细胞色素 P450 与酒精性肝病。
Cytochrome P450s and Alcoholic Liver Disease.
机构信息
Department of Health Sciences, College of Public Health, East Tennessee State University Johanson City, TN37614, United States.
Center of Excellence for Inflammation, Infectious Disease and Immunity, East Tennessee State University Johanson City, TN37614, United States.
出版信息
Curr Pharm Des. 2018;24(14):1502-1517. doi: 10.2174/1381612824666180410091511.
Abstract
Alcohol consumption causes liver diseases, designated as Alcoholic Liver Disease (ALD). Because alcohol is detoxified by alcohol dehydrogenase (ADH), a major ethanol metabolism system, the development of ALD was initially believed to be due to malnutrition caused by alcohol metabolism in liver. The discovery of the microsomal ethanol oxidizing system (MEOS) changed this dogma. Cytochrome P450 enzymes (CYP) constitute the major components of MEOS. Cytochrome P450 2E1 (CYP2E1) in MEOS is one of the major ROS generators in liver and is considered to be contributive to ALD. Our labs have been studying the relationship between CYP2E1 and ALD for many years. Recently, we found that human CYP2A6 and its mouse analog CYP2A5 are also induced by alcohol. In mice, the alcohol induction of CYP2A5 is CYP2E1-dependent. Unlike CYP2E1, CYP2A5 protects against the development of ALD. The relationship of CYP2E1, CYP2A5, and ALD is a major focus of this review.
摘要
饮酒会导致肝脏疾病，被指定为酒精性肝病（ALD）。由于酒精在体内是由醇脱氢酶（ADH）代谢的，而 ADH 是主要的乙醇代谢系统，因此最初人们认为 ALD 的发展是由于酒精在肝脏代谢导致的营养不良。微粒体乙醇氧化系统（MEOS）的发现改变了这一观点。细胞色素 P450 酶（CYP）是 MEOS 的主要组成部分。MEOS 中的细胞色素 P450 2E1（CYP2E1）是肝脏中主要的活性氧（ROS）生成酶之一，被认为与 ALD 有关。我们的实验室多年来一直在研究 CYP2E1 与 ALD 之间的关系。最近，我们发现人类 CYP2A6 及其小鼠类似物 CYP2A5 也可被酒精诱导。在小鼠中，CYP2A5 的酒精诱导依赖于 CYP2E1。与 CYP2E1 不同，CYP2A5 可预防 ALD 的发生。CYP2E1、CYP2A5 和 ALD 之间的关系是本综述的重点。
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