CYP2E1: Biochemistry, toxicology, regulation and function in ethanol-induced liver injury

被引:118
作者
Kessova, I [1 ]
Cederbaum, AI [1 ]
机构
[1] Mt Sinai Sch Med, Dept Pharmacol & Biol Chem, New York, NY 10029 USA
关键词
D O I
10.2174/1566524033479609
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Ethanol-induced oxidative stress appears to play a major role in mechanisms by which ethanol causes liver injury. Many pathways have been suggested to contribute to the ability of ethanol to induce a state of oxidative stress. One central pathway appears to be the induction of the CYP2E1 form of cytochrome P450 enzymes by ethanol. CYP2E1 is of interest because of its ability to metabolize and activate many toxicological substrates, including ethanol, to more reactive, toxic products. Levels of CYP2E1 are elevated under a variety of physiological and pathophysiological conditions, and after acute and chronic alcohol treatment. CYP2E1 is also an effective generator of reactive oxygen species such as the superoxide anion radical and hydrogen peroxide, and in the presence of iron catalysts, produces powerful oxidants such as the hydroxyl radical. This Review Article summarizes some of the biochemical and toxicological properties of CYP2E1, and briefly describes the use of HepG2 cell lines developed to constitutively express the human CYP2E1 in assessing the actions of CYP2E1. Regulation of CYP2E1 is quite complex and will be briefly reviewed. Possible therapeutic implications for treatment of alcoholic liver injury by inhibition of CYP2E1 or CYP2E1-dependent oxidative stress will be discussed, followed by some future directions which may help to understand the actions of CYP2E1 and its role in alcoholic liver injury.
引用
收藏
页码:509 / 518
页数:10
相关论文
共 142 条
[91]   Metallothionein 2A induction by zinc protects HepG2 cells against CYP2E1-dependent toxicity [J].
Pérez, MJ ;
Cederbaum, AI .
FREE RADICAL BIOLOGY AND MEDICINE, 2003, 34 (04) :443-455
[92]   Antioxidant and pro-oxidant effects of a manganese porphyrin complex against CYP2E1-dependent toxicity [J].
Pérez, MJ ;
Cederbaum, AI .
FREE RADICAL BIOLOGY AND MEDICINE, 2002, 33 (01) :111-127
[93]   Spin trapping agents (Tempol and POBN) protect HepG2 cells overexpressing CYP2E1 against arachidonic acid toxicity [J].
Pérez, MJ ;
Cederbaum, AI .
FREE RADICAL BIOLOGY AND MEDICINE, 2001, 30 (07) :734-746
[94]  
PORTER TD, 1989, MOL PHARMACOL, V36, P61
[95]   INCREASED NADPH-DEPENDENT CHEMI-LUMINESCENCE BY MICROSOMES AFTER CHRONIC ETHANOL-CONSUMPTION [J].
PUNTARULO, S ;
CEDERBAUM, AI .
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 1988, 266 (02) :435-445
[96]   INCREASED NADPH-DEPENDENT AND NADH-DEPENDENT PRODUCTION OF SUPEROXIDE AND HYDROXYL RADICAL BY MICROSOMES AFTER CHRONIC ETHANOL TREATMENT [J].
RASHBASTEP, J ;
TURRO, NJ ;
CEDERBAUM, AI .
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 1993, 300 (01) :401-408
[97]   BIOACTIVATION OF HALOGENATED HYDROCARBONS BY CYTOCHROME-P4502E1 [J].
RAUCY, JL ;
KRANER, JC ;
LASKER, JM .
CRITICAL REVIEWS IN TOXICOLOGY, 1993, 23 (01) :1-20
[98]  
RAUCY JL, 1991, MOL PHARMACOL, V39, P275
[99]  
ROBERTS BJ, 1995, J BIOL CHEM, V270, P29632
[100]  
Roberts BJ, 1997, J BIOL CHEM, V272, P9771