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Alcohol-induced protein hyperacetylation: Mechanisms and consequences

Alcohol-induced protein hyperacetylation: Mechanisms and consequences

作     者:Blythe D Shepard Pamela L Tuma 

作者机构:Department of Biology The Catholic University of America 620 Michigan Avenue NE Washington DC 20064 United States 

出 版 物:《World Journal of Gastroenterology》 (世界胃肠病学杂志(英文版))

年 卷 期:2009年第15卷第10期

页      面:1219-1230页

核心收录:

学科分类:0831[工学-生物医学工程(可授工学、理学、医学学位)] 100207[医学-影像医学与核医学] 1006[医学-中西医结合] 1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 08[工学] 1010[医学-医学技术(可授医学、理学学位)] 100201[医学-内科学(含:心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 100106[医学-放射医学] 100602[医学-中西医结合临床] 10[医学] 

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

主  题:Ethanol Hepatotoxicity Acetylation Deacetylases Acetyltransferases 

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.

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