Zangar R C, Hernandez M, Novak R F
Institute of Chemical Toxicology, Wayne State University, Detroit, Michigan 48201, USA.
Biochem Biophys Res Commun. 1997 Feb 3;231(1):203-5. doi: 10.1006/bbrc.1997.6054.
Human CYP3A, the most abundant hepatic and intestinal cytochrome P450, catalyzes the metabolism of a diverse array of xenobiotics. Dimethyl sulfoxide is a commonly used solvent which has been used therapeutically. Dimethyl sulfoxide effects on CYP3A, CYP2E1, CYP2B and NADPH cytochrome P450 reductase expression in rat liver and in primary cultured rat hepatocytes were examined. Dimethyl sulfoxide increased immunodetectable hepatic CYP3A and CYP2E1 levels approximately 2.5 to 3-fold in the absence of any change in the respective mRNA levels. No change in CYP2B or P450 reductase expression was observed, indicating that dimethyl sulfoxide effects were selective. Dimethyl sulfoxide also increased CYP3A protein in rats pretreated with dexamethasone. In primary cultured rat hepatocytes, dimethyl sulfoxide increased CYP3A and CYP2E1 protein without increasing the respective mRNA levels. These results show that dimethyl sulfoxide, at levels relevant to human exposure, enhances CYP3A and CYP2E1 expression by posttranscriptional mechanisms.
人类细胞色素P450 3A（CYP3A）是肝脏和肠道中含量最丰富的细胞色素P450，可催化多种异生物素的代谢。二甲基亚砜是一种常用溶剂，已用于治疗。研究了二甲基亚砜对大鼠肝脏和原代培养大鼠肝细胞中CYP3A、CYP2E1、CYP2B和NADPH细胞色素P450还原酶表达的影响。在各自mRNA水平无任何变化的情况下，二甲基亚砜使肝脏中可免疫检测到的CYP3A和CYP2E1水平增加了约2.5至3倍。未观察到CYP2B或P450还原酶表达的变化，表明二甲基亚砜的作用具有选择性。二甲基亚砜还增加了用地塞米松预处理的大鼠的CYP3A蛋白。在原代培养的大鼠肝细胞中，二甲基亚砜增加了CYP3A和CYP2E1蛋白，而没有增加各自的mRNA水平。这些结果表明，在与人类接触相关的水平下，二甲基亚砜通过转录后机制增强了CYP3A和CYP2E1的表达。
