| First Author | Hashimoto M | Year | 2013 |
| Journal | J Lipid Res | Volume | 54 |
| Issue | 8 | Pages | 2060-8 |
| PubMed ID | 23709690 | Mgi Jnum | J:199576 |
| Mgi Id | MGI:5503246 | Doi | 10.1194/jlr.M033464 |
| Citation | Hashimoto M, et al. (2013) Knockout of mouse Cyp3a gene enhances synthesis of cholesterol and bile acid in the liver. J Lipid Res 54(8):2060-8 |
| abstractText | Here, we studied the effects of cytochrome P450 (CYP)3A deficiency on the mRNA expression of genes encoding regulators of hepatic cholesterol levels using Cyp3a-knockout (Cyp3a(-/-)) mice. The mRNA expression levels of genes encoding enzymes involved in cholesterol biosynthesis in the livers of Cyp3a(-/-) mice were higher than those of wild-type (WT) mice. Nuclear levels of sterol regulatory element-binding protein-2 (SREBP-2), which enhances cholesterol biosynthesis, were also higher in the livers of Cyp3a(-/-) mice. Binding of SREBP-2 to the Hmgcs1 gene promoter was more abundant in the livers of Cyp3a(-/-) mice. These results suggest that deficiency of CYP3A enzymes enhances transcription of genes encoding enzymes involved in cholesterol biosynthesis via activation of SREBP-2. On the other hand, hepatic cholesterol levels in Cyp3a(-/-) mice were 20% lower than those in WT mice. The mRNA expression levels of genes encoding enzymes involved in bile acid synthesis, plasma levels of 7alpha-hydroxy-4-cholesten-3-one and hepatic levels of total bile acid were significantly higher in Cyp3a(-/-) mice than in WT mice. These findings suggest that reduction of hepatic total cholesterol in Cyp3a(-/-) mice would be the consequence of enhanced bile acid synthesis. Therefore, CYP3A enzymes appear to play roles in the synthesis of cholesterol and bile acid in vivo. |
