Jimenez-Lopez Jose M, Cederbaum Arthur I
Mount Sinai School of Medicine, Department of Pharmacology and Biological Chemistry, New York, NY 10029, USA.
Expert Opin Drug Metab Toxicol. 2005 Dec;1(4):671-85. doi: 10.1517/17425255.1.4.671.
Ethanol-induced oxidative stress plays a major role in the mechanisms by which ethanol causes liver injury. Many pathways contribute to how ethanol induces a state of oxidative stress. One central pathway appears to be the induction, by ethanol, of the CYP2E1 form of cytochrome P450 enzymes. CYP2E1 is of interest because it metabolises and activates many toxicological substrates, including ethanol, to more reactive products. Levels of CYP2E1 are elevated under a variety of physiological and pathophysiological conditions. CYP2E1 is an effective generator of reactive oxygen species. This review summarises some of the biochemical and toxicological properties of CYP2E1, and briefly describes the use of HepG2 cell lines in assessing the actions of CYP2E1. Future directions, which may help to better understand the actions of CYP2E1 and its role in alcoholic liver injury, are suggested.
乙醇诱导的氧化应激在乙醇导致肝损伤的机制中起主要作用。许多途径参与了乙醇如何诱导氧化应激状态。一条核心途径似乎是乙醇诱导细胞色素P450酶的CYP2E1形式。CYP2E1之所以受到关注,是因为它能将包括乙醇在内的许多毒理学底物代谢并激活为更具反应性的产物。在多种生理和病理生理条件下,CYP2E1的水平都会升高。CYP2E1是活性氧的有效产生者。本综述总结了CYP2E1的一些生化和毒理学特性,并简要描述了利用HepG2细胞系评估CYP2E1的作用。文中还提出了未来的研究方向,这可能有助于更好地理解CYP2E1的作用及其在酒精性肝损伤中的作用。