the altered hepatic tubulin code in alcoholic liver disease：酒精性肝病中肝微管蛋白的改变.pdfVIP

Biomolecules 2015, 5, 2140-2159; doi:10.3390/biom5032140 OPEN ACCESS biomolecules ISSN 2218-273X /journal/biomolecules/ Review The Altered Hepatic Tubulin Code in Alcoholic Liver Disease Jennifer L. Groebner and Pamela L. Tuma * Department of Biology, The Catholic University of America, Washington, DC 20064, USA; E-Mail: 41groebner@ * Author to whom correspondence should be addressed; E-Mail: tuma@; Tel.: +1-203-319-6681; Fax: +1-202-319-5721. Academic Editors: Natalia Osna and Kusum Kharbanda Received: 22 July 2015 / Accepted: 24 August 2015 / Published: 18 September 2015 Abstract: The molecular mechanisms that lead to the progression of alcoholic liver disease have been actively examined for decades. Because the hepatic microtubule cytoskeleton supports innumerable cellular processes, it has been the focus of many such mechanistic studies. It has long been appreciated that -tubulin is a major target for modification by highly reactive ethanol metabolites and reactive oxygen species. It is also now apparent that alcohol exposure induces post-translational modifications that are part of the natural repertoire, mainly acetylation. In this review, the modifications of the “tubulin code” are described as well as those adducts by ethanol metabolites. The potential cellular consequences of microtubule modification are described with a focus on alcohol-induced defects in protein trafficking and enhanced steatosis. Possible mechanisms that can explain hepatic dysfunc