Alcohol-induced protein hyperacetylation: Mechanisms and consequences  

作　　者：Blythe D Shepard Pamela L Tuma 

机构地区：[1]Department of Biology, The Catholic University of America, 620 Michigan Avenue, NE Washington, DC 20064, United States

出　　处：《World Journal of Gastroenterology》2009年第10期1219-1230,共12页世界胃肠病学杂志（英文版）

基　　金：Supported by The National Institute of Alcohol Abuse and Alcoholism (R21 AA015683) awarded to P.L.T.

摘　　要：Although the clinical manifestations of alcoholic liver disease are well-described, little is known about the molecular basis of liver injury. Recent studies have indicated that ethanol exposure induces global protein hyperacetylationo This reversible, post- translational modification on the E-amino groups of lysine residues has been shown to modulate multiple, diverse cellular processes ranging from transcriptional activation to microtubule stability. Thus, alcohol- induced protein hyperacetylation likely leads to major physiological consequences that contribute to alcohol-induced hepatotoxicity. Lysine acetylation is controlled by the activities of two opposing enzymes, histone acetyltransferases and histone deacetylases. Currently, efforts are aimed at determining which enzymes are responsible for the increased acetylation of specific substrates. However, the greater challenge will be to determine the physiological ramifications of protein hyperacetylation and how they might contribute to the progression of liver disease. In this review, we will first list and discuss the proteins known to be hyperacetylated in the presence of ethanol. We will then describe what is known about the mechanisms leading to increased protein acetylation and how hyperacetylation may perturb hepatic function.Although the clinical manifestations of alcoholic liver disease are well-described, little is known about the molecular basis of liver injury. Recent studies have indicated that ethanol exposure induces global protein hyperacetylation. This reversible, posttranslational modification on the ε-amino groups of lysine residues has been shown to modulate multiple, diverse cellular processes ranging from transcriptional activation to microtubule stability. Thus, alcoholinduced protein hyperacetylation likely leads to major physiological consequences that contribute to alcohol-induced hepatotoxicity. Lysine acetylation is controlled by the activities of two opposing enzymes, histone acetyltransferases and histone deacetylases. Currently, efforts are aimed at determining which enzymes are responsible for the increased acetylation of specifi c substrates. However, the greater challenge will be to determine the physiological ramifications of protein hyperacetylation and how they might contribute to the progression of liver disease. In this review, we will fi rst list and discuss the proteins known to be hyperacetylated in the presence of ethanol. We will then describe what is known about the mechanisms leading to increased protein acetylation and how hyperacetylation may perturb hepatic function.

关 键 词：ETHANOL HEPATOTOXICITY ACETYLATION DEACETYLASES ACETYLTRANSFERASES 

分 类 号：R575[医药卫生—消化系统] R811.5[医药卫生—内科学]