Evidence for the role of oxidative stress in the acetylation of histone H3 by ethanol in rat hepatocytes.
The relationship between ethanol-induced oxidative stress and acetylation of histone H3 at lysine 9 (H3AcK9) remains unknown and was therefore investigated in primary cultures of rat hepatocytes. Cells were treated with ethanol, and a select group of pharmacological agents and the status of H3AcK9 and reactive oxygen species (ROS) were monitored. Pretreatment of hepatocytes with N-acetyl cystein (ROS reducer), or dietary antioxidants (quercetin, reserveratrol), or NADPH (reduced nicotinamide adenine dinucleotide phosphate) oxidase inhibitor apocynin, significantly reduced ethanol (50 mM, 24 h) induced increases in ROS and H3AcK9. In contrast, l-buthionine sulfoximine (ROS inducer) and inhibitor of mitochondrial complexes I (rotenone) and III (antimycin) increased ethanol-induced H3AcK9 (P<.01). Oxidative stress also affected ethanol-induced alcohol dehydrogenase 1 mRNA expression. These results demonstrate for the first time that oxidative stress is involved in the ethanol-induced histone H3 acetylation in hepatocytes.
Choudhury
Mahua
M
Department of Medical Pharmacology and Physiology, University of Missouri School of Medicine, One Hospital Drive, Columbia, MO 65212, USA.
Park
Pil-Hoon
PH
Jackson
Daniel
D
Shukla
Shivendra D
SD
D000107:Acetylation; D000111:Acetylcysteine / Q000494:pharmacology; D000426:Alcohol Dehydrogenase / Q000235:genetics; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002478:Cells, Cultured; D000431:Ethanol / Q000494:pharmacology*; D016166:Free Radical Scavengers / Q000494:pharmacology; D005978:Glutathione / Q000187:drug effects / Q000378:metabolism; D022781:Hepatocytes / Q000737:chemistry* / Q000187:drug effects; D006657:Histones / Q000737:chemistry* / Q000187:drug effects; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008239:Lysine / Q000737:chemistry; D008297:Male; D008930:Mitochondria, Liver / Q000737:chemistry; D009249:NADP / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000032:analysis / Q000037:antagonists & inhibitors
D000975:Antioxidants; D016166:Free Radical Scavengers; D006657:Histones; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D000431:Ethanol; D009249:NADP; D006861:Hydrogen Peroxide; D000426:Alcohol Dehydrogenase; D005978:Glutathione; D008239:Lysine; D000111:Acetylcysteine