Nuclear effects of ethanol-induced proteasome inhibition in liver cells.
Alcohol ingestion causes alteration in several cellular mechanisms, and leads to inflammation, apoptosis, immunological response defects, and fibrosis. These phenomena are associated with significant changes in the epigenetic mechanisms, and subsequently, to liver cell memory. The ubiquitin-proteasome pathway is one of the vital pathways in the cell that becomes dysfunctional as a result of chronic ethanol consumption. Inhibition of the proteasome activity in the nucleus causes changes in the turnover of transcriptional factors, histone modifying enzymes, and therefore, affects epigenetic mechanisms. Alcohol consumption has been associated with an increase in histone acetylation and a decrease in histone methylation, which leads to gene expression changes. DNA and histone modifications that result from ethanol-induced proteasome inhibition are key players in regulating gene expression, especially genes involved in the cell cycle, immunological responses, and metabolism of ethanol. The present review highlights the consequences of ethanol-induced proteasome inhibition in the nucleus of liver cells that are chronically exposed to ethanol.
Bardag-Gorce
Fawzia
F
The Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, 1124 W. Carson St. Torrance, CA 90502, United States. fgorce@labiomed.org
D017209:Apoptosis / Q000187:drug effects; D002467:Cell Nucleus / Q000187:drug effects / Q000473:pathology*; D056486:Chemical and Drug Induced Liver Injury; D004249:DNA Damage / Q000187:drug effects; D000431:Ethanol / Q000633:toxicity*; D006657:Histones / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D061988:Proteasome Inhibitors; D014158:Transcription, Genetic / Q000187:drug effects
D006657:Histones; D061988:Proteasome Inhibitors; D000431:Ethanol; D046988:Proteasome Endopeptidase Complex