title: Ethanol intoxication increases hepatic N-lysyl protein acetylation.
abstract: The acetylation of the epsilon-amino group of lysine to form N-acetyl lysine (N-AcLys)-modified proteins regulates the activity of metabolic proteins. Because of the multiple effects of ethanol upon hepatic metabolism, it was hypothesized that ethanol exposure increases the hepatic content of N-AcLys-modified proteins. To test this hypothesis, rats or mice were exposed to ethanol using a liquid diet regimen. Content of N-AcLys-modified proteins was elevated more than 5-fold after 6 weeks of ethanol exposure and persisted after ethanol withdrawal. Use of CYP2E1-knockout mice demonstrated that ethanol-induced acetylation was not dependent solely on CYP2E1 expression. The mitochondrial content of N-AcLys-modified proteins was elevated almost 5-fold following 6 weeks of ethanol exposure. Mitochondrial content of the deacetylase Sirt3 was unchanged by 6 weeks of ethanol exposure. These data indicate ethanol intoxication changes the acetylation status of, and likely the activity of, multiple mitochondrial proteins.
authors.affiliation: Department of Pharmacology, Physiology, and Therapeutics, University of North Dakota, School of Medicine and Health Sciences, 501 N. Columbia Road, Grand Forks, ND 58203-9037, USA. mpicklo@medicine.nodak.edu
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Picklo
mesh_terms: D000107:Acetylation / Q000187:drug effects; D000435:Alcoholic Intoxication / Q000378:metabolism*; D000818:Animals; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics; D000431:Ethanol / Q000633:toxicity*; D005260:Female; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008239:Lysine / Q000378:metabolism*; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D024101:Mitochondrial Proteins / Q000378:metabolism*; D011499:Protein Processing, Post-Translational / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D024101:Mitochondrial Proteins; D000431:Ethanol; D019392:Cytochrome P-450 CYP2E1; D008239:Lysine