title: The Altered Hepatic Tubulin Code in Alcoholic Liver Disease.
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 α-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 dysfunction are described and how this relates to the onset of liver injury is discussed. Finally, we propose that agents that alter the cellular acetylation state may represent a novel therapeutic strategy for treating liver disease.
authors.affiliation: Department of Biology, The Catholic University of America, Washington, DC 20064, USA. 41groebner@cardinalmail.cua.edu.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Groebner
authors.affiliation: Department of Biology, The Catholic University of America, Washington, DC 20064, USA. tuma@cua.edu.
authors.forename: Pamela L
authors.initials: PL
authors.lastname: Tuma
mesh_terms: D000818:Animals; D006801:Humans; D008108:Liver Diseases, Alcoholic / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D014404:Tubulin / Q000378:metabolism*
chemical_list: D014404:Tubulin
keywords: acetylation; ethanol; hepatocytes; liver; microtubules; post-translational modifications; tubulin