Autophagy and ethanol-induced liver injury  

作　　者：Terrence M Donohue Jr 

机构地区：[1]Liver Study Unit, The Omaha Veterans Affairs Medical Center, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, Nebraska 68105, United States

出　　处：《World Journal of Gastroenterology》2009年第10期1178-1185,共8页世界胃肠病学杂志（英文版）

基　　金：Supported by Development funds from the Section of Gastroenterology/Hepatology, University of Nebraska Medical Center;Bridge Research Grant from the University of Nebraska Medical Center;Medical Research Funds from the Department of Veterans Affairs, United States of America

摘　　要：The majority of ethanol metabolism occurs in the liver. Consequently, this organ sustains the greatest damage from ethanol abuse. Ethanol consumption disturbs the delicate balance of protein homeostasis in the liver, causing intracellular protein accumulation due to a disruption of hepatic protein catabolism. Evidence indicates that ethanol or its metabolism impairs trafficking events in the liver, including the process of macroautophagy, which is the engulfment and degradation of cytoplasmic constituents by the lysosomal system. Autophagy is an essential, ongoing cellular process that is highly regulated by nutrients, endocrine factors and signaling pathways. A great number of the genes and gene products that govern the autophagic response have been characterized and the major metabolic and signaling pathways that activate or suppress autophagy have been identified. This review describes the process of autophagy, its regulation and the possible mechanisms by which ethanol disrupts the process of autophagic degradation. The implications of autophagic suppression are discussed in relation to the pathogenesis of alcohol-induced liver injury.The majority of ethanol metabolism occurs in the liver. Consequently, this organ sustains the greatest damage from ethanol abuse. Ethanol consumption disturbs the delicate balance of protein homeostasis in the liver, causing intracellular protein accumulation due to a disruption of hepatic protein catabolism. Evidence indicates that ethanol or its metabolism impairs trafficking events in the liver, including the process of macroautophagy, which is the engulfment and degradation of cytoplasmic constituents by the lysosomal system. Autophagy is an essential, ongoing cellular process that is highly regulated by nutrients, endocrine factors and signaling pathways. A great number of the genes and gene products that govern the autophagic response have been characterized and the major metabolic and signaling pathways that activate or suppress autophagy have been identified. This review describes the process of autophagy, its regulation and the possible mechanisms by which ethanol disrupts the process of autophagic degradation. The implications of autophagic suppression are discussed in relation to the pathogenesis of alcohol-induced liver injury.

关 键 词：AUTOPHAGY AUTOPHAGOSOME Ethanolmetabolism HEPATOMEGALY LYSOSOMES Signal transduction 

分 类 号：R575[医药卫生—消化系统] R329.28[医药卫生—内科学]