistant cells, suggesting that PED/ PEA-15 function might be dependent on PKC-mediated phosphorylation. |
| 45 | 11221847 | This caspase-8-induced apoptotic cascade is regulated by intracellular PED/PEA-15, but not by cFLIP or decoy receptors. |
| 46 | 11221847 | Induction and intracellular regulation of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) mediated apotosis in human malignant glioma cells. |
| 47 | 11221847 | Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) preferentially triggers apoptosis in tumor cells versus normal cells, thus providing a therapeutic potential. |
| 48 | 11221847 | TRAIL-induced cell death was characterized by activation of caspase-8 and -3, poly(ADP-ribose) polymerase cleavage, and DNA fragmentation. |
| 49 | 11221847 | Decoy receptor (DcR1 and DcR2) expression was limited in the glioma cell lines and did not correlate with TRAIL sensitivity. |
| 50 | 11221847 | Both sensitive and resistant cell lines expressed TRAIL death receptor (DR5), adapter protein Fas-associated death domain (FADD), and caspase-8; but resistant cell lines expressed 2-fold higher levels of the apoptosis inhibitor phosphoprotein enriched in diabetes/phosphoprotein enriched in astrocytes-15 kDa (PED/PEA-15). |
| 51 | 11221847 | In contrast, cellular FADD-like IL-1beta-converting enzyme-like inhibitory protein (cFLIP) expression was similar in sensitive and resistant cells. |
| 52 | 11221847 | Inhibition of protein kinase C (PKC) activity restored TRAIL sensitivity in resistant cells, suggesting that PED/ PEA-15 function might be dependent on PKC-mediated phosphorylation. |
| 53 | 11221847 | This caspase-8-induced apoptotic cascade is regulated by intracellular PED/PEA-15, but not by cFLIP or decoy receptors. |
| 54 | 11473025 | In autoimmune type 1 diabetes, Fas-to-Fas-ligand (FasL) interaction may represent one of the essential pro-apoptotic pathways leading to a loss of pancreatic beta-cells. |
| 55 | 11473025 | Human islets normally express FasL but not the Fas receptor. |
| 56 | 11473025 | In vitro exposure of islets from nondiabetic organ donors to high glucose levels induced Fas expression, caspase-8 and -3 activation, and beta-cell apoptosis. |
| 57 | 11473025 | The effect of glucose was blocked by an antagonistic anti-Fas antibody, indicating that glucose-induced apoptosis is due to interaction between the constitutively expressed FasL and the upregulated Fas. |
| 58 | 11473025 | Upregulation of the Fas receptor by elevated glucose levels may contribute to beta-cell destruction by the constitutively expressed FasL independent of an autoimmune reaction, thus providing a link between type 1 and type 2 diabetes. |
| 59 | 11481585 | Variation in CAPN10, the gene encoding the ubiquitously expressed cysteine protease calpain-10, has been associated with type 2 diabetes in Mexican Americans and in two northern-European populations, from Finland and Germany. |
| 60 | 11668341 | The defect was apparent in vivo as well as in vitro, was independent of IAbetag7 expression and affected both Fas-dependent and Fas-independent pathways of apoptosis; for Fas-dependent apoptosis, the defective tolerance of NOD thymocytes correlated with the strong T cell receptor-mediated up-regulation of caspase 8-homologous FLICE (Fas-associated death-domain-like interleukin 1beta-converting enzyme)-inhibitory protein. |
| 61 | 11723074 | This interval now excludes the Casp8 and Cflar (Flip) candidate genes. |
| 62 | 11723074 | It still retains Cd28 and Ctla4 and also includes Icos (inducible costimulator). |
| 63 | 11723074 | The previously reported differential expression of Ctla4, which is induced at a lower level in NOD than in B6-activated T-cells, was found independent of Idd5.1 itself because Ctla4 expression was induced at a low level in T-cells from Idd5.1-congenic mice. |
| 64 | 11932299 | Recent evidence suggests that variation in the gene encoding the cysteine protease calpain-10 influences susceptibility to type 2 diabetes. |
| 65 | 11976344 | Tumor necrosis factor-related apoptosis-inducing ligand-induced death-inducing signaling complex and its modulation by c-FLIP and PED/PEA-15 in glioma cells. |
| 66 | 11976344 | Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) can trigger apoptosis in some tumor cells but not other tumor cells. |
| 67 | 11976344 | Caspase-8 and caspase-10 were recruited to the DISC, where they were proteolytically activated to initiate apoptosis in TRAIL-sensitive glioma cells. |
| 68 | 11976344 | Caspase-8 and caspase-10 were also recruited to the DISC in TRAIL-resistant cells, but their further activation was inhibited by two antiapoptotic proteins termed cellular Fas-associated death domain-like interleukin-1beta-converting enzyme-inhibitory protein (c-FLIP) and phosphoprotein enriched in diabetes/phosphoprotein enriched in astrocytes-15kDa (PED/PEA-15). |
| 69 | 11976344 | Of the three isoforms of PED/PEA-15 proteins, only the doubly phosphorylated form was expressed and recruited to the DISC in TRAIL-resistant cells, indicating that the phosphorylation status of PED/PEA-15 determines its recruitment in the cells. |
| 70 | 11976344 | Tumor necrosis factor-related apoptosis-inducing ligand-induced death-inducing signaling complex and its modulation by c-FLIP and PED/PEA-15 in glioma cells. |
| 71 | 11976344 | Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) can trigger apoptosis in some tumor cells but not other tumor cells. |
| 72 | 11976344 | Caspase-8 and caspase-10 were recruited to the DISC, where they were proteolytically activated to initiate apoptosis in TRAIL-sensitive glioma cells. |
| 73 | 11976344 | Caspase-8 and caspase-10 were also recruited to the DISC in TRAIL-resistant cells, but their further activation was inhibited by two antiapoptotic proteins termed cellular Fas-associated death domain-like interleukin-1beta-converting enzyme-inhibitory protein (c-FLIP) and phosphoprotein enriched in diabetes/phosphoprotein enriched in astrocytes-15kDa (PED/PEA-15). |
| 74 | 11976344 | Of the three isoforms of PED/PEA-15 proteins, only the doubly phosphorylated form was expressed and recruited to the DISC in TRAIL-resistant cells, indicating that the phosphorylation status of PED/PEA-15 determines its recruitment in the cells. |
| 75 | 12031968 | cFLIP protein prevents tumor necrosis factor-alpha-mediated induction of caspase-8-dependent apoptosis in insulin-secreting betaTc-Tet cells. |
| 76 | 12031968 | The exact role played by interferon-gamma, tumor necrosis factor (TNF)-alpha, and interleukin-1beta in this pathogenic process is still only partially understood. |
| 77 | 12031968 | We previously reported that it was susceptible to apoptosis induced by TNF-alpha, in combination with interleukin-1beta and interferon-gamma. |
| 78 | 12031968 | We show that in betaTc-Tet cells, overexpression of cFLIP, the cellular FLICE (FADD-like IL-1beta-converting enzyme)-inhibitory protein, completely abolished cytokine-dependent activation of caspase-8 and protected the cells against apoptosis. |
| 79 | 12031968 | Furthermore, cFLIP overexpression increased the basal and interleukin-1beta-mediated transcriptional activity of nuclear factor (NF)-kappaB, whereas it did not change cytokine-induced inducible nitric oxide synthase gene transcription and nitric oxide secretion. |
| 80 | 12031968 | The presence of cFLIP prevented the weak TNF-alpha-induced reduction in cellular insulin content and secretion; however, it did not prevent the decrease in glucose-stimulated insulin secretion induced by the combined cytokines, in agreement with our previous data demonstrating that interferon-gamma alone could induce these beta-cell dysfunctions. |
| 81 | 12031968 | Together, our data demonstrate that overexpression of cFLIP protects mouse beta-cells against TNF-alpha-induced caspase-8 activation and apoptosis and is correlated with enhanced NF-kappaB transcriptional activity, suggesting that cFLIP may have an impact on the outcome of death receptor-triggered responses by directing the intracellular signals from beta-cell death to beta-cell survival. |
| 82 | 12031968 | cFLIP protein prevents tumor necrosis factor-alpha-mediated induction of caspase-8-dependent apoptosis in insulin-secreting betaTc-Tet cells. |
| 83 | 12031968 | The exact role played by interferon-gamma, tumor necrosis factor (TNF)-alpha, and interleukin-1beta in this pathogenic process is still only partially understood. |
| 84 | 12031968 | We previously reported that it was susceptible to apoptosis induced by TNF-alpha, in combination with interleukin-1beta and interferon-gamma. |
| 85 | 12031968 | We show that in betaTc-Tet cells, overexpression of cFLIP, the cellular FLICE (FADD-like IL-1beta-converting enzyme)-inhibitory protein, completely abolished cytokine-dependent activation of caspase-8 and protected the cells against apoptosis. |
| 86 | 12031968 | Furthermore, cFLIP overexpression increased the basal and interleukin-1beta-mediated transcriptional activity of nuclear factor (NF)-kappaB, whereas it did not change cytokine-induced inducible nitric oxide synthase gene transcription and nitric oxide secretion. |
| 87 | 12031968 | The presence of cFLIP prevented the weak TNF-alpha-induced reduction in cellular insulin content and secretion; however, it did not prevent the decrease in glucose-stimulated insulin secretion induced by the combined cytokines, in agreement with our previous data demonstrating that interferon-gamma alone could induce these beta-cell dysfunctions. |
| 88 | 12031968 | Together, our data demonstrate that overexpression of cFLIP protects mouse beta-cells against TNF-alpha-induced caspase-8 activation and apoptosis and is correlated with enhanced NF-kappaB transcriptional activity, suggesting that cFLIP may have an impact on the outcome of death receptor-triggered responses by directing the intracellular signals from beta-cell death to beta-cell survival. |
| 89 | 12031968 | cFLIP protein prevents tumor necrosis factor-alpha-mediated induction of caspase-8-dependent apoptosis in insulin-secreting betaTc-Tet cells. |
| 90 | 12031968 | The exact role played by interferon-gamma, tumor necrosis factor (TNF)-alpha, and interleukin-1beta in this pathogenic process is still only partially understood. |
| 91 | 12031968 | We previously reported that it was susceptible to apoptosis induced by TNF-alpha, in combination with interleukin-1beta and interferon-gamma. |
| 92 | 12031968 | We show that in betaTc-Tet cells, overexpression of cFLIP, the cellular FLICE (FADD-like IL-1beta-converting enzyme)-inhibitory protein, completely abolished cytokine-dependent activation of caspase-8 and protected the cells against apoptosis. |
| 93 | 12031968 | Furthermore, cFLIP overexpression increased the basal and interleukin-1beta-mediated transcriptional activity of nuclear factor (NF)-kappaB, whereas it did not change cytokine-induced inducible nitric oxide synthase gene transcription and nitric oxide secretion. |
| 94 | 12031968 | The presence of cFLIP prevented the weak TNF-alpha-induced reduction in cellular insulin content and secretion; however, it did not prevent the decrease in glucose-stimulated insulin secretion induced by the combined cytokines, in agreement with our previous data demonstrating that interferon-gamma alone could induce these beta-cell dysfunctions. |
| 95 | 12031968 | Together, our data demonstrate that overexpression of cFLIP protects mouse beta-cells against TNF-alpha-induced caspase-8 activation and apoptosis and is correlated with enhanced NF-kappaB transcriptional activity, suggesting that cFLIP may have an impact on the outcome of death receptor-triggered responses by directing the intracellular signals from beta-cell death to beta-cell survival. |
| 96 | 12060768 | Recently, it has been shown that the caspase-8 inhibitor FLIP may divert Fas-mediated death signals into those for cell proliferation in lymphatic cells. |
| 97 | 12623123 | Tumor necrosis factor alpha-induced apoptosis in astrocytes is prevented by the activation of P2Y6, but not P2Y4 nucleotide receptors. |
| 98 | 12623123 | The physiological role of the uracil nucleotide-preferring P2Y(6) and P2Y(4) receptors is still unclear, although they are widely distributed in various tissues. |
| 99 | 12623123 | In an effort to identify their biological functions, we found that activation by UDP of the rat P2Y(6) receptor expressed in 1321N1 human astrocytes significantly reduced cell death induced by tumor necrosis factor alpha (TNF alpha). |
| 100 | 12623123 | Activation of the human P2Y(4) receptor expressed in 1321N1 cells by UTP did not elicit this protective effect, although both receptors were coupled to phospholipase C. |
| 101 | 12623123 | The activation of P2Y(6) receptors prevented the activation of both caspase-3 and caspase-8 resulting from TNF alpha exposure. |
| 102 | 12623123 | Therefore, it is suggested that P2Y(6) receptors interact rapidly with the TNF alpha-related intracellular signals to prevent apoptotic cell death. |
| 103 | 12639759 | Glucose-induced apoptosis was partially but significantly prevented by SNK-860, an inhibitor of calcium-dependent cysteine protease, calpain, or GSH supplementation, and completely normalized by a caspase-3 inhibitor. |
| 104 | 12639759 | These observations suggest that glucose-induced apoptosis in retinal pericytes, as one of the pathogenic factors of diabetic retinopathy, would be mediated through an aldose reductase-sensitive pathway including calcium-calpain cascade and increased oxidative stress, and that caspase-3 would be located furthest downstream of these apoptotic signals. |
| 105 | 12706864 | Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been shown to exert potent cytotoxic activity against many tumor cells but not normal cells. |
| 106 | 12706864 | We found that most TRAIL-resistant and -partial resistant clones expressed low levels of DR5, whereas most TRAIL-sensitive clones expressed high levels of Death Receptor (DR5). |
| 107 | 12706864 | However, there were clones with a range of different TRAIL-sensitivities that had similar levels of DR5 expression. |
| 108 | 12706864 | The expression levels of DR4 and the decoy receptors, DcR1 and DcR2, did not correlate with TRAIL sensitivities. |
| 109 | 12706864 | We also compared the subgroups in terms of the expression of Fas-associated death domain protein (FADD), the levels of activation of Receptor Interacting Protein (RIP) and caspases, and cleavage of Poly (ADP-Ribose)Polymerase (PARP). |
| 110 | 12706864 | After treatment with TRAIL, both TRAIL-sensitive and partial resistant clones showed high levels of activation of caspase-3, caspase-8, RIP and PARP. |
| 111 | 12706864 | Relative basal level and induced level of Phosphoprotein over Expressed in Diabetes/Phosphoprotein Enriched in Astrocytes (PED/PEA-15) after TRAIL treatment were compared in the clones. |
| 112 | 12706864 | TRAIL did not change the PED/PEA-15 level in the clones. |
| 113 | 12706864 | In addition, transduction and expression of the dominant negative form of the I-kBalpha gene did not change TRAIL-sensitivities. |
| 114 | 12706864 | Our results showed that the expression levels of DR5, the activation levels of caspase-8, -3 and RIP were critical factors in determining TRAIL-sensitivities in Jurkat cells. |
| 115 | 12706864 | Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been shown to exert potent cytotoxic activity against many tumor cells but not normal cells. |
| 116 | 12706864 | We found that most TRAIL-resistant and -partial resistant clones expressed low levels of DR5, whereas most TRAIL-sensitive clones expressed high levels of Death Receptor (DR5). |
| 117 | 12706864 | However, there were clones with a range of different TRAIL-sensitivities that had similar levels of DR5 expression. |
| 118 | 12706864 | The expression levels of DR4 and the decoy receptors, DcR1 and DcR2, did not correlate with TRAIL sensitivities. |
| 119 | 12706864 | We also compared the subgroups in terms of the expression of Fas-associated death domain protein (FADD), the levels of activation of Receptor Interacting Protein (RIP) and caspases, and cleavage of Poly (ADP-Ribose)Polymerase (PARP). |
| 120 | 12706864 | After treatment with TRAIL, both TRAIL-sensitive and partial resistant clones showed high levels of activation of caspase-3, caspase-8, RIP and PARP. |
| 121 | 12706864 | Relative basal level and induced level of Phosphoprotein over Expressed in Diabetes/Phosphoprotein Enriched in Astrocytes (PED/PEA-15) after TRAIL treatment were compared in the clones. |
| 122 | 12706864 | TRAIL did not change the PED/PEA-15 level in the clones. |
| 123 | 12706864 | In addition, transduction and expression of the dominant negative form of the I-kBalpha gene did not change TRAIL-sensitivities. |
| 124 | 12706864 | Our results showed that the expression levels of DR5, the activation levels of caspase-8, -3 and RIP were critical factors in determining TRAIL-sensitivities in Jurkat cells. |
| 125 | 12753807 | Moreover, both CD4(+)and CD8(+)subsets were affected. |
| 126 | 12753807 | Gene expression analysis using real-time RT-PCR additionally revealed low expression of Fas and FasL, the death receptor system activating caspase 8 and contributing to AICD. |
| 127 | 12759879 | Genetic variation in the gene for a cytosolic cysteine protease, calpain-10, increases the susceptibility to type 2 diabetes apparently by altering levels of gene expression. |
| 128 | 12759879 | Exposure of islets to inhibitors of other proteases, ie, cathepsin B and proteasome, did not affect insulin secretion. |
| 129 | 12885274 | Cellular FLIP (c-FLIP), also known as FLICE-inhibitory protein, has been identified as an inhibitor of apoptosis triggered by engagement of death receptors (DRs) such as Fas or TRAIL (TNF-related apoptosis-inducing ligand). cFLIP is recruited to DR signalling complexes, where it prevents caspase activation. |
| 130 | 14532296 | Furthermore, we showed that specific jnk1 antisense oligonucleotides, which suppress phospho-JNK1 expression, effectively decreased human amylin-induced activation of c-Jun. |
| 131 | 14532296 | Studies of the interplay between the caspase cascade and the JNK pathway showed that both apoptosis and caspase-3 activation were suppressed by treatment with a JNK inhibitor and by transfection of antisense jnk1 oligonucleotides or antisense-c-jun, whereas a selective inhibitor of caspases-1 and -3 prevented apoptosis but not c-Jun activation. |
| 132 | 14532296 | However, selective JNK inhibition had no effect on caspase-8 activation, and selective caspase-8 inhibition only partially suppressed apoptosis and c-Jun activation, indicating that caspase-8 may partially act upstream of the JNK pathway. |
| 133 | 14532296 | Fibrillogenic amylin can evoke a JNK1-mediated apoptotic pathway, which is partially dependent and partially independent of caspase-8, and in which caspase-3 acts as a common downstream effector. |
| 134 | 14532296 | Furthermore, we showed that specific jnk1 antisense oligonucleotides, which suppress phospho-JNK1 expression, effectively decreased human amylin-induced activation of c-Jun. |
| 135 | 14532296 | Studies of the interplay between the caspase cascade and the JNK pathway showed that both apoptosis and caspase-3 activation were suppressed by treatment with a JNK inhibitor and by transfection of antisense jnk1 oligonucleotides or antisense-c-jun, whereas a selective inhibitor of caspases-1 and -3 prevented apoptosis but not c-Jun activation. |
| 136 | 14532296 | However, selective JNK inhibition had no effect on caspase-8 activation, and selective caspase-8 inhibition only partially suppressed apoptosis and c-Jun activation, indicating that caspase-8 may partially act upstream of the JNK pathway. |
| 137 | 14532296 | Fibrillogenic amylin can evoke a JNK1-mediated apoptotic pathway, which is partially dependent and partially independent of caspase-8, and in which caspase-3 acts as a common downstream effector. |
| 138 | 14679087 | Caspase 7 is a positional candidate gene for IDDM 17 in a Bedouin Arab family. |
| 139 | 14679087 | Caspase 7 (CASP7), an apoptosis-related cysteine protease, is one of the few known genes in this region. |
| 140 | 15163118 | After Fas triggering, the generation of the active sub-units of caspase-8 is significantly reduced in T1DM T-cells restimulated via TCR/CD3 and/or CD28. |
| 141 | 15246841 | Caspase-3 activation was evident in the nuclear fraction of the cortex of diabetic rats after 3 days recovery and it was preceded by activation of caspase-9, but not activation of caspase-8. |
| 142 | 15246841 | These results suggest that a brief period of global ischemia in diabetic animals activates a neuronal cell death pathway involving cytochrome c release, caspase-9 activation, and caspase-3 cleavage, all of which are most likely initiated by early mitochondria damage. |
| 143 | 15277383 | Caspase-8 activity was reduced in cells cultured on matrix, whereas focal adhesion kinase (FAK), protein kinase B (PKB, or Akt), and extracellular signal-regulated kinase (ERK) phosphorylation was augmented. |
| 144 | 15277383 | Treatment (4 h) with an anti-beta1 integrin antibody, with the ERK pathway inhibitor PD98059, and/or with the phosphatidylinositol 3-kinase inhibitor LY294002 augmented cell death on 804G matrix but not on pLL. |
| 145 | 15362499 | Positional cloning studies mapped T2DM susceptibility to CAPN10, the gene encoding the intracellular cysteine protease, calpain 10. |
| 146 | 15362499 | The presence of both calpain 10 and its mRNA have been demonstrated in tissues from several mammalian species whilst calpain 10 appears to be associated with pathways involved in glucose metabolism, insulin secretion and insulin action. |
| 147 | 15590648 | In vivo experiments established that CML-collagen but not unmodified collagen induced fibroblast apoptosis and that apoptosis was dependent upon caspase-3, -8, and -9 activity. |
| 148 | 15590648 | AGE-induced apoptosis was largely dependent on the effector caspase, caspase-3, which was activated through both cytoplasmic (caspase-8-dependent) and mitochondrial (caspase-9) pathways. |
| 149 | 15703453 | Anti-caspase-8 autoantibody response in silicosis patients is associated with HLA-DRB1, DQB1 and DPB1 alleles. |
| 150 | 15860369 | Calpain is a Ca(2+)-regulated cytosolic cysteine protease that exists mainly in two isoforms and mediates crucial cellular functions, including rearrangement of cytoskeletal proteins, transport of the glucose transporter GLUT4, and protein cleavage to activate various receptors and pro-enzymes. |
| 151 | 15862312 | We show here that long transcribed but untranslated CGG-repeat tracts are toxic to human cells and alter the expression of a wide variety of different genes including caspase-8, CYFIP, Neurotensin and UBE3A. |
| 152 | 15976052 | Caspase 8, p53, and nuclear factor kappaB were more highly activated in diabetic rat pituitaries, with caspase 8 colocalization in lactotrophs being increased. |
| 153 | 16046222 | The cysteine protease inhibitor cystatin-C may be involved in this phenomenon. |
| 154 | 16046222 | Cystatin-C was positively correlated with body mass index (BMI), low-density lipoprotein (LDL)-cholesterol, triglycerides and several inflammatory markers such as fibrinogen (r = 0.18), C-reactive protein (CRP) (r = 0.24), interleukin-6 (= 0.20), tumor necrosis factor-alpha (TNFalpha) (r = 0.27) and two TNFalpha receptors: TNFR1A (r = 0.43) and TNFR1B (r = 0.41); and negatively with high-density lipoprotein (HDL)-cholesterol (r = -0.25). |
| 155 | 16046222 | Cystatin-C is not a more predictive risk marker of CHD than CRP or interleukin-6, but could be useful in detecting moderate chronic renal disease. |
| 156 | 16394503 | MCTF treatment activated caspase-8, -9 and -3, and led to cleaved poly (ADP-ribose) polymerase and release of cytochrome c into cytosol in a concentration-dependent manner, while MCTF did not affect Bax or Bcl-2 protein levels as shown by Western blot analysis. |
| 157 | 16554480 | Human astrocytes are resistant to Fas ligand and tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis. |
| 158 | 16554480 | Here, we report that calcium/calmodulin-dependent protein kinase II (CaMKII) is constitutively activated in human astrocytes and protects the cells from apoptotic stimulation by Fas agonist. |
| 159 | 16554480 | Once stimulated, Fas recruits Fas-associated death domain and caspase-8 for the assembly of the death-inducing signaling complex (DISC); however, caspase-8 cleavage is inhibited in the DISC. |
| 160 | 16554480 | Inhibition of CaMKII kinase activity inhibits the expression of phosphoprotein enriched astrocytes-15 kDa/phosphoprotein enriched in diabetes (PEA-15/PED) and cellular Fas-associated death domain-like interleukin-1beta-converting enzyme-inhibitory protein (c-FLIP), thus releasing their inhibition of caspase-8 cleavage. |
| 161 | 16554480 | Inhibition of PEA-15/PED or c-FLIP by small interfering RNA sensitizes human astrocytes to Fas-induced apoptosis. |
| 162 | 16554480 | In contrast, inhibition of CaMKII, PEA-15, or c-FLIP does not affect the sensitivity of human astrocytes to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). |
| 163 | 16554480 | TRAIL death receptors (DR4, DR5) are weakly expressed at mRNA, protein, and cell surface levels and thus fail to mediate the assembly of the DISC in human astrocytes. |
| 164 | 16554480 | Overexpression of DR5 restores TRAIL signaling pathways and sensitizes the human astrocytes to TRAIL-induced apoptosis if CaMKII kinase activity or expression of PEA-15 and c-FLIP is inhibited; the results suggest that CaMKII-mediated pathways prevent TRAIL-induced apoptosis in human astrocytes under conditions in which TRAIL death receptors are upregulated. |
| 165 | 16554480 | This study has therefore identified the molecular mechanisms that protect normal human astrocytes from apoptosis induced by Fas ligand and TRAIL. |
| 166 | 16554480 | Human astrocytes are resistant to Fas ligand and tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis. |
| 167 | 16554480 | Here, we report that calcium/calmodulin-dependent protein kinase II (CaMKII) is constitutively activated in human astrocytes and protects the cells from apoptotic stimulation by Fas agonist. |
| 168 | 16554480 | Once stimulated, Fas recruits Fas-associated death domain and caspase-8 for the assembly of the death-inducing signaling complex (DISC); however, caspase-8 cleavage is inhibited in the DISC. |
| 169 | 16554480 | Inhibition of CaMKII kinase activity inhibits the expression of phosphoprotein enriched astrocytes-15 kDa/phosphoprotein enriched in diabetes (PEA-15/PED) and cellular Fas-associated death domain-like interleukin-1beta-converting enzyme-inhibitory protein (c-FLIP), thus releasing their inhibition of caspase-8 cleavage. |
| 170 | 16554480 | Inhibition of PEA-15/PED or c-FLIP by small interfering RNA sensitizes human astrocytes to Fas-induced apoptosis. |
| 171 | 16554480 | In contrast, inhibition of CaMKII, PEA-15, or c-FLIP does not affect the sensitivity of human astrocytes to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). |
| 172 | 16554480 | TRAIL death receptors (DR4, DR5) are weakly expressed at mRNA, protein, and cell surface levels and thus fail to mediate the assembly of the DISC in human astrocytes. |
| 173 | 16554480 | Overexpression of DR5 restores TRAIL signaling pathways and sensitizes the human astrocytes to TRAIL-induced apoptosis if CaMKII kinase activity or expression of PEA-15 and c-FLIP is inhibited; the results suggest that CaMKII-mediated pathways prevent TRAIL-induced apoptosis in human astrocytes under conditions in which TRAIL death receptors are upregulated. |
| 174 | 16554480 | This study has therefore identified the molecular mechanisms that protect normal human astrocytes from apoptosis induced by Fas ligand and TRAIL. |
| 175 | 16857402 | The first type 2 diabetes (T2D) gene to be identified in a genome wide scan followed by positional cloning was CAPN10 encoding the cysteine protease calpain-10. |
| 176 | 16869889 | Activation of activating transcription factor 2 by p38 MAP kinase during apoptosis induced by human amylin in cultured pancreatic beta-cells. |
| 177 | 16869889 | We previously reported that fibrillogenic human amylin (hA) evokes beta-cell apoptosis through linked activation of Jun N-terminal kinase 1 (JNK 1) and a caspase cascade. |
| 178 | 16869889 | Here we show that p38 kinase [p38 mitogen-activated protein (MAP) kinase] became activated by hA treatment of cultured beta-cells whereas extracellular signal-regulated kinase (ERK) did not; by contrast, nonfibrillogenic rat amylin (rA) altered neither. |
| 179 | 16869889 | Pretreatment with the p38 kinase-inhibitor SB203580 decreased hA-induced apoptosis and caspase-3 activation by approximately 30%; as did combined SB203580 and JNK inhibitor I, by about 70%; and the combination of SB203580, the JNK inhibitor I and a caspase-8 inhibitor, by 100%. |
| 180 | 16869889 | These findings demonstrate the requirement for concurrent activation of the p38 kinase, JNK and caspase-8 pathways. |
| 181 | 16869889 | We further showed that hA elicits time-dependent activation of activating transcription factor 2 (ATF-2), which was largely suppressed by SB203580, indicating that this activation is catalyzed mainly by p38 kinase. |
| 182 | 16869889 | Furthermore, hA-induced apoptosis was suppressed by specific antisense ATF-2, and increased phospho-ATF-2 (p-ATF-2) was associated with increased CRE (cAMP-response element) DNA binding and CRE-mediated transcriptional activity, as well as enhancement of c-jun promoter activation. |
| 183 | 16869889 | These studies establish p38 MAP kinase-mediated activation of ATF-2 as a significant mechanism in hA-evoked beta-cell death, which may serve as a target for pharmaceutical intervention and effective suppression of beta-cell failure in type-2 diabetes. |
| 184 | 16869889 | Activation of activating transcription factor 2 by p38 MAP kinase during apoptosis induced by human amylin in cultured pancreatic beta-cells. |
| 185 | 16869889 | We previously reported that fibrillogenic human amylin (hA) evokes beta-cell apoptosis through linked activation of Jun N-terminal kinase 1 (JNK 1) and a caspase cascade. |
| 186 | 16869889 | Here we show that p38 kinase [p38 mitogen-activated protein (MAP) kinase] became activated by hA treatment of cultured beta-cells whereas extracellular signal-regulated kinase (ERK) did not; by contrast, nonfibrillogenic rat amylin (rA) altered neither. |
| 187 | 16869889 | Pretreatment with the p38 kinase-inhibitor SB203580 decreased hA-induced apoptosis and caspase-3 activation by approximately 30%; as did combined SB203580 and JNK inhibitor I, by about 70%; and the combination of SB203580, the JNK inhibitor I and a caspase-8 inhibitor, by 100%. |
| 188 | 16869889 | These findings demonstrate the requirement for concurrent activation of the p38 kinase, JNK and caspase-8 pathways. |
| 189 | 16869889 | We further showed that hA elicits time-dependent activation of activating transcription factor 2 (ATF-2), which was largely suppressed by SB203580, indicating that this activation is catalyzed mainly by p38 kinase. |
| 190 | 16869889 | Furthermore, hA-induced apoptosis was suppressed by specific antisense ATF-2, and increased phospho-ATF-2 (p-ATF-2) was associated with increased CRE (cAMP-response element) DNA binding and CRE-mediated transcriptional activity, as well as enhancement of c-jun promoter activation. |
| 191 | 16869889 | These studies establish p38 MAP kinase-mediated activation of ATF-2 as a significant mechanism in hA-evoked beta-cell death, which may serve as a target for pharmaceutical intervention and effective suppression of beta-cell failure in type-2 diabetes. |
| 192 | 17003335 | Fas, a death receptor regulated by IL-1beta, is involved in glucose-induced beta-cell apoptosis. |
| 193 | 17003335 | Fas engagement can be switched from death signal to induction of proliferation when the caspase 8 inhibitor, FLICE-inhibitory protein (FLIP), is active. |
| 194 | 17003335 | A similarly bimodal induction of FLIP, pancreatic duodenal homeobox (PDX)-1, and Pax4 mRNA expression, as well as glucose-stimulated insulin secretion, was observed. |
| 195 | 17003335 | In contrast, Fas induction by IL-1beta was monophasic. |
| 196 | 17003335 | Low IL-1beta also induced the IL-1 receptor antagonist (IL-1Ra), suppression of which by RNA interference abrogated the beneficial effects of low IL-1beta. |
| 197 | 17003335 | Consistent with our in vitro results, IL-1beta knockout mice displayed glucose intolerance along with a decrease in islet Fas, FLIP, Pax4, and PDX-1 transcripts. |
| 198 | 17003335 | These findings indicate that low IL-1beta levels positively influence beta-cell function and turnover through the Fas-FLIP pathway and that IL-1Ra production prevents harmful effects of high IL-1beta concentrations. |
| 199 | 17064973 | Advanced glycation end products stimulate osteoblast apoptosis via the MAP kinase and cytosolic apoptotic pathways. |
| 200 | 17064973 | CML-collagen increased p38 and JNK activity 3.2- and 4.4-fold, respectively. |
| 201 | 17064973 | Inhibition of p38 and JNK reduced CML-collagen stimulated apoptosis by 45% and 59% and by 90% when used together (P<0.05). |
| 202 | 17064973 | The predominant apoptotic pathway induced by CML-collagen involved caspase-8 activation of caspase-3 and was independent of NF-kappaB activation. |
| 203 | 17065389 | Cell death was significantly increased after 4 weeks, as was caspase-8 activation, although circulating levels of TNF-alpha were increased as early as 1 week. |
| 204 | 17151322 | Positional cloning studies mapped T2DM susceptibility to CAPN10, the gene encoding the intracellular cysteine protease, calpain 10. |
| 205 | 17151322 | Here we review recent studies, which in addition to the latter enzyme, have linked calpain 5, calpain 3, and its splice variants, calpain 2 and calpain 1 to T2DM-related metabolic pathways along with T2DM-associated phenotypes, such as obesity and impaired insulin secretion, and T2DM-related complications, such as epithelial dysfunction and diabetic cataract. |
| 206 | 17299038 | Fas is a death receptor involved in beta cell apoptosis or proliferation, depending on the activity of the caspase-8 inhibitor FLIP. |
| 207 | 17299038 | Expression of PDX-1, a beta cell-specific transcription factor regulating insulin gene expression and mitochondrial metabolism, was decreased in Fas-deficient beta cells. |
| 208 | 17299038 | This led to increased PDX-1 and insulin production independent of changes in cell turnover. |
| 209 | 17299038 | The results support a previously undescribed role for the Fas pathway in regulating insulin production and release. |
| 210 | 17563067 | We show that islets isolated from RIPcre(+)Casp8(fl/fl) mice were protected from Fas ligand (FasL)-and ceramide-induced cell death. |
| 211 | 17563067 | Their islets display decreased expression of molecules involved in insulin/IGF-I signaling and show decreased pancreatic duodenal homeobox-1 and cAMP response element binding protein expression. |
| 212 | 17563067 | Our results show distinct context-specific roles of Casp8 in physiological and disease states; Casp8 is essential for beta-cell apoptosis in type 1 and type 2 diabetes models and in regulating beta-cell mass and insulin secretion under physiological conditions. |
| 213 | 17563067 | We show that islets isolated from RIPcre(+)Casp8(fl/fl) mice were protected from Fas ligand (FasL)-and ceramide-induced cell death. |
| 214 | 17563067 | Their islets display decreased expression of molecules involved in insulin/IGF-I signaling and show decreased pancreatic duodenal homeobox-1 and cAMP response element binding protein expression. |
| 215 | 17563067 | Our results show distinct context-specific roles of Casp8 in physiological and disease states; Casp8 is essential for beta-cell apoptosis in type 1 and type 2 diabetes models and in regulating beta-cell mass and insulin secretion under physiological conditions. |
| 216 | 17869649 | The CTSL2 gene encodes the cysteine protease cathepsin V involved in antigen presentation in human cortical thymic epithelial cells, and involvement of the protease in autoimmunity has been suggested. |
| 217 | 18619973 | As we have recently shown, expression and activity of the matrix degrading cysteine protease cathepsin L in EPC is required for tissue invasion and EPC-mediated improvement of neovascularization. |
| 218 | 18619973 | In contrast, other proteases of the cathepsin family such as cathepsins D and O, and the matrix metalloproteinases MMP-2 and MMP-9 were not altered with high glucose. |
| 219 | 19194987 | Inhibition of caspase-8 activity also reduced hyperglycemia-induced Bid activation and caspase-9 cleavage. |
| 220 | 19194987 | These data suggest that caspase-8 may control diabetic embryopathy-associated apoptosis via regulation of the Bid-stimulated mitochondrion/caspase-9 pathway. |
| 221 | 19194987 | Inhibition of caspase-8 activity also reduced hyperglycemia-induced Bid activation and caspase-9 cleavage. |
| 222 | 19194987 | These data suggest that caspase-8 may control diabetic embryopathy-associated apoptosis via regulation of the Bid-stimulated mitochondrion/caspase-9 pathway. |
| 223 | 19297292 | Calpaïn 10 (CAPN10) is the first diabetes gene to be identified through a genome scan followed by positional cloning, encoding the cysteine protease, the calpaïn 10 encodes for a ubiquitously expressed protease implicated in the two fundamental pathophysiological aspects of T2DM insulinoresistance and insulinosecretion. |
| 224 | 19432816 | DR5-mediated DISC controls caspase-8 cleavage and initiation of apoptosis in human glioblastomas. |
| 225 | 19432816 | TRAIL has four membrane-anchored receptors, death receptor 4/5 (DR4/5) and decoy receptor 1/2 (DcR1/2). |
| 226 | 19432816 | Of these receptors, only DR5 was expressed consistently in glioblastoma cell lines and tumour tissues, ruling out the role of DcR1/2 in TRAIL resistance. |
| 227 | 19432816 | Upon TRAIL binding, DR5 was homotrimerized and recruited Fas-associated death domain (FADD) and caspase-8 for the assembly of death-inducing signalling complex (DISC) in the lipid rafts of the plasma membrane. |
| 228 | 19432816 | In the DISC, caspase-8 was cleaved and initiated apoptosis by cleaving downstream caspases in TRAIL-sensitive glioblastoma cells. |
| 229 | 19432816 | In TRAIL-resistant cells, however, DR5-mediated DISC was modified by receptor-interacting protein (RIP), cellular FADD-like interleukin-1beta-converting enzyme inhibitory protein (c-FLIP) and phosphoprotein enriched in diabetes or in astrocyte-15 (PED/PEA-15). |
| 230 | 19432816 | This DISC modification occurred in the non-raft fractions of the plasma membrane and resulted in the inhibition of caspase-8 cleavage and activation of nuclear factor-kappaB (NF-kappaB). |
| 231 | 19432816 | Treatment of resistant cells with parthenolide, an inhibitor of inhibitor of kappaB (I-kappaB), eliminated TRAIL-induced NF-kappaB activity but not TRAIL resistance. |
| 232 | 19432816 | In contrast, however, targeting of RIP, c-FLIP or PED/PEA-15 with small interfering RNA (siRNA) led to the redistribution of the DISC from non-rafts to lipid rafts and eliminated the inhibition of caspase-8 cleavage and thereby TRAIL resistance. |
| 233 | 19432816 | Taken together, this study indicates that the DISC modification by RIP, c-FLIP and PED/PEA-15 is the most upstream event in TRAIL resistance in glioblastomas. |
| 234 | 19432816 | DR5-mediated DISC controls caspase-8 cleavage and initiation of apoptosis in human glioblastomas. |
| 235 | 19432816 | TRAIL has four membrane-anchored receptors, death receptor 4/5 (DR4/5) and decoy receptor 1/2 (DcR1/2). |
| 236 | 19432816 | Of these receptors, only DR5 was expressed consistently in glioblastoma cell lines and tumour tissues, ruling out the role of DcR1/2 in TRAIL resistance. |
| 237 | 19432816 | Upon TRAIL binding, DR5 was homotrimerized and recruited Fas-associated death domain (FADD) and caspase-8 for the assembly of death-inducing signalling complex (DISC) in the lipid rafts of the plasma membrane. |
| 238 | 19432816 | In the DISC, caspase-8 was cleaved and initiated apoptosis by cleaving downstream caspases in TRAIL-sensitive glioblastoma cells. |
| 239 | 19432816 | In TRAIL-resistant cells, however, DR5-mediated DISC was modified by receptor-interacting protein (RIP), cellular FADD-like interleukin-1beta-converting enzyme inhibitory protein (c-FLIP) and phosphoprotein enriched in diabetes or in astrocyte-15 (PED/PEA-15). |
| 240 | 19432816 | This DISC modification occurred in the non-raft fractions of the plasma membrane and resulted in the inhibition of caspase-8 cleavage and activation of nuclear factor-kappaB (NF-kappaB). |
| 241 | 19432816 | Treatment of resistant cells with parthenolide, an inhibitor of inhibitor of kappaB (I-kappaB), eliminated TRAIL-induced NF-kappaB activity but not TRAIL resistance. |
| 242 | 19432816 | In contrast, however, targeting of RIP, c-FLIP or PED/PEA-15 with small interfering RNA (siRNA) led to the redistribution of the DISC from non-rafts to lipid rafts and eliminated the inhibition of caspase-8 cleavage and thereby TRAIL resistance. |
| 243 | 19432816 | Taken together, this study indicates that the DISC modification by RIP, c-FLIP and PED/PEA-15 is the most upstream event in TRAIL resistance in glioblastomas. |
| 244 | 19432816 | DR5-mediated DISC controls caspase-8 cleavage and initiation of apoptosis in human glioblastomas. |
| 245 | 19432816 | TRAIL has four membrane-anchored receptors, death receptor 4/5 (DR4/5) and decoy receptor 1/2 (DcR1/2). |
| 246 | 19432816 | Of these receptors, only DR5 was expressed consistently in glioblastoma cell lines and tumour tissues, ruling out the role of DcR1/2 in TRAIL resistance. |
| 247 | 19432816 | Upon TRAIL binding, DR5 was homotrimerized and recruited Fas-associated death domain (FADD) and caspase-8 for the assembly of death-inducing signalling complex (DISC) in the lipid rafts of the plasma membrane. |
| 248 | 19432816 | In the DISC, caspase-8 was cleaved and initiated apoptosis by cleaving downstream caspases in TRAIL-sensitive glioblastoma cells. |
| 249 | 19432816 | In TRAIL-resistant cells, however, DR5-mediated DISC was modified by receptor-interacting protein (RIP), cellular FADD-like interleukin-1beta-converting enzyme inhibitory protein (c-FLIP) and phosphoprotein enriched in diabetes or in astrocyte-15 (PED/PEA-15). |
| 250 | 19432816 | This DISC modification occurred in the non-raft fractions of the plasma membrane and resulted in the inhibition of caspase-8 cleavage and activation of nuclear factor-kappaB (NF-kappaB). |
| 251 | 19432816 | Treatment of resistant cells with parthenolide, an inhibitor of inhibitor of kappaB (I-kappaB), eliminated TRAIL-induced NF-kappaB activity but not TRAIL resistance. |
| 252 | 19432816 | In contrast, however, targeting of RIP, c-FLIP or PED/PEA-15 with small interfering RNA (siRNA) led to the redistribution of the DISC from non-rafts to lipid rafts and eliminated the inhibition of caspase-8 cleavage and thereby TRAIL resistance. |
| 253 | 19432816 | Taken together, this study indicates that the DISC modification by RIP, c-FLIP and PED/PEA-15 is the most upstream event in TRAIL resistance in glioblastomas. |
| 254 | 19432816 | DR5-mediated DISC controls caspase-8 cleavage and initiation of apoptosis in human glioblastomas. |
| 255 | 19432816 | TRAIL has four membrane-anchored receptors, death receptor 4/5 (DR4/5) and decoy receptor 1/2 (DcR1/2). |
| 256 | 19432816 | Of these receptors, only DR5 was expressed consistently in glioblastoma cell lines and tumour tissues, ruling out the role of DcR1/2 in TRAIL resistance. |
| 257 | 19432816 | Upon TRAIL binding, DR5 was homotrimerized and recruited Fas-associated death domain (FADD) and caspase-8 for the assembly of death-inducing signalling complex (DISC) in the lipid rafts of the plasma membrane. |
| 258 | 19432816 | In the DISC, caspase-8 was cleaved and initiated apoptosis by cleaving downstream caspases in TRAIL-sensitive glioblastoma cells. |
| 259 | 19432816 | In TRAIL-resistant cells, however, DR5-mediated DISC was modified by receptor-interacting protein (RIP), cellular FADD-like interleukin-1beta-converting enzyme inhibitory protein (c-FLIP) and phosphoprotein enriched in diabetes or in astrocyte-15 (PED/PEA-15). |
| 260 | 19432816 | This DISC modification occurred in the non-raft fractions of the plasma membrane and resulted in the inhibition of caspase-8 cleavage and activation of nuclear factor-kappaB (NF-kappaB). |
| 261 | 19432816 | Treatment of resistant cells with parthenolide, an inhibitor of inhibitor of kappaB (I-kappaB), eliminated TRAIL-induced NF-kappaB activity but not TRAIL resistance. |
| 262 | 19432816 | In contrast, however, targeting of RIP, c-FLIP or PED/PEA-15 with small interfering RNA (siRNA) led to the redistribution of the DISC from non-rafts to lipid rafts and eliminated the inhibition of caspase-8 cleavage and thereby TRAIL resistance. |
| 263 | 19432816 | Taken together, this study indicates that the DISC modification by RIP, c-FLIP and PED/PEA-15 is the most upstream event in TRAIL resistance in glioblastomas. |
| 264 | 19432816 | DR5-mediated DISC controls caspase-8 cleavage and initiation of apoptosis in human glioblastomas. |
| 265 | 19432816 | TRAIL has four membrane-anchored receptors, death receptor 4/5 (DR4/5) and decoy receptor 1/2 (DcR1/2). |
| 266 | 19432816 | Of these receptors, only DR5 was expressed consistently in glioblastoma cell lines and tumour tissues, ruling out the role of DcR1/2 in TRAIL resistance. |
| 267 | 19432816 | Upon TRAIL binding, DR5 was homotrimerized and recruited Fas-associated death domain (FADD) and caspase-8 for the assembly of death-inducing signalling complex (DISC) in the lipid rafts of the plasma membrane. |
| 268 | 19432816 | In the DISC, caspase-8 was cleaved and initiated apoptosis by cleaving downstream caspases in TRAIL-sensitive glioblastoma cells. |
| 269 | 19432816 | In TRAIL-resistant cells, however, DR5-mediated DISC was modified by receptor-interacting protein (RIP), cellular FADD-like interleukin-1beta-converting enzyme inhibitory protein (c-FLIP) and phosphoprotein enriched in diabetes or in astrocyte-15 (PED/PEA-15). |
| 270 | 19432816 | This DISC modification occurred in the non-raft fractions of the plasma membrane and resulted in the inhibition of caspase-8 cleavage and activation of nuclear factor-kappaB (NF-kappaB). |
| 271 | 19432816 | Treatment of resistant cells with parthenolide, an inhibitor of inhibitor of kappaB (I-kappaB), eliminated TRAIL-induced NF-kappaB activity but not TRAIL resistance. |
| 272 | 19432816 | In contrast, however, targeting of RIP, c-FLIP or PED/PEA-15 with small interfering RNA (siRNA) led to the redistribution of the DISC from non-rafts to lipid rafts and eliminated the inhibition of caspase-8 cleavage and thereby TRAIL resistance. |
| 273 | 19432816 | Taken together, this study indicates that the DISC modification by RIP, c-FLIP and PED/PEA-15 is the most upstream event in TRAIL resistance in glioblastomas. |
| 274 | 19467786 | We previously reported that high glucose can induce apoptosis in PC12 cells, as evidenced by DNA fragmentation and high Bax/Bcl-2 ratio. |
| 275 | 19467786 | The present study examined the involvement of caspase-3, the executioner, and two initiators of apoptosis, caspase-8 and caspase-9, during high glucose-induced apoptosis in PC12 cells, a neuronal cell line. |
| 276 | 19540304 | Ghrelin did not modify body weight or serum glucose, leptin or adiponectin, but increased total ghrelin (P<0.05), IGF-I (P<0.01) and prolactin (P<0.01) levels. |
| 277 | 19540304 | Ghrelin decreased cell death, iNOS and active caspase-8 (P<0.05) and increased prolactin (P<0.05), Bcl-2 (P<0.01) and Hsp70 (P<0.05) content in the pituitary. |
| 278 | 19540304 | In conclusion, ghrelin prevents diabetes-induced death of lactotrophs, decreasing caspase-8 activation and iNOS content and increasing anti-apoptotic pathways such as pituitary Bcl-2 and Hsp70 and serum IGF-I concentrations. |
| 279 | 19540304 | Ghrelin did not modify body weight or serum glucose, leptin or adiponectin, but increased total ghrelin (P<0.05), IGF-I (P<0.01) and prolactin (P<0.01) levels. |
| 280 | 19540304 | Ghrelin decreased cell death, iNOS and active caspase-8 (P<0.05) and increased prolactin (P<0.05), Bcl-2 (P<0.01) and Hsp70 (P<0.05) content in the pituitary. |
| 281 | 19540304 | In conclusion, ghrelin prevents diabetes-induced death of lactotrophs, decreasing caspase-8 activation and iNOS content and increasing anti-apoptotic pathways such as pituitary Bcl-2 and Hsp70 and serum IGF-I concentrations. |
| 282 | 19633655 | Adoptive transfer experiments of cytokine-deficient mast cells show that these cells, by producing interleukin-6 (IL-6) and interferon-gamma (IFN-gamma), contribute to mouse adipose tissue cysteine protease cathepsin expression, apoptosis and angiogenesis, thereby promoting diet-induced obesity and glucose intolerance. |
| 283 | 20200974 | TNF-alpha mediates diabetes-enhanced chondrocyte apoptosis during fracture healing and stimulates chondrocyte apoptosis through FOXO1. |
| 284 | 20200974 | Tumor necrosis factor alpha (TNF-alpha) protein levels were assessed by ELISA and caspase-3 by bioactivity assay. |
| 285 | 20200974 | In vitro studies investigated the proapoptotic transcription factor FOXO1 in regulating TNF-induced apoptosis of chondrogenic ATDC5 and C3H10T1/2 cells as representative of differentiated chondrocytes, which are important during endochondral ossification. mRNA profiling revealed an upregulation of gene sets related to apoptosis in the diabetic group on day 16 when cartilage resorption is active but not day 12 or day 22. |
| 286 | 20200974 | This coincided with elevated TNF-alpha protein levels, chondrocyte apoptosis, enhanced caspase-3 activity, and increased FOXO1 nuclear translocation (p < .05). |
| 287 | 20200974 | Silencing FOXO1 using siRNA in vitro significantly reduced TNF-induced apoptosis and caspase activity in differentiated chondrocytes. |
| 288 | 20200974 | The mRNA levels of the proapoptotic genes caspase-3, caspase-8, caspase-9, and TRAIL were significantly reduced with silencing of FOXO1 in chondrocytic cells. |
| 289 | 20200974 | Inhibiting caspase-8 and caspase-9 significantly reduced TNF-induced apoptosis in chondrogenic cells. |
| 290 | 20200974 | Diabetes increased chondrocyte apoptosis through a mechanism that involved enhanced production of TNF-alpha, which stimulates chondrocyte apoptosis and upregulates mRNA levels of apoptotic genes through FOXO1 activation. |
| 291 | 20200974 | TNF-alpha mediates diabetes-enhanced chondrocyte apoptosis during fracture healing and stimulates chondrocyte apoptosis through FOXO1. |
| 292 | 20200974 | Tumor necrosis factor alpha (TNF-alpha) protein levels were assessed by ELISA and caspase-3 by bioactivity assay. |
| 293 | 20200974 | In vitro studies investigated the proapoptotic transcription factor FOXO1 in regulating TNF-induced apoptosis of chondrogenic ATDC5 and C3H10T1/2 cells as representative of differentiated chondrocytes, which are important during endochondral ossification. mRNA profiling revealed an upregulation of gene sets related to apoptosis in the diabetic group on day 16 when cartilage resorption is active but not day 12 or day 22. |
| 294 | 20200974 | This coincided with elevated TNF-alpha protein levels, chondrocyte apoptosis, enhanced caspase-3 activity, and increased FOXO1 nuclear translocation (p < .05). |
| 295 | 20200974 | Silencing FOXO1 using siRNA in vitro significantly reduced TNF-induced apoptosis and caspase activity in differentiated chondrocytes. |
| 296 | 20200974 | The mRNA levels of the proapoptotic genes caspase-3, caspase-8, caspase-9, and TRAIL were significantly reduced with silencing of FOXO1 in chondrocytic cells. |
| 297 | 20200974 | Inhibiting caspase-8 and caspase-9 significantly reduced TNF-induced apoptosis in chondrogenic cells. |
| 298 | 20200974 | Diabetes increased chondrocyte apoptosis through a mechanism that involved enhanced production of TNF-alpha, which stimulates chondrocyte apoptosis and upregulates mRNA levels of apoptotic genes through FOXO1 activation. |
| 299 | 20227390 | Pretreatment with rosiglitazone also suppressed radiation-induced H2AX phosphorylation in response to DNA damage and AKT activation for cell survival; on the contrary, rosiglitazone pretreatment enhanced radiation-induced caspase-8, -9, and -3 activation and PARP cleavage in HT-29 cells. |
| 300 | 21076025 | Activity of the intrinsic apoptosis pathway mediator caspase-9 was greater in diabetic atrial tissue, whereas activity of the extrinsic pathway mediator caspase-8 was unchanged between groups. |
| 301 | 21186369 | The adipocyte-derived secretory factor adiponectin promotes insulin sensitivity, decreases inflammation and promotes cell survival. |
| 302 | 21186369 | Here, we show that adiponectin potently stimulates a ceramidase activity associated with its two receptors, AdipoR1 and AdipoR2, and enhances ceramide catabolism and formation of its antiapoptotic metabolite--sphingosine-1-phosphate (S1P)--independently of AMP-dependent kinase (AMPK). |
| 303 | 21186369 | Using models of inducible apoptosis in pancreatic beta cells and cardiomyocytes, we show that transgenic overproduction of adiponectin decreases caspase-8-mediated death, whereas genetic ablation of adiponectin enhances apoptosis in vivo through a sphingolipid-mediated pathway. |
| 304 | 21523780 | Limited proteolysis can take place extracellularly by serine proteases, released in particular by infiltrating neutrophils or intracellularly by the cysteine protease caspase-1. |
| 305 | 21691071 | Caspase 3 is activated through caspase 8 instead of caspase 9 during H2O2-induced apoptosis in HeLa cells. |
| 306 | 21691071 | We measured the activation dynamics of caspase 3 and caspase 9 based on two reporter systems, SCAT 3 and SCAT 9. |
| 307 | 21691071 | We found that caspase 3 activation was earlier than that of caspase 9 following H(2)O(2) treatment. |
| 308 | 21691071 | Caspase 3 was activated rapidly, reaching a maximum in 12±3 min, while the average duration of caspase 9 activation was 21±3 min. |
| 309 | 21691071 | When cells were pretreated with Z-LEHD-fmk, a caspase 9 specific inhibitor, caspase 3 activation and apoptosis by H(2)O(2) treatment were little affected, although the caspase 9 activation was completely inhibited. |
| 310 | 21691071 | When cells were pretreated with Z-DEVD-fmk, a caspase 3 specific inhibitor, the activation of both caspase 3 and caspase 9, as well as apoptosis, were inhibited. |
| 311 | 21691071 | When cells were pretreated with Z-IETD-fmk, a caspase 8 specific inhibitor, the activation of caspase 3 and caspase 9 were significantly delayed. |
| 312 | 21691071 | Our results suggest that, during H H(2)O(2)-induced apoptosis, caspase 3 is activated directly through caspase 8 and is not through the mitochondria-dependent caspase 9 activation. |
| 313 | 21691071 | Caspase 3 is activated through caspase 8 instead of caspase 9 during H2O2-induced apoptosis in HeLa cells. |
| 314 | 21691071 | We measured the activation dynamics of caspase 3 and caspase 9 based on two reporter systems, SCAT 3 and SCAT 9. |
| 315 | 21691071 | We found that caspase 3 activation was earlier than that of caspase 9 following H(2)O(2) treatment. |
| 316 | 21691071 | Caspase 3 was activated rapidly, reaching a maximum in 12±3 min, while the average duration of caspase 9 activation was 21±3 min. |
| 317 | 21691071 | When cells were pretreated with Z-LEHD-fmk, a caspase 9 specific inhibitor, caspase 3 activation and apoptosis by H(2)O(2) treatment were little affected, although the caspase 9 activation was completely inhibited. |
| 318 | 21691071 | When cells were pretreated with Z-DEVD-fmk, a caspase 3 specific inhibitor, the activation of both caspase 3 and caspase 9, as well as apoptosis, were inhibited. |
| 319 | 21691071 | When cells were pretreated with Z-IETD-fmk, a caspase 8 specific inhibitor, the activation of caspase 3 and caspase 9 were significantly delayed. |
| 320 | 21691071 | Our results suggest that, during H H(2)O(2)-induced apoptosis, caspase 3 is activated directly through caspase 8 and is not through the mitochondria-dependent caspase 9 activation. |
| 321 | 21691071 | Caspase 3 is activated through caspase 8 instead of caspase 9 during H2O2-induced apoptosis in HeLa cells. |
| 322 | 21691071 | We measured the activation dynamics of caspase 3 and caspase 9 based on two reporter systems, SCAT 3 and SCAT 9. |
| 323 | 21691071 | We found that caspase 3 activation was earlier than that of caspase 9 following H(2)O(2) treatment. |
| 324 | 21691071 | Caspase 3 was activated rapidly, reaching a maximum in 12±3 min, while the average duration of caspase 9 activation was 21±3 min. |
| 325 | 21691071 | When cells were pretreated with Z-LEHD-fmk, a caspase 9 specific inhibitor, caspase 3 activation and apoptosis by H(2)O(2) treatment were little affected, although the caspase 9 activation was completely inhibited. |
| 326 | 21691071 | When cells were pretreated with Z-DEVD-fmk, a caspase 3 specific inhibitor, the activation of both caspase 3 and caspase 9, as well as apoptosis, were inhibited. |
| 327 | 21691071 | When cells were pretreated with Z-IETD-fmk, a caspase 8 specific inhibitor, the activation of caspase 3 and caspase 9 were significantly delayed. |
| 328 | 21691071 | Our results suggest that, during H H(2)O(2)-induced apoptosis, caspase 3 is activated directly through caspase 8 and is not through the mitochondria-dependent caspase 9 activation. |
| 329 | 21719578 | To this end, we examined the role of cytochrome c in pancreatic β-cells under homeostatic conditions and in diabetes models, including those induced by streptozotocin (STZ) and c-Myc. |
| 330 | 21719578 | Previous studies have shown that both STZ- and c-Myc-induced β-cell apoptosis is mediated through caspase-3 activation; however, the precise mechanism in these modes of cell death was not characterized. |
| 331 | 21719578 | Moreover, the cytochrome c-mediated intrinsic apoptotic pathway is required for neither STZ- nor c-Myc-induced β-cell death. |
| 332 | 21719578 | We also observed that the extrinsic apoptotic pathway mediated through caspase-8 was not essential in c-Myc-induced β-cell destruction. |
| 333 | 21719578 | These findings suggest that cytochrome c is not required for STZ-induced β-cell apoptosis and, together with the caspase-8-mediated extrinsic pathway, plays a redundant role in c-Myc-induced β-cell apoptosis. |
| 334 | 21719578 | To this end, we examined the role of cytochrome c in pancreatic β-cells under homeostatic conditions and in diabetes models, including those induced by streptozotocin (STZ) and c-Myc. |
| 335 | 21719578 | Previous studies have shown that both STZ- and c-Myc-induced β-cell apoptosis is mediated through caspase-3 activation; however, the precise mechanism in these modes of cell death was not characterized. |
| 336 | 21719578 | Moreover, the cytochrome c-mediated intrinsic apoptotic pathway is required for neither STZ- nor c-Myc-induced β-cell death. |
| 337 | 21719578 | We also observed that the extrinsic apoptotic pathway mediated through caspase-8 was not essential in c-Myc-induced β-cell destruction. |
| 338 | 21719578 | These findings suggest that cytochrome c is not required for STZ-induced β-cell apoptosis and, together with the caspase-8-mediated extrinsic pathway, plays a redundant role in c-Myc-induced β-cell apoptosis. |
| 339 | 22138721 | The aim of this study was to investigate (i) the cholecystokinin, somatostatin and apelin mRNA levels, (ii) the changes in levels and localization of these peptides, (iii) relation between these peptides, (iv) antiapoptotic effects and (v) antioxidant effects of ghrelin. |
| 340 | 22138721 | Cholecystokinin mRNA and peptide, somatostatin mRNA, release to duodenal lumen of apelin peptide and apelin mRNA signals decreased in ghrelin-treated diabetic rats compared to the diabetic group. |
| 341 | 22138721 | There was no statistically significant difference among the four groups for somatostatin and apelin peptides. |
| 342 | 22138721 | Caspase-3 signals were not observed only in diabetic group treated with ghrelin. |
| 343 | 22138721 | Caspase-8 signals were increased while PCNA signals were decreased in diabetic group given ghrelin compared to diabetic group. |
| 344 | 22138721 | Small intestine CAT, SOD, GP(x) and GST activities and GSH levels were decreased and LPO, PC levels were increased in diabetic rats. |
| 345 | 22155658 | Further, western blot analysis revealed the activation of caspases family proteins viz., caspase 8, caspase-9 and caspase-3. |
| 346 | 22155658 | An increase in the expression of Bax mRNA concomitant with a decrease in mRNA of Bcl-2 in BEHP treated K562 cells was also observed. |
| 347 | 22612451 | Calpain 10 is a ubiquitously expressed mitochondrial and cytosolic Ca(2+)-regulated cysteine protease in which overexpression or knockdown leads to mitochondrial dysfunction and cell death. |
| 348 | 22612451 | Therefore, we created a homology model using the calpain 10 amino acid sequence and calpain 1 3-D structure and docked CYGAK in the active site. |
| 349 | 22612451 | RPTC treated with 10 μM CYGAK-OC for 24 h induced accumulation of ATP synthase β and NDUFB8, two calpain 10 substrates. |
| 350 | 22820249 | Profound conformational changes of PED/PEA-15 in ERK2 complex revealed by NMR backbone dynamics. |
| 351 | 22820249 | PED/PEA-15 is a small, non-catalytic, DED containing protein that is widely expressed in different tissues and highly conserved among mammals. |
| 352 | 22820249 | PED/PEA-15 has been found to interact with several protein targets in various pathways, including FADD and procaspase-8 (apoptosis), ERK1/2 (cell cycle entry), and PLD1/2 (diabetes). |
| 353 | 22820249 | In this research, we have studied the PED/PEA-15 in a complex with ERK2, a MAP kinase, using NMR spectroscopic techniques. |
| 354 | 22820249 | MAP Kinase signaling pathways are involved in the regulation of many cellular functions, including cell proliferation, differentiation, apoptosis and survival. |
| 355 | 22820249 | Previous studies have shown that PED/PEA-15 complexes with ERK2 in the cytoplasm and prevents redistribution into the nucleus. |
| 356 | 22820249 | Here we report NMR chemical shift perturbation and backbone dynamic studies at the fast ps-ns timescale of PED/PEA-15, in its free form and in the complex with ERK2. |
| 357 | 22820249 | These analyses characterize motions and conformational changes involved in ERK2 recognition and binding that orchestrate the reorganization of the DED and immobilization of the C-terminal tail. |
| 358 | 22961085 | Embryos exposed to high glucose exhibit aberrant maturational and cytoarchitectural cellular changes, implicating cellular organelle stress in diabetic embryopathy. c-Jun-N-terminal kinase 1/2 (JNK1/2) activation is a causal event in maternal diabetes-induced neural tube defects (NTD). |
| 359 | 22961085 | In embryos cultured under high-glucose conditions (20 mmol/L), the use of 4-phenylbutyric acid (4-PBA), an ER chemical chaperone, diminished ER stress markers and abolished the activation of JNK1/2 and its downstream transcription factors, caspase 3 and caspase 8, and Sox1 neural progenitor apoptosis. |
| 360 | 23238821 | The apoptosis and senescence of NP cells was investigated by terminal deoxyribonucleotidyl transferase (TDT)-mediated dUTP-digoxigenin nick end labeling (TUNEL) assay, immunohistochemistry, and Western blot for caspase3, caspase8, caspase9, and p16lnk4A (increased in cellular senescence). |
| 361 | 23238821 | The proteoglycan and collagen II in the extracellular matrix and the aggrecan and collagen II mRNA expression in NP cells of diabetic rats were decreased compared with the control group. |
| 362 | 23238821 | Diabetes increased apoptosis of NP cells and led to activations of initiators of intrinsic (caspases-9) and extrinsic (caspase-8) pathways as well as their common executioner (caspase-3). |
| 363 | 23238821 | The apoptosis and senescence of NP cells was investigated by terminal deoxyribonucleotidyl transferase (TDT)-mediated dUTP-digoxigenin nick end labeling (TUNEL) assay, immunohistochemistry, and Western blot for caspase3, caspase8, caspase9, and p16lnk4A (increased in cellular senescence). |
| 364 | 23238821 | The proteoglycan and collagen II in the extracellular matrix and the aggrecan and collagen II mRNA expression in NP cells of diabetic rats were decreased compared with the control group. |
| 365 | 23238821 | Diabetes increased apoptosis of NP cells and led to activations of initiators of intrinsic (caspases-9) and extrinsic (caspase-8) pathways as well as their common executioner (caspase-3). |
| 366 | 23255602 | Smad7 protein induces interferon regulatory factor 1-dependent transcriptional activation of caspase 8 to restore tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis. |
| 367 | 23255602 | Smad7 has been known as a negative regulator for the transforming growth factor-β (TGF-β) signaling pathway through feedback regulation. |
| 368 | 23255602 | By screening differentially regulated genes, we found that the caspase 8 gene was highly up-regulated in Smad7-expressing cells. |
| 369 | 23255602 | Smad7 was able to activate the caspase 8 promoter through recruitment of the interferon regulatory factor 1 (IRF1) transcription factor to the interferon-stimulated response element (ISRE) site. |
| 370 | 23255602 | Interaction of Smad7 on the caspase 8 promoter was confirmed with electrophoretic mobility shift assay and chromatin immunoprecipitation experiment. |
| 371 | 23255602 | Interestingly, Smad7 did not directly interact with the ISRE site, but it increased the binding activity of IRF1 with ISRE. |
| 372 | 23255602 | These results support that Smad7 recruits IRF1 protein on the caspase 8 promoter and functions as a transcriptional coactivator. |
| 373 | 23255602 | To confirm the biological significance of caspase 8 up-regulation, we tested tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)-mediated cell death assay in breast cancer cells. |
| 374 | 23255602 | Smad7 in apoptosis-resistant MCF7 cells markedly sensitized the cells to TRAIL-induced cell death by restoring the caspase cascade. |
| 375 | 23255602 | In conclusion, we suggest a novel role for Smad7 as a transcriptional coactivator for caspase 8 through the interaction with IRF1 in regulation of the cell death pathway. |
| 376 | 23255602 | Smad7 protein induces interferon regulatory factor 1-dependent transcriptional activation of caspase 8 to restore tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis. |
| 377 | 23255602 | Smad7 has been known as a negative regulator for the transforming growth factor-β (TGF-β) signaling pathway through feedback regulation. |
| 378 | 23255602 | By screening differentially regulated genes, we found that the caspase 8 gene was highly up-regulated in Smad7-expressing cells. |
| 379 | 23255602 | Smad7 was able to activate the caspase 8 promoter through recruitment of the interferon regulatory factor 1 (IRF1) transcription factor to the interferon-stimulated response element (ISRE) site. |
| 380 | 23255602 | Interaction of Smad7 on the caspase 8 promoter was confirmed with electrophoretic mobility shift assay and chromatin immunoprecipitation experiment. |
| 381 | 23255602 | Interestingly, Smad7 did not directly interact with the ISRE site, but it increased the binding activity of IRF1 with ISRE. |
| 382 | 23255602 | These results support that Smad7 recruits IRF1 protein on the caspase 8 promoter and functions as a transcriptional coactivator. |
| 383 | 23255602 | To confirm the biological significance of caspase 8 up-regulation, we tested tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)-mediated cell death assay in breast cancer cells. |
| 384 | 23255602 | Smad7 in apoptosis-resistant MCF7 cells markedly sensitized the cells to TRAIL-induced cell death by restoring the caspase cascade. |
| 385 | 23255602 | In conclusion, we suggest a novel role for Smad7 as a transcriptional coactivator for caspase 8 through the interaction with IRF1 in regulation of the cell death pathway. |
| 386 | 23255602 | Smad7 protein induces interferon regulatory factor 1-dependent transcriptional activation of caspase 8 to restore tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis. |
| 387 | 23255602 | Smad7 has been known as a negative regulator for the transforming growth factor-β (TGF-β) signaling pathway through feedback regulation. |
| 388 | 23255602 | By screening differentially regulated genes, we found that the caspase 8 gene was highly up-regulated in Smad7-expressing cells. |
| 389 | 23255602 | Smad7 was able to activate the caspase 8 promoter through recruitment of the interferon regulatory factor 1 (IRF1) transcription factor to the interferon-stimulated response element (ISRE) site. |
| 390 | 23255602 | Interaction of Smad7 on the caspase 8 promoter was confirmed with electrophoretic mobility shift assay and chromatin immunoprecipitation experiment. |
| 391 | 23255602 | Interestingly, Smad7 did not directly interact with the ISRE site, but it increased the binding activity of IRF1 with ISRE. |
| 392 | 23255602 | These results support that Smad7 recruits IRF1 protein on the caspase 8 promoter and functions as a transcriptional coactivator. |
| 393 | 23255602 | To confirm the biological significance of caspase 8 up-regulation, we tested tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)-mediated cell death assay in breast cancer cells. |
| 394 | 23255602 | Smad7 in apoptosis-resistant MCF7 cells markedly sensitized the cells to TRAIL-induced cell death by restoring the caspase cascade. |
| 395 | 23255602 | In conclusion, we suggest a novel role for Smad7 as a transcriptional coactivator for caspase 8 through the interaction with IRF1 in regulation of the cell death pathway. |
| 396 | 23255602 | Smad7 protein induces interferon regulatory factor 1-dependent transcriptional activation of caspase 8 to restore tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis. |
| 397 | 23255602 | Smad7 has been known as a negative regulator for the transforming growth factor-β (TGF-β) signaling pathway through feedback regulation. |
| 398 | 23255602 | By screening differentially regulated genes, we found that the caspase 8 gene was highly up-regulated in Smad7-expressing cells. |
| 399 | 23255602 | Smad7 was able to activate the caspase 8 promoter through recruitment of the interferon regulatory factor 1 (IRF1) transcription factor to the interferon-stimulated response element (ISRE) site. |
| 400 | 23255602 | Interaction of Smad7 on the caspase 8 promoter was confirmed with electrophoretic mobility shift assay and chromatin immunoprecipitation experiment. |
| 401 | 23255602 | Interestingly, Smad7 did not directly interact with the ISRE site, but it increased the binding activity of IRF1 with ISRE. |
| 402 | 23255602 | These results support that Smad7 recruits IRF1 protein on the caspase 8 promoter and functions as a transcriptional coactivator. |
| 403 | 23255602 | To confirm the biological significance of caspase 8 up-regulation, we tested tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)-mediated cell death assay in breast cancer cells. |
| 404 | 23255602 | Smad7 in apoptosis-resistant MCF7 cells markedly sensitized the cells to TRAIL-induced cell death by restoring the caspase cascade. |
| 405 | 23255602 | In conclusion, we suggest a novel role for Smad7 as a transcriptional coactivator for caspase 8 through the interaction with IRF1 in regulation of the cell death pathway. |
| 406 | 23255602 | Smad7 protein induces interferon regulatory factor 1-dependent transcriptional activation of caspase 8 to restore tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis. |
| 407 | 23255602 | Smad7 has been known as a negative regulator for the transforming growth factor-β (TGF-β) signaling pathway through feedback regulation. |
| 408 | 23255602 | By screening differentially regulated genes, we found that the caspase 8 gene was highly up-regulated in Smad7-expressing cells. |
| 409 | 23255602 | Smad7 was able to activate the caspase 8 promoter through recruitment of the interferon regulatory factor 1 (IRF1) transcription factor to the interferon-stimulated response element (ISRE) site. |
| 410 | 23255602 | Interaction of Smad7 on the caspase 8 promoter was confirmed with electrophoretic mobility shift assay and chromatin immunoprecipitation experiment. |
| 411 | 23255602 | Interestingly, Smad7 did not directly interact with the ISRE site, but it increased the binding activity of IRF1 with ISRE. |
| 412 | 23255602 | These results support that Smad7 recruits IRF1 protein on the caspase 8 promoter and functions as a transcriptional coactivator. |
| 413 | 23255602 | To confirm the biological significance of caspase 8 up-regulation, we tested tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)-mediated cell death assay in breast cancer cells. |
| 414 | 23255602 | Smad7 in apoptosis-resistant MCF7 cells markedly sensitized the cells to TRAIL-induced cell death by restoring the caspase cascade. |
| 415 | 23255602 | In conclusion, we suggest a novel role for Smad7 as a transcriptional coactivator for caspase 8 through the interaction with IRF1 in regulation of the cell death pathway. |
| 416 | 23255602 | Smad7 protein induces interferon regulatory factor 1-dependent transcriptional activation of caspase 8 to restore tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis. |
| 417 | 23255602 | Smad7 has been known as a negative regulator for the transforming growth factor-β (TGF-β) signaling pathway through feedback regulation. |
| 418 | 23255602 | By screening differentially regulated genes, we found that the caspase 8 gene was highly up-regulated in Smad7-expressing cells. |
| 419 | 23255602 | Smad7 was able to activate the caspase 8 promoter through recruitment of the interferon regulatory factor 1 (IRF1) transcription factor to the interferon-stimulated response element (ISRE) site. |
| 420 | 23255602 | Interaction of Smad7 on the caspase 8 promoter was confirmed with electrophoretic mobility shift assay and chromatin immunoprecipitation experiment. |
| 421 | 23255602 | Interestingly, Smad7 did not directly interact with the ISRE site, but it increased the binding activity of IRF1 with ISRE. |
| 422 | 23255602 | These results support that Smad7 recruits IRF1 protein on the caspase 8 promoter and functions as a transcriptional coactivator. |
| 423 | 23255602 | To confirm the biological significance of caspase 8 up-regulation, we tested tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)-mediated cell death assay in breast cancer cells. |
| 424 | 23255602 | Smad7 in apoptosis-resistant MCF7 cells markedly sensitized the cells to TRAIL-induced cell death by restoring the caspase cascade. |
| 425 | 23255602 | In conclusion, we suggest a novel role for Smad7 as a transcriptional coactivator for caspase 8 through the interaction with IRF1 in regulation of the cell death pathway. |
| 426 | 23255602 | Smad7 protein induces interferon regulatory factor 1-dependent transcriptional activation of caspase 8 to restore tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis. |
| 427 | 23255602 | Smad7 has been known as a negative regulator for the transforming growth factor-β (TGF-β) signaling pathway through feedback regulation. |
| 428 | 23255602 | By screening differentially regulated genes, we found that the caspase 8 gene was highly up-regulated in Smad7-expressing cells. |
| 429 | 23255602 | Smad7 was able to activate the caspase 8 promoter through recruitment of the interferon regulatory factor 1 (IRF1) transcription factor to the interferon-stimulated response element (ISRE) site. |
| 430 | 23255602 | Interaction of Smad7 on the caspase 8 promoter was confirmed with electrophoretic mobility shift assay and chromatin immunoprecipitation experiment. |
| 431 | 23255602 | Interestingly, Smad7 did not directly interact with the ISRE site, but it increased the binding activity of IRF1 with ISRE. |
| 432 | 23255602 | These results support that Smad7 recruits IRF1 protein on the caspase 8 promoter and functions as a transcriptional coactivator. |
| 433 | 23255602 | To confirm the biological significance of caspase 8 up-regulation, we tested tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)-mediated cell death assay in breast cancer cells. |
| 434 | 23255602 | Smad7 in apoptosis-resistant MCF7 cells markedly sensitized the cells to TRAIL-induced cell death by restoring the caspase cascade. |
| 435 | 23255602 | In conclusion, we suggest a novel role for Smad7 as a transcriptional coactivator for caspase 8 through the interaction with IRF1 in regulation of the cell death pathway. |
| 436 | 23267840 | All these events lead to excitotoxic neuronal death in the cerebral cortex, which was confirmed by the increased expression of caspase 3, caspase 8 and BCL2-associated X protein. |
| 437 | 23474487 | In addition, proapoptotic (FasL, Bid, and activation of caspase-8 and caspase-3) and survival signaling pathways (BclxL) were examined. |
| 438 | 23499715 | Deletion of Fgf21 gene does not affect testicular cell proliferation, but significantly increases the spontaneous incidence of testicular TUNEL positive cells with increases in the Bax/Bcl2 expression ratio and apoptosis-inducing factor (AIF) expression. |
| 439 | 23499715 | Diabetes induced significant increases in testicular TUNEL positive cells, Bax/Bcl2 expression ratio, AIF expression, CHOP and cleaved caspase-12 expression, and oxidative damage, but did not change the expression of cleaved caspase-3 and caspase-8. |
| 440 | 23499715 | Deletion of Fgf21 gene also significantly enhances diabetes-induced TUNEL positive cells along with the increased expression of Bax/Bcl2 ratio, AIF, CHOP, cleaved caspase-12, and oxidative damage, which was significantly prevented by the supplementation of exogenous FGF21. |
| 441 | 23566555 | Regulation of oxidative stress and somatostatin, cholecystokinin, apelin gene expressions by ghrelin in stomach of newborn diabetic rats. |
| 442 | 23566555 | The gene expressions of: somatostatin, cholecystokinin, apelin and the altered active caspase-3, active caspase-8, proliferating cell nuclear antigen, were investigated in the pyloric region of the stomach and antioxidant parameters were measured in all the stomach. |
| 443 | 23566555 | Exogenous ghrelin caused an increased activities of stomach catalase, superoxide dismutase, glutathione reductase and glutathione peroxidase in diabetic rats. |
| 444 | 23566555 | Numbers of somatostatin, cholecystokinin and proliferating cell nuclear antigen immunoreactive cells decreased in the diabetic+ghrelin group compared to the diabetic group. |
| 445 | 23566555 | Apelin mRNA expressions were remarkably less in the diabetic+ghrelin rats than in diabetic rats. |
| 446 | 23670348 | Pancreatic β-cell apoptotic numbers and the expression of caspase-8, -9, -3 in islet increased in diabetic mice, which was reversed by elevated adiponectin in plenti-acdc-EGFP-treated mice. |
| 447 | 23689355 | Caspase-1 is a member of the intracellular cysteine protease family that mediates inflammation through the activation of the cytokines interleukin-1β (IL-1β) and interleukin-18 (IL-18). |
| 448 | 23689355 | As mice lacking IL-18 become obese and insulin resistant, and both IL-18 and IL-1β have a role in overall energy balance, we sought to determine whether caspase-1 deficiency also causes obesity. |
| 449 | 23689355 | Caspase-1-/- mice maintained lower but detectable levels of IL-18 compared with WT mice. |
| 450 | 23689355 | Overall, this study suggests that the lower level of IL-18 in caspase-1-/- mice might be causing obesity development similarly to IL-18-deficient mice. |
| 451 | 23982205 | Maternal hyperglycemia activates an ASK1-FoxO3a-caspase 8 pathway that leads to embryonic neural tube defects. |
| 452 | 23982205 | ASK1 activation stimulated the activity of the transcription factor FoxO3a, which increased the abundance of the apoptosis-promoting adaptor protein TRADD, leading to activation of caspase 8. |
| 453 | 23982205 | Hyperglycemia-induced apoptosis and the development of neural tube defects were reduced with genetic ablation of either FoxO3a or Casp8 or inhibition of ASK1 by thioredoxin. |
| 454 | 23982205 | Examination of human neural tissues affected by neural tube defects revealed increased activation or abundance of ASK1, FoxO3a, TRADD, and caspase 8. |
| 455 | 23982205 | Thus, activation of an ASK1-FoxO3a-TRADD-caspase 8 pathway participates in the development of neural tube defects, which could be prevented by inhibiting intermediates in this cascade. |
| 456 | 23982205 | Maternal hyperglycemia activates an ASK1-FoxO3a-caspase 8 pathway that leads to embryonic neural tube defects. |
| 457 | 23982205 | ASK1 activation stimulated the activity of the transcription factor FoxO3a, which increased the abundance of the apoptosis-promoting adaptor protein TRADD, leading to activation of caspase 8. |
| 458 | 23982205 | Hyperglycemia-induced apoptosis and the development of neural tube defects were reduced with genetic ablation of either FoxO3a or Casp8 or inhibition of ASK1 by thioredoxin. |
| 459 | 23982205 | Examination of human neural tissues affected by neural tube defects revealed increased activation or abundance of ASK1, FoxO3a, TRADD, and caspase 8. |
| 460 | 23982205 | Thus, activation of an ASK1-FoxO3a-TRADD-caspase 8 pathway participates in the development of neural tube defects, which could be prevented by inhibiting intermediates in this cascade. |
| 461 | 23982205 | Maternal hyperglycemia activates an ASK1-FoxO3a-caspase 8 pathway that leads to embryonic neural tube defects. |
| 462 | 23982205 | ASK1 activation stimulated the activity of the transcription factor FoxO3a, which increased the abundance of the apoptosis-promoting adaptor protein TRADD, leading to activation of caspase 8. |
| 463 | 23982205 | Hyperglycemia-induced apoptosis and the development of neural tube defects were reduced with genetic ablation of either FoxO3a or Casp8 or inhibition of ASK1 by thioredoxin. |
| 464 | 23982205 | Examination of human neural tissues affected by neural tube defects revealed increased activation or abundance of ASK1, FoxO3a, TRADD, and caspase 8. |
| 465 | 23982205 | Thus, activation of an ASK1-FoxO3a-TRADD-caspase 8 pathway participates in the development of neural tube defects, which could be prevented by inhibiting intermediates in this cascade. |
| 466 | 23982205 | Maternal hyperglycemia activates an ASK1-FoxO3a-caspase 8 pathway that leads to embryonic neural tube defects. |
| 467 | 23982205 | ASK1 activation stimulated the activity of the transcription factor FoxO3a, which increased the abundance of the apoptosis-promoting adaptor protein TRADD, leading to activation of caspase 8. |
| 468 | 23982205 | Hyperglycemia-induced apoptosis and the development of neural tube defects were reduced with genetic ablation of either FoxO3a or Casp8 or inhibition of ASK1 by thioredoxin. |
| 469 | 23982205 | Examination of human neural tissues affected by neural tube defects revealed increased activation or abundance of ASK1, FoxO3a, TRADD, and caspase 8. |
| 470 | 23982205 | Thus, activation of an ASK1-FoxO3a-TRADD-caspase 8 pathway participates in the development of neural tube defects, which could be prevented by inhibiting intermediates in this cascade. |
| 471 | 23982205 | Maternal hyperglycemia activates an ASK1-FoxO3a-caspase 8 pathway that leads to embryonic neural tube defects. |
| 472 | 23982205 | ASK1 activation stimulated the activity of the transcription factor FoxO3a, which increased the abundance of the apoptosis-promoting adaptor protein TRADD, leading to activation of caspase 8. |
| 473 | 23982205 | Hyperglycemia-induced apoptosis and the development of neural tube defects were reduced with genetic ablation of either FoxO3a or Casp8 or inhibition of ASK1 by thioredoxin. |
| 474 | 23982205 | Examination of human neural tissues affected by neural tube defects revealed increased activation or abundance of ASK1, FoxO3a, TRADD, and caspase 8. |
| 475 | 23982205 | Thus, activation of an ASK1-FoxO3a-TRADD-caspase 8 pathway participates in the development of neural tube defects, which could be prevented by inhibiting intermediates in this cascade. |
| 476 | 24001238 | Furthermore, the Fas/Fas-associated protein with death domain pathway-induced caspase 8-mediated apoptosis that was observed in the cardiomyocytes of the STZ-induced DM rats was also found to be controlled in the probiotic-treated rats. |