CYP3A4 induction-associated dyslipidemia : a new risk factor for lifestyle disease

本研究发现：1）细胞内胆固醇水平可调控小鼠肝细胞Cyp 3a 11和人肝细胞CYP 3A 4的表达; 2）细胞内胆固醇水平降低可激活SREBP-2，下调CYP 3A基因的表达; 3）胆固醇代谢产物氧化固醇激活LXRα，反式激活CYP 3A基因的表达。此外，我们证明了在培养的小鼠肝细胞中，CYP 3A 4的腺病毒过表达改变了与脂质代谢相关的基因的表达谱。

In this study, we have obtained following findings : 1)the expressions of mouse Cyp3a11 and human CYP3A4 in hepatocytes are modulated by cellular cholesterol levels, 2)SREBP-2 activated by reduced cellular cholesterol levels down-regulates the expressions of CYP3A genes, 3)LXRα, which is activated by cholesterol metabolites oxysterols, transactivates the expression of CYP3A genes. Moreover, we demonstrated that the adenoviral overexpression of CYP3A4 changed the expression profile of genes associated with lipid metabolism in cultured mouse hepatocytes.