Ignet

Gene Information

Gene symbol: CYP3A

Gene name: cytochrome P450, family 3, subfamily A

HGNC ID: 2635

Related Genes

#	Gene Symbol	Number of hits
1	CCL4	1 hits
2	CRYGEP1	1 hits
3	CYP1A1	1 hits
4	CYP2B	1 hits
5	CYP2B6	1 hits
6	CYP2C19	1 hits
7	CYP2D7P1	1 hits
8	CYP2E1	1 hits
9	CYP3A4	1 hits
10	CYP3A5	1 hits
11	FMO1	1 hits
12	HNF4A	1 hits
13	INS	1 hits
14	NR1I2	1 hits
15	TBXAS1	1 hits
16	TRO	1 hits

Related Sentences

#	PMID	Sentence
1	9402951	Insulin effects on CYP2E1, 2B, 3A, and 4A expression in primary cultured rat hepatocytes.
2	9402951	Although hyperketonemia and/or altered growth hormone secretion caused by diabetes have been implicated in enhanced CYP2E1, 2B, 3A and 4A expression, the effect of insulin on hepatic P450 expression, in the absence of associated metabolic/hormonal alterations, remains unknown.
3	9402951	Dispos., 23:681, 1995) to express stable and inducible CYP2E1 mRNA and protein levels, and provide an excellent system for mechanistic examination of the effect of insulin on CYP2E1, 2B, 3A and 4A expression.
4	9402951	Maintaining primary rat hepatocytes in culture in the absence of insulin for 48, 72, or 96 h increased CYP2E1 mRNA levels 5-, 11-, and 4-fold, respectively, relative to cells maintained in the presence of the standard concentration of 1 microM insulin.
5	9402951	In contrast, CYP2B mRNA levels increased only approximately 2-fold in the absence of insulin, when compared with the presence of 1 microM insulin.
6	9402951	CYP2E1 and 2B protein levels were increased 6.7- and 3.8-fold, respectively, in cells cultured for 96 h in the absence of insulin as compared with those cultured in medium containing 1 microM insulin.
7	9402951	Concentration-response studies revealed that decreasing the concentration of insulin below 10 nM (i.e. 1 nM, 0.1 nM, no insulin) increased CYP2E1 mRNA levels 4-, 7-, and 11-fold, respectively.
8	9402951	As CYP3A and 4A expression is also elevated in diabetic rats, the effects of insulin on these P450s was also examined.
9	9402951	CYP3A mRNA levels were unaltered and CYP4A mRNA levels were decreased marginally (approximately 50%) by the absence of insulin relative to levels in cells cultured in the presence of 1 microM insulin over 96 h in culture.
10	9402951	The results of this study provide evidence that insulin itself, in the absence of other diabetes-induced metabolic or hormonal alterations, affects CYP2E1 and 2B, but not CYP3A or 4A, expression in primary cultured rat hepatocytes.
11	9402951	Furthermore, CYP2E1 expression is differentially regulated by insulin relative to CYP2B, 3A or 4A.
12	9402951	This study also demonstrates that decreasing the concentration of insulin in the culture medium provides a method by which CYP2E1 levels can be increased in primary cultured hepatocytes to facilitate mechanistic studies on the regulation of CYP2E1 expression.
13	9402951	Insulin effects on CYP2E1, 2B, 3A, and 4A expression in primary cultured rat hepatocytes.
14	9402951	Although hyperketonemia and/or altered growth hormone secretion caused by diabetes have been implicated in enhanced CYP2E1, 2B, 3A and 4A expression, the effect of insulin on hepatic P450 expression, in the absence of associated metabolic/hormonal alterations, remains unknown.
15	9402951	Dispos., 23:681, 1995) to express stable and inducible CYP2E1 mRNA and protein levels, and provide an excellent system for mechanistic examination of the effect of insulin on CYP2E1, 2B, 3A and 4A expression.
16	9402951	Maintaining primary rat hepatocytes in culture in the absence of insulin for 48, 72, or 96 h increased CYP2E1 mRNA levels 5-, 11-, and 4-fold, respectively, relative to cells maintained in the presence of the standard concentration of 1 microM insulin.
17	9402951	In contrast, CYP2B mRNA levels increased only approximately 2-fold in the absence of insulin, when compared with the presence of 1 microM insulin.
18	9402951	CYP2E1 and 2B protein levels were increased 6.7- and 3.8-fold, respectively, in cells cultured for 96 h in the absence of insulin as compared with those cultured in medium containing 1 microM insulin.
19	9402951	Concentration-response studies revealed that decreasing the concentration of insulin below 10 nM (i.e. 1 nM, 0.1 nM, no insulin) increased CYP2E1 mRNA levels 4-, 7-, and 11-fold, respectively.
20	9402951	As CYP3A and 4A expression is also elevated in diabetic rats, the effects of insulin on these P450s was also examined.
21	9402951	CYP3A mRNA levels were unaltered and CYP4A mRNA levels were decreased marginally (approximately 50%) by the absence of insulin relative to levels in cells cultured in the presence of 1 microM insulin over 96 h in culture.
22	9402951	The results of this study provide evidence that insulin itself, in the absence of other diabetes-induced metabolic or hormonal alterations, affects CYP2E1 and 2B, but not CYP3A or 4A, expression in primary cultured rat hepatocytes.
23	9402951	Furthermore, CYP2E1 expression is differentially regulated by insulin relative to CYP2B, 3A or 4A.
24	9402951	This study also demonstrates that decreasing the concentration of insulin in the culture medium provides a method by which CYP2E1 levels can be increased in primary cultured hepatocytes to facilitate mechanistic studies on the regulation of CYP2E1 expression.
25	9402951	Insulin effects on CYP2E1, 2B, 3A, and 4A expression in primary cultured rat hepatocytes.
26	9402951	Although hyperketonemia and/or altered growth hormone secretion caused by diabetes have been implicated in enhanced CYP2E1, 2B, 3A and 4A expression, the effect of insulin on hepatic P450 expression, in the absence of associated metabolic/hormonal alterations, remains unknown.
27	9402951	Dispos., 23:681, 1995) to express stable and inducible CYP2E1 mRNA and protein levels, and provide an excellent system for mechanistic examination of the effect of insulin on CYP2E1, 2B, 3A and 4A expression.
28	9402951	Maintaining primary rat hepatocytes in culture in the absence of insulin for 48, 72, or 96 h increased CYP2E1 mRNA levels 5-, 11-, and 4-fold, respectively, relative to cells maintained in the presence of the standard concentration of 1 microM insulin.
29	9402951	In contrast, CYP2B mRNA levels increased only approximately 2-fold in the absence of insulin, when compared with the presence of 1 microM insulin.
30	9402951	CYP2E1 and 2B protein levels were increased 6.7- and 3.8-fold, respectively, in cells cultured for 96 h in the absence of insulin as compared with those cultured in medium containing 1 microM insulin.
31	9402951	Concentration-response studies revealed that decreasing the concentration of insulin below 10 nM (i.e. 1 nM, 0.1 nM, no insulin) increased CYP2E1 mRNA levels 4-, 7-, and 11-fold, respectively.
32	9402951	As CYP3A and 4A expression is also elevated in diabetic rats, the effects of insulin on these P450s was also examined.
33	9402951	CYP3A mRNA levels were unaltered and CYP4A mRNA levels were decreased marginally (approximately 50%) by the absence of insulin relative to levels in cells cultured in the presence of 1 microM insulin over 96 h in culture.
34	9402951	The results of this study provide evidence that insulin itself, in the absence of other diabetes-induced metabolic or hormonal alterations, affects CYP2E1 and 2B, but not CYP3A or 4A, expression in primary cultured rat hepatocytes.
35	9402951	Furthermore, CYP2E1 expression is differentially regulated by insulin relative to CYP2B, 3A or 4A.
36	9402951	This study also demonstrates that decreasing the concentration of insulin in the culture medium provides a method by which CYP2E1 levels can be increased in primary cultured hepatocytes to facilitate mechanistic studies on the regulation of CYP2E1 expression.
37	10215695	Insulin differentially affects xenobiotic-enhanced, cytochrome P-450 (CYP)2E1, CYP2B, CYP3A, and CYP4A expression in primary cultured rat hepatocytes.
38	10215695	Uncontrolled diabetes results in enhanced expression of cytochrome P-450 (CYP)2E1, CYP2B, CYP3A, and CYP4A.
39	10215695	Because of the simultaneous and confounding metabolic and hormonal changes that occur in vivo as a consequence of diabetes, primary cultured rat hepatocytes provide an excellent model system for examination of the effects of insulin on P-450 expression and on xenobiotic-mediated P-450 expression.
40	10215695	In the present study, we examined the effects of insulin on pyridine-, phenobarbital-, and ciprofibrate-mediated expression of CYP2E1, CYP2B, CYP3A, and CYP4A in primary cultured rat hepatocytes.
41	10215695	Pyridine addition to primary rat hepatocytes cultured in the presence of 1 nM insulin or in the absence of insulin resulted in a 3.5-fold and 3-fold enhancement in CYP2E1 protein expression, respectively, in the absence of any pyridine-mediated increase in mRNA expression.
42	10215695	Thus, the fold-induction of CYP2E1 protein in response to pyridine was 1.5- to 1.8-fold greater in either the absence of insulin or in the presence of 1 nM insulin, respectively, than that monitored in the presence of 1 microM insulin.
43	10215695	To examine whether insulin effects on xenobiotic-mediated CYP2E1 expression were selective, insulin effects on xenobiotic-mediated expression of transcriptionally regulated CYP2B, CYP3A, and CYP4A were examined.
44	10215695	Pyridine- or phenobarbital-mediated induction of CYP2B mRNA and protein expression in hepatocytes was suppressed by as much as 80% at lower insulin levels (0 and 1 nM), relative to the level monitored in the presence of 1 microM insulin.
45	10215695	Omitting insulin from the medium resulted in a 50% decrease in CYP3A mRNA levels in response to phenobarbital treatment and a 30% decrease in CYP4A mRNA levels in response to ciprofibrate treatment, relative to the level obtained in response to these treatments in the presence of 1 microM insulin.
46	10215695	The results of this study demonstrate that decreasing the insulin level in the primary hepatocyte culture medium enhanced xenobiotic-mediated CYP2E1 expression, whereas lower insulin levels suppressed xenobiotic-mediated CYP2B, CYP3A, and CYP4A expression in this cell culture system.
47	10215695	Insulin differentially affects xenobiotic-enhanced, cytochrome P-450 (CYP)2E1, CYP2B, CYP3A, and CYP4A expression in primary cultured rat hepatocytes.
48	10215695	Uncontrolled diabetes results in enhanced expression of cytochrome P-450 (CYP)2E1, CYP2B, CYP3A, and CYP4A.
49	10215695	Because of the simultaneous and confounding metabolic and hormonal changes that occur in vivo as a consequence of diabetes, primary cultured rat hepatocytes provide an excellent model system for examination of the effects of insulin on P-450 expression and on xenobiotic-mediated P-450 expression.
50	10215695	In the present study, we examined the effects of insulin on pyridine-, phenobarbital-, and ciprofibrate-mediated expression of CYP2E1, CYP2B, CYP3A, and CYP4A in primary cultured rat hepatocytes.
51	10215695	Pyridine addition to primary rat hepatocytes cultured in the presence of 1 nM insulin or in the absence of insulin resulted in a 3.5-fold and 3-fold enhancement in CYP2E1 protein expression, respectively, in the absence of any pyridine-mediated increase in mRNA expression.
52	10215695	Thus, the fold-induction of CYP2E1 protein in response to pyridine was 1.5- to 1.8-fold greater in either the absence of insulin or in the presence of 1 nM insulin, respectively, than that monitored in the presence of 1 microM insulin.
53	10215695	To examine whether insulin effects on xenobiotic-mediated CYP2E1 expression were selective, insulin effects on xenobiotic-mediated expression of transcriptionally regulated CYP2B, CYP3A, and CYP4A were examined.
54	10215695	Pyridine- or phenobarbital-mediated induction of CYP2B mRNA and protein expression in hepatocytes was suppressed by as much as 80% at lower insulin levels (0 and 1 nM), relative to the level monitored in the presence of 1 microM insulin.
55	10215695	Omitting insulin from the medium resulted in a 50% decrease in CYP3A mRNA levels in response to phenobarbital treatment and a 30% decrease in CYP4A mRNA levels in response to ciprofibrate treatment, relative to the level obtained in response to these treatments in the presence of 1 microM insulin.
56	10215695	The results of this study demonstrate that decreasing the insulin level in the primary hepatocyte culture medium enhanced xenobiotic-mediated CYP2E1 expression, whereas lower insulin levels suppressed xenobiotic-mediated CYP2B, CYP3A, and CYP4A expression in this cell culture system.
57	10215695	Insulin differentially affects xenobiotic-enhanced, cytochrome P-450 (CYP)2E1, CYP2B, CYP3A, and CYP4A expression in primary cultured rat hepatocytes.
58	10215695	Uncontrolled diabetes results in enhanced expression of cytochrome P-450 (CYP)2E1, CYP2B, CYP3A, and CYP4A.
59	10215695	Because of the simultaneous and confounding metabolic and hormonal changes that occur in vivo as a consequence of diabetes, primary cultured rat hepatocytes provide an excellent model system for examination of the effects of insulin on P-450 expression and on xenobiotic-mediated P-450 expression.
60	10215695	In the present study, we examined the effects of insulin on pyridine-, phenobarbital-, and ciprofibrate-mediated expression of CYP2E1, CYP2B, CYP3A, and CYP4A in primary cultured rat hepatocytes.
61	10215695	Pyridine addition to primary rat hepatocytes cultured in the presence of 1 nM insulin or in the absence of insulin resulted in a 3.5-fold and 3-fold enhancement in CYP2E1 protein expression, respectively, in the absence of any pyridine-mediated increase in mRNA expression.
62	10215695	Thus, the fold-induction of CYP2E1 protein in response to pyridine was 1.5- to 1.8-fold greater in either the absence of insulin or in the presence of 1 nM insulin, respectively, than that monitored in the presence of 1 microM insulin.
63	10215695	To examine whether insulin effects on xenobiotic-mediated CYP2E1 expression were selective, insulin effects on xenobiotic-mediated expression of transcriptionally regulated CYP2B, CYP3A, and CYP4A were examined.
64	10215695	Pyridine- or phenobarbital-mediated induction of CYP2B mRNA and protein expression in hepatocytes was suppressed by as much as 80% at lower insulin levels (0 and 1 nM), relative to the level monitored in the presence of 1 microM insulin.
65	10215695	Omitting insulin from the medium resulted in a 50% decrease in CYP3A mRNA levels in response to phenobarbital treatment and a 30% decrease in CYP4A mRNA levels in response to ciprofibrate treatment, relative to the level obtained in response to these treatments in the presence of 1 microM insulin.
66	10215695	The results of this study demonstrate that decreasing the insulin level in the primary hepatocyte culture medium enhanced xenobiotic-mediated CYP2E1 expression, whereas lower insulin levels suppressed xenobiotic-mediated CYP2B, CYP3A, and CYP4A expression in this cell culture system.
67	10215695	Insulin differentially affects xenobiotic-enhanced, cytochrome P-450 (CYP)2E1, CYP2B, CYP3A, and CYP4A expression in primary cultured rat hepatocytes.
68	10215695	Uncontrolled diabetes results in enhanced expression of cytochrome P-450 (CYP)2E1, CYP2B, CYP3A, and CYP4A.
69	10215695	Because of the simultaneous and confounding metabolic and hormonal changes that occur in vivo as a consequence of diabetes, primary cultured rat hepatocytes provide an excellent model system for examination of the effects of insulin on P-450 expression and on xenobiotic-mediated P-450 expression.
70	10215695	In the present study, we examined the effects of insulin on pyridine-, phenobarbital-, and ciprofibrate-mediated expression of CYP2E1, CYP2B, CYP3A, and CYP4A in primary cultured rat hepatocytes.
71	10215695	Pyridine addition to primary rat hepatocytes cultured in the presence of 1 nM insulin or in the absence of insulin resulted in a 3.5-fold and 3-fold enhancement in CYP2E1 protein expression, respectively, in the absence of any pyridine-mediated increase in mRNA expression.
72	10215695	Thus, the fold-induction of CYP2E1 protein in response to pyridine was 1.5- to 1.8-fold greater in either the absence of insulin or in the presence of 1 nM insulin, respectively, than that monitored in the presence of 1 microM insulin.
73	10215695	To examine whether insulin effects on xenobiotic-mediated CYP2E1 expression were selective, insulin effects on xenobiotic-mediated expression of transcriptionally regulated CYP2B, CYP3A, and CYP4A were examined.
74	10215695	Pyridine- or phenobarbital-mediated induction of CYP2B mRNA and protein expression in hepatocytes was suppressed by as much as 80% at lower insulin levels (0 and 1 nM), relative to the level monitored in the presence of 1 microM insulin.
75	10215695	Omitting insulin from the medium resulted in a 50% decrease in CYP3A mRNA levels in response to phenobarbital treatment and a 30% decrease in CYP4A mRNA levels in response to ciprofibrate treatment, relative to the level obtained in response to these treatments in the presence of 1 microM insulin.
76	10215695	The results of this study demonstrate that decreasing the insulin level in the primary hepatocyte culture medium enhanced xenobiotic-mediated CYP2E1 expression, whereas lower insulin levels suppressed xenobiotic-mediated CYP2B, CYP3A, and CYP4A expression in this cell culture system.
77	10215695	Insulin differentially affects xenobiotic-enhanced, cytochrome P-450 (CYP)2E1, CYP2B, CYP3A, and CYP4A expression in primary cultured rat hepatocytes.
78	10215695	Uncontrolled diabetes results in enhanced expression of cytochrome P-450 (CYP)2E1, CYP2B, CYP3A, and CYP4A.
79	10215695	Because of the simultaneous and confounding metabolic and hormonal changes that occur in vivo as a consequence of diabetes, primary cultured rat hepatocytes provide an excellent model system for examination of the effects of insulin on P-450 expression and on xenobiotic-mediated P-450 expression.
80	10215695	In the present study, we examined the effects of insulin on pyridine-, phenobarbital-, and ciprofibrate-mediated expression of CYP2E1, CYP2B, CYP3A, and CYP4A in primary cultured rat hepatocytes.
81	10215695	Pyridine addition to primary rat hepatocytes cultured in the presence of 1 nM insulin or in the absence of insulin resulted in a 3.5-fold and 3-fold enhancement in CYP2E1 protein expression, respectively, in the absence of any pyridine-mediated increase in mRNA expression.
82	10215695	Thus, the fold-induction of CYP2E1 protein in response to pyridine was 1.5- to 1.8-fold greater in either the absence of insulin or in the presence of 1 nM insulin, respectively, than that monitored in the presence of 1 microM insulin.
83	10215695	To examine whether insulin effects on xenobiotic-mediated CYP2E1 expression were selective, insulin effects on xenobiotic-mediated expression of transcriptionally regulated CYP2B, CYP3A, and CYP4A were examined.
84	10215695	Pyridine- or phenobarbital-mediated induction of CYP2B mRNA and protein expression in hepatocytes was suppressed by as much as 80% at lower insulin levels (0 and 1 nM), relative to the level monitored in the presence of 1 microM insulin.
85	10215695	Omitting insulin from the medium resulted in a 50% decrease in CYP3A mRNA levels in response to phenobarbital treatment and a 30% decrease in CYP4A mRNA levels in response to ciprofibrate treatment, relative to the level obtained in response to these treatments in the presence of 1 microM insulin.
86	10215695	The results of this study demonstrate that decreasing the insulin level in the primary hepatocyte culture medium enhanced xenobiotic-mediated CYP2E1 expression, whereas lower insulin levels suppressed xenobiotic-mediated CYP2B, CYP3A, and CYP4A expression in this cell culture system.
87	10215695	Insulin differentially affects xenobiotic-enhanced, cytochrome P-450 (CYP)2E1, CYP2B, CYP3A, and CYP4A expression in primary cultured rat hepatocytes.
88	10215695	Uncontrolled diabetes results in enhanced expression of cytochrome P-450 (CYP)2E1, CYP2B, CYP3A, and CYP4A.
89	10215695	Because of the simultaneous and confounding metabolic and hormonal changes that occur in vivo as a consequence of diabetes, primary cultured rat hepatocytes provide an excellent model system for examination of the effects of insulin on P-450 expression and on xenobiotic-mediated P-450 expression.
90	10215695	In the present study, we examined the effects of insulin on pyridine-, phenobarbital-, and ciprofibrate-mediated expression of CYP2E1, CYP2B, CYP3A, and CYP4A in primary cultured rat hepatocytes.
91	10215695	Pyridine addition to primary rat hepatocytes cultured in the presence of 1 nM insulin or in the absence of insulin resulted in a 3.5-fold and 3-fold enhancement in CYP2E1 protein expression, respectively, in the absence of any pyridine-mediated increase in mRNA expression.
92	10215695	Thus, the fold-induction of CYP2E1 protein in response to pyridine was 1.5- to 1.8-fold greater in either the absence of insulin or in the presence of 1 nM insulin, respectively, than that monitored in the presence of 1 microM insulin.
93	10215695	To examine whether insulin effects on xenobiotic-mediated CYP2E1 expression were selective, insulin effects on xenobiotic-mediated expression of transcriptionally regulated CYP2B, CYP3A, and CYP4A were examined.
94	10215695	Pyridine- or phenobarbital-mediated induction of CYP2B mRNA and protein expression in hepatocytes was suppressed by as much as 80% at lower insulin levels (0 and 1 nM), relative to the level monitored in the presence of 1 microM insulin.
95	10215695	Omitting insulin from the medium resulted in a 50% decrease in CYP3A mRNA levels in response to phenobarbital treatment and a 30% decrease in CYP4A mRNA levels in response to ciprofibrate treatment, relative to the level obtained in response to these treatments in the presence of 1 microM insulin.
96	10215695	The results of this study demonstrate that decreasing the insulin level in the primary hepatocyte culture medium enhanced xenobiotic-mediated CYP2E1 expression, whereas lower insulin levels suppressed xenobiotic-mediated CYP2B, CYP3A, and CYP4A expression in this cell culture system.
97	10497147	Troglitazone increases cytochrome P-450 3A protein and activity in primary cultures of human hepatocytes.
98	10497147	TRO is known to increase the activity of cytochrome P-450 (CYP) 3A in vivo.
99	10497147	We have investigated the effect of TRO on CYP3A protein content and the activity of CYP3A (as measured by the formation of 6beta-hydroxytestosterone formation) in primary cultures of human hepatocytes in comparison with rifampicin (RIF).
100	11826398	Insulin signaling in the transcriptional and posttranscriptional regulation of CYP2E1 expression.
101	11826398	Diabetes has been reported to increase the expression of cytochrome P450 (CYP) 2E1 messenger RNA (mRNA) and protein several-fold, and enhanced expression has been associated with elevated ketone bodies.
102	11826398	Primary cultured rat hepatocytes were used to explore ketone body and insulin regulation of CYP2E1 expression.
103	11826398	Insulin produced a concentration-dependent decrease in CYP2E1 mRNA levels, and insulin receptor immunoprecipitation showed a correspondence between receptor phosphorylation and the decrease in CYP2E1 mRNA levels at physiologic levels of insulin.
104	11826398	The phosphatidylinositol 3-kinase (PI3-kinase) inhibitors wortmannin or LY294002 and rapamycin, an inhibitor of p70 S6 kinase phosphorylation, ameliorated the insulin-mediated decrease in CYP2E1 mRNA levels.
105	11826398	Geldanamycin, which inhibits Src kinase, also abrogated the insulin-mediated decrease in CYP2E1 mRNA levels.
106	11826398	In contrast, the protein kinase C (PKC) inhibitor bisindolylmaleimide, the mitogen-activated protein kinase kinase (MEK) inhibitor PD98059, and the p38 mitogen-activated protein (MAP) kinase inhibitor SB202190 did not affect the insulin-mediated decrease in CYP2E1.
107	11826398	CYP2E1 mRNA half-life decreased from approximately 48 hours in the absence of insulin to approximately 15 hours at 10 nmol/L insulin, and this decrease was prevented by wortmannin.
108	11826398	The half-life of CYP2B mRNA was increased by insulin, whereas that of CYP3A was unaffected.
109	11826398	Analysis of CYP2E1 gene transcription using heterogeneous nuclear RNA (hnRNA) showed that insulin suppressed CYP2E1 transcription.
110	11826398	In conclusion, these data show involvement of transcriptional and posttranscriptional mechanisms in the insulin-mediated regulation of CYP2E1 and implicate PI3-kinase, p70 S6 kinase, and Src kinase in mediating these effects.
111	12062933	We studied the effects of TRZ on the hepatotoxicity of carbon tetrachloride (CCl(4)) and acetaminophen (APAP) in rats, both of which exert their toxic effects through bioactivation associated with cytochrome P450 3A (CYP3A) and 2E1 (CYP2E1).
112	12062933	Three weeks later, the rats were either sacrificed for an in vitro metabolism study or challenged with 0.50 g/kg CCl(4) p.o. or 0.75 g/kg APAP i.p.TRZ at 100 and 500 mg/kg/rat increased the CYP3A level as well as the testosterone 6beta-hydroxylation activities in liver microsomes, but did not affect CYP2E1.
113	12062933	TRZ also enhanced APAP hepatotoxicity, as evidenced by significantly increased levels of alanine aminotransferase, aspartate aminotransferase and alpha-glutathione S-transferase in the plasma of rats, and by significantly low hepatic glutathione concentration.
114	12062933	We studied the effects of TRZ on the hepatotoxicity of carbon tetrachloride (CCl(4)) and acetaminophen (APAP) in rats, both of which exert their toxic effects through bioactivation associated with cytochrome P450 3A (CYP3A) and 2E1 (CYP2E1).
115	12062933	Three weeks later, the rats were either sacrificed for an in vitro metabolism study or challenged with 0.50 g/kg CCl(4) p.o. or 0.75 g/kg APAP i.p.TRZ at 100 and 500 mg/kg/rat increased the CYP3A level as well as the testosterone 6beta-hydroxylation activities in liver microsomes, but did not affect CYP2E1.
116	12062933	TRZ also enhanced APAP hepatotoxicity, as evidenced by significantly increased levels of alanine aminotransferase, aspartate aminotransferase and alpha-glutathione S-transferase in the plasma of rats, and by significantly low hepatic glutathione concentration.
117	12569201	On activation by these compounds, PXR coordinately induces a network of transporters, cytochrome P450 enzymes, and other genes that effectively clear xenobiotics from the liver and intestine.
118	12569201	To address this issue, we noted that there is substantial overlap in the substrate specificities of PXR and its critical CYP3A target gene.
119	12569201	This prompted us to ask whether endogenous CYP3A substrates also serve as PXR ligands.
120	12569201	We demonstrate that 5beta-cholestane-3alpha,7alpha,12alpha-triol (triol), a cholesterol-derived CYP3A substrate, is a potent PXR agonist that effectively induces cyp3a expression in mice.
121	12569201	We now demonstrate that triol fails to activate human PXR or induce the CYP3A-salvage pathway.
122	12569201	This explains why humans are more susceptible to sterol accumulation and suggests that synthetic ligands for human PXR could be used to treat cerebrotendinous xanthomatosis and other disorders of cholesterol excess.
123	12569201	On activation by these compounds, PXR coordinately induces a network of transporters, cytochrome P450 enzymes, and other genes that effectively clear xenobiotics from the liver and intestine.
124	12569201	To address this issue, we noted that there is substantial overlap in the substrate specificities of PXR and its critical CYP3A target gene.
125	12569201	This prompted us to ask whether endogenous CYP3A substrates also serve as PXR ligands.
126	12569201	We demonstrate that 5beta-cholestane-3alpha,7alpha,12alpha-triol (triol), a cholesterol-derived CYP3A substrate, is a potent PXR agonist that effectively induces cyp3a expression in mice.
127	12569201	We now demonstrate that triol fails to activate human PXR or induce the CYP3A-salvage pathway.
128	12569201	This explains why humans are more susceptible to sterol accumulation and suggests that synthetic ligands for human PXR could be used to treat cerebrotendinous xanthomatosis and other disorders of cholesterol excess.
129	12569201	On activation by these compounds, PXR coordinately induces a network of transporters, cytochrome P450 enzymes, and other genes that effectively clear xenobiotics from the liver and intestine.
130	12569201	To address this issue, we noted that there is substantial overlap in the substrate specificities of PXR and its critical CYP3A target gene.
131	12569201	This prompted us to ask whether endogenous CYP3A substrates also serve as PXR ligands.
132	12569201	We demonstrate that 5beta-cholestane-3alpha,7alpha,12alpha-triol (triol), a cholesterol-derived CYP3A substrate, is a potent PXR agonist that effectively induces cyp3a expression in mice.
133	12569201	We now demonstrate that triol fails to activate human PXR or induce the CYP3A-salvage pathway.
134	12569201	This explains why humans are more susceptible to sterol accumulation and suggests that synthetic ligands for human PXR could be used to treat cerebrotendinous xanthomatosis and other disorders of cholesterol excess.
135	12569201	On activation by these compounds, PXR coordinately induces a network of transporters, cytochrome P450 enzymes, and other genes that effectively clear xenobiotics from the liver and intestine.
136	12569201	To address this issue, we noted that there is substantial overlap in the substrate specificities of PXR and its critical CYP3A target gene.
137	12569201	This prompted us to ask whether endogenous CYP3A substrates also serve as PXR ligands.
138	12569201	We demonstrate that 5beta-cholestane-3alpha,7alpha,12alpha-triol (triol), a cholesterol-derived CYP3A substrate, is a potent PXR agonist that effectively induces cyp3a expression in mice.
139	12569201	We now demonstrate that triol fails to activate human PXR or induce the CYP3A-salvage pathway.
140	12569201	This explains why humans are more susceptible to sterol accumulation and suggests that synthetic ligands for human PXR could be used to treat cerebrotendinous xanthomatosis and other disorders of cholesterol excess.
141	15150316	In this study, we identified the expression of cytochromes P450 in rat white adipose tissues and investigated the effects of typical lipophilic cytochrome P450 inducers, namely phenobarbital, dexamethasone, and beta-naphthoflavone.
142	15150316	Phenobarbital and dexamethasone also induced both the mRNA and protein of CYP2Bs and CYP3As, respectively, in adipose tissue, although significant interindividual differences were observed.
143	15150316	These results suggest that the mechanisms by which cytochrome P450 genes are regulated in the liver are also functional in rat adipose tissues.
144	16488120	Flavin-containing monooxygenase and cytochrome P450 activities in experimental diabetes.
145	16488120	Microsomal monooxygenases - cytochrome P450 (CYP, EC 1.14.14.1) and flavin-containing monooxygenase (FMO, EC 1.14.13.8) - have profound roles in drug metabolism.
146	16488120	While the induction of some metabolic enzymes such as hepatic FMO and intestinal CYP1A, CYP2B is recognized in experimental diabetes, the effect of insulin treatment on FMO and intestinal CYP3A in diabetic animals has not been reported before.
147	16488120	Hepatic FMO1 activity increased in diabetic rats, but it was restored to control value on insulin treatment.
148	16488120	Insulin itself had no effect on FMO1 activity in non-diabetic animals.
149	16488120	A remarkable increase of total CYP content was accompanied by a reduced CYP3A specific enzyme activity in the small intestine of diabetic animals.
150	16488120	Both, hepatic FMO1 and intestinal CYP3A activity correlated with average blood glucose concentration in untreated diabetic rats.
151	16488120	These results indicate that insulin is involved in the regulation of hepatic FMO1 and intestinal CYP3A in rats.
152	16488120	The marked reduction of intestinal CYP3A capacity suggests that diabetes exerts a substantial effect on the activity of most determining intestinal CYP enzyme.
153	16488120	Flavin-containing monooxygenase and cytochrome P450 activities in experimental diabetes.
154	16488120	Microsomal monooxygenases - cytochrome P450 (CYP, EC 1.14.14.1) and flavin-containing monooxygenase (FMO, EC 1.14.13.8) - have profound roles in drug metabolism.
155	16488120	While the induction of some metabolic enzymes such as hepatic FMO and intestinal CYP1A, CYP2B is recognized in experimental diabetes, the effect of insulin treatment on FMO and intestinal CYP3A in diabetic animals has not been reported before.
156	16488120	Hepatic FMO1 activity increased in diabetic rats, but it was restored to control value on insulin treatment.
157	16488120	Insulin itself had no effect on FMO1 activity in non-diabetic animals.
158	16488120	A remarkable increase of total CYP content was accompanied by a reduced CYP3A specific enzyme activity in the small intestine of diabetic animals.
159	16488120	Both, hepatic FMO1 and intestinal CYP3A activity correlated with average blood glucose concentration in untreated diabetic rats.
160	16488120	These results indicate that insulin is involved in the regulation of hepatic FMO1 and intestinal CYP3A in rats.
161	16488120	The marked reduction of intestinal CYP3A capacity suggests that diabetes exerts a substantial effect on the activity of most determining intestinal CYP enzyme.
162	16488120	Flavin-containing monooxygenase and cytochrome P450 activities in experimental diabetes.
163	16488120	Microsomal monooxygenases - cytochrome P450 (CYP, EC 1.14.14.1) and flavin-containing monooxygenase (FMO, EC 1.14.13.8) - have profound roles in drug metabolism.
164	16488120	While the induction of some metabolic enzymes such as hepatic FMO and intestinal CYP1A, CYP2B is recognized in experimental diabetes, the effect of insulin treatment on FMO and intestinal CYP3A in diabetic animals has not been reported before.
165	16488120	Hepatic FMO1 activity increased in diabetic rats, but it was restored to control value on insulin treatment.
166	16488120	Insulin itself had no effect on FMO1 activity in non-diabetic animals.
167	16488120	A remarkable increase of total CYP content was accompanied by a reduced CYP3A specific enzyme activity in the small intestine of diabetic animals.
168	16488120	Both, hepatic FMO1 and intestinal CYP3A activity correlated with average blood glucose concentration in untreated diabetic rats.
169	16488120	These results indicate that insulin is involved in the regulation of hepatic FMO1 and intestinal CYP3A in rats.
170	16488120	The marked reduction of intestinal CYP3A capacity suggests that diabetes exerts a substantial effect on the activity of most determining intestinal CYP enzyme.
171	16488120	Flavin-containing monooxygenase and cytochrome P450 activities in experimental diabetes.
172	16488120	Microsomal monooxygenases - cytochrome P450 (CYP, EC 1.14.14.1) and flavin-containing monooxygenase (FMO, EC 1.14.13.8) - have profound roles in drug metabolism.
173	16488120	While the induction of some metabolic enzymes such as hepatic FMO and intestinal CYP1A, CYP2B is recognized in experimental diabetes, the effect of insulin treatment on FMO and intestinal CYP3A in diabetic animals has not been reported before.
174	16488120	Hepatic FMO1 activity increased in diabetic rats, but it was restored to control value on insulin treatment.
175	16488120	Insulin itself had no effect on FMO1 activity in non-diabetic animals.
176	16488120	A remarkable increase of total CYP content was accompanied by a reduced CYP3A specific enzyme activity in the small intestine of diabetic animals.
177	16488120	Both, hepatic FMO1 and intestinal CYP3A activity correlated with average blood glucose concentration in untreated diabetic rats.
178	16488120	These results indicate that insulin is involved in the regulation of hepatic FMO1 and intestinal CYP3A in rats.
179	16488120	The marked reduction of intestinal CYP3A capacity suggests that diabetes exerts a substantial effect on the activity of most determining intestinal CYP enzyme.
180	16488120	Flavin-containing monooxygenase and cytochrome P450 activities in experimental diabetes.
181	16488120	Microsomal monooxygenases - cytochrome P450 (CYP, EC 1.14.14.1) and flavin-containing monooxygenase (FMO, EC 1.14.13.8) - have profound roles in drug metabolism.
182	16488120	While the induction of some metabolic enzymes such as hepatic FMO and intestinal CYP1A, CYP2B is recognized in experimental diabetes, the effect of insulin treatment on FMO and intestinal CYP3A in diabetic animals has not been reported before.
183	16488120	Hepatic FMO1 activity increased in diabetic rats, but it was restored to control value on insulin treatment.
184	16488120	Insulin itself had no effect on FMO1 activity in non-diabetic animals.
185	16488120	A remarkable increase of total CYP content was accompanied by a reduced CYP3A specific enzyme activity in the small intestine of diabetic animals.
186	16488120	Both, hepatic FMO1 and intestinal CYP3A activity correlated with average blood glucose concentration in untreated diabetic rats.
187	16488120	These results indicate that insulin is involved in the regulation of hepatic FMO1 and intestinal CYP3A in rats.
188	16488120	The marked reduction of intestinal CYP3A capacity suggests that diabetes exerts a substantial effect on the activity of most determining intestinal CYP enzyme.
189	16679742	The nuclear receptor constitutive androstane receptor (CAR), a key transcription factor for the expression of cytochrome P450 (CYP) 2B genes, resides in the cytoplasm under untreated conditions and translocates into the nucleus upon xenobiotic exposure.
190	16679742	CAR forms a multiprotein complex including heat shock protein 90 in the cytoplasm as the glucocorticoid receptor, and it is likely that protein phosphatase 2A plays a critical role in the first step of CAR nuclear translocation.
191	16679742	In obese mice fed a high-fat diet, however, hepatic CYP3A levels are drastically decreased without any significant changes in the expression of nuclear receptors including the pregnane X receptor and hepatocyte nuclear factor-4, which are known to be key transcription factors in the expression of CYP3A genes.
192	17912464	Evaluation of genotype distributions by the chi-square test revealed that the 13989-->G (Ile118Val) polymorphism of the cytochrome P450, subfamily IIIA, polypeptide 4 gene (CYP3A4) was significantly (false discovery rate, 0.000009) associated with the prevalence of type 2 diabetes mellitus.
193	18427905	Assessment of a new chemical entity for cytochrome P450 (CYP) enzyme induction at an early stage in discovery is crucial to prevent potential drug-drug interactions.
194	18427905	CYP3A, the most abundant CYP isoform in the liver, metabolizes approximately 50% of drugs currently on the market and is also a highly inducible enzyme.
195	18476487	The expression and in vivo induction of the P450 isoforms CYP2B, CYP2E, CYP3A and CYP4A in liver and lymphocyte samples is determined using Western blot analysis.
196	19022234	By co-treatment with specific inhibitors for cytochrome P450 (CYP) 2C and CYP3A - the major phase I enzymes involved in liver xenobiotic metabolism - we could confirm the prominent role of CYP3A in the bioactivation of troglitazone as well as the role of CYP3A and CYP2C in the activation of diclofenac.
197	19929308	This may be explained by the significantly faster hepatic CL(int) of mirodenafil, owing to increased hepatic CYP1A, CYP2B1/2, CYP2D, and CYP3A expression, and a faster hepatic blood flow rate, compared with control values.
198	20163193	Small intestinal cytochrome P450 (Cyp) 3a expression in TSOD mice was significantly lower than in TSNO mice.
199	20163193	In insulin-treated mice, small intestinal Cyp3a expression was significantly lower than in control mice.
200	20163193	These results suggested that the differences in changes in small intestinal Cyp3a expression between T1DM and T2DM may be due to differences in plasma insulin concentrations.
201	20163193	Small intestinal cytochrome P450 (Cyp) 3a expression in TSOD mice was significantly lower than in TSNO mice.
202	20163193	In insulin-treated mice, small intestinal Cyp3a expression was significantly lower than in control mice.
203	20163193	These results suggested that the differences in changes in small intestinal Cyp3a expression between T1DM and T2DM may be due to differences in plasma insulin concentrations.
204	20736321	Hepatic gene expression of Cyp2b10, Cyp2c29, Cyp3a11, Cyp2e1, Cyp4a10, Nr1i2, Nr1i3, slco1a1, slco1a4, slco1b2, abcb1b, abcc2, and abcg2 was examined using the real-time polymerase chain reaction method in male db/db mice, a commonly used type II diabetes model.
205	20736321	Functional analysis was conducted in hepatic microsomes for Cyp2b, Cyp2c, and Cyp3a using cytochrome P450-specific substrates.
206	20736321	No expression changes were observed for Cyp2e1, Nr1i2, Nr1i3, abcc2, and abcg2.