Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Ontario, Canada.
Curr Drug Metab. 2011 Feb;12(2):186-97. doi: 10.2174/138920011795016845.
Unlike most cytochrome P450 (CYP) enzymes, murine hepatic CYP2A5 is induced during pathological conditions that result in liver injury including hepatotoxicity mediated by xenobiotics, hepatitis caused by various microbial agents and liver neoplasia. Since CYP2A5 metabolizes various important xenobiotics including nicotine and pro-carcinogens such as nitrosamines and aflatoxin B(1), altered gene expression could affect tobacco addiction, hepatotoxicity and hepatocarcinogenesis. This article synthesizes the current knowledge concerning hepatic expression of Cyp2a5 including the transcriptional and post-transcriptional regulatory mechanisms, pathophysiological conditions associated with enzyme induction such as oxidative and endoplasmic reticulum stress and altered lipid and energy homeostasis as well as the known exogenous and putative endogenous substrates. Knowledge of the stimuli responsible for the unique overexpression of CYP2A5 during liver injury may provide clues to a functional role for this enzyme and the impact of variable CYP2A5 expression on xenobiotic metabolism and toxicity, disease development and the adaptive response to hepatocellular stress.
与大多数细胞色素 P450（CYP）酶不同，鼠肝 CYP2A5 在导致肝损伤的病理条件下被诱导，包括外源性物质介导的肝毒性、各种微生物病原体引起的肝炎和肝肿瘤。由于 CYP2A5 代谢多种重要的外源性物质，包括尼古丁和前致癌物，如亚硝胺和黄曲霉毒素 B(1)，改变基因表达可能会影响烟草成瘾、肝毒性和肝癌发生。本文综合了目前关于 Cyp2a5 在肝脏表达的知识，包括转录和转录后调节机制、与酶诱导相关的生理病理条件，如氧化应激和内质网应激以及改变的脂质和能量稳态，以及已知的外源性和推测的内源性底物。了解导致 CYP2A5 在肝损伤期间独特过表达的刺激因素可能为该酶的功能作用提供线索，以及可变的 CYP2A5 表达对异生素代谢和毒性、疾病发展以及对肝细胞应激的适应性反应的影响。
