Alcohol-induced protein hyperacetylation: mechanisms and consequences.
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 hyperacetylation. This reversible, post-translational modification on the epsilon-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.
Shepard
Blythe D
BD
Department of Biology, The Catholic University of America, 620 Michigan Avenue, NE Washington, DC 20064, United States.
Tuma
Pamela L
PL
D000107:Acetylation / Q000187:drug effects*; D019392:Cytochrome P-450 CYP2E1 / Q000187:drug effects / Q000378:metabolism; D000431:Ethanol / Q000633:toxicity*; D006655:Histone Deacetylases / Q000378:metabolism; D006657:Histones / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D008108:Liver Diseases, Alcoholic / Q000378:metabolism / Q000473:pathology*; D008239:Lysine / Q000378:metabolism; D008870:Microtubules / Q000187:drug effects / Q000473:pathology; D011506:Proteins / Q000187:drug effects / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism
D006657:Histones; D011506:Proteins; D016159:Tumor Suppressor Protein p53; D000431:Ethanol; D019392:Cytochrome P-450 CYP2E1; D006655:Histone Deacetylases; D008239:Lysine