title: Ethanol-induced oxidant stress modulates hepatic autophagy and proteasome activity.
abstract: In this review, we describe research findings on the effects of alcohol exposure on two major catabolic systems in liver cells: the ubiquitin-proteasome system (UPS) and autophagy. These hydrolytic systems are not unique to liver cells; they exist in all eukaryotic tissues and cells. However, because the liver is the principal site of ethanol metabolism, it sustains the greatest damage from heavy drinking. Thus, the focus of this review is to specifically describe how ethanol oxidation modulates the activities of the UPS and autophagy and the mechanisms by which these changes contribute to the pathogenesis of alcohol-induced liver injury. Here, we describe the history and the importance of cellular hydrolytic systems, followed by a description of each catabolic pathway and the differential modulation of each by ethanol exposure. Overall, the evidence for an involvement of these catabolic systems in the pathogenesis of alcoholic liver disease is quite strong. It underscores their importance, not only as effective means of cellular recycling and eventual energy generation, but also as essential components of cellular defense.
authors.affiliation: Research Service (151), VA-Nebraska-Western Iowa Health Care System, Omaha, NE 68105, USA; Department of Internal Medicine, College of Medicine, USA; Department of Biochemistry and Molecular Biology, College of Medicine, USA; Department of Pathology and Microbiology, College of Medicine, USA; The Center for Environmental Health and Toxicology, College of Public Health, University of Nebraska Medical Center, Omaha, NE, 68198, USA. Electronic address: tdonohue@unmc.edu.
authors.forename: Terrence M
authors.initials: TM
authors.lastname: Donohue
authors.affiliation: Research Service (151), VA-Nebraska-Western Iowa Health Care System, Omaha, NE 68105, USA; Department of Internal Medicine, College of Medicine, USA.
authors.forename: Paul G
authors.initials: PG
authors.lastname: Thomes
mesh_terms: D000818:Animals; D001343:Autophagy / Q000187:drug effects; D000431:Ethanol / Q000378:metabolism* / Q000494:pharmacology; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D008108:Liver Diseases, Alcoholic / Q000209:etiology / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*
chemical_list: D000431:Ethanol; D046988:Proteasome Endopeptidase Complex
keywords: Autophagy; Ethanol; Steatosis; Ubiquitin proteasome; proteopathy