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Binge alcohol inhibits hepatic class I and II histone deacetylases (HDACs): Potential mechanism for alcohol induced liver injury
Author(s) -
Kirpich Irina,
Gobejishvili Leila,
Kharebava Giorgi,
Zhang Jingwen,
McClain Craig,
Barve Shirish
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.460.2
Subject(s) - acetylation , histone , liver injury , steatosis , epigenetics , endocrinology , medicine , chemistry , fatty liver , alcohol , ethanol , biology , biochemistry , gene , disease
Binge, as well as chronic, alcohol consumption affects global histone acetylation and gene expression. It is becoming increasingly evident that these histone associated epigenetic modifications play a significant role in the development of hepatic pathology. The present work examined the effect of binge alcohol exposure on the expression of class I and II HDACs and their relevant contribution to histone acetylation changes. Methods C57/BL6 mice were gavaged 3 times (12 h intervals) with ethanol at a dose of 4.5 g/kg. Liver injury was evaluated by histopathology and plasma ALT activity. Hepatic HDAC gene expression was assessed by RT PCR. Results Mice binged with ethanol developed microvesicular liver steatosis with elevated serum ALT levels (49.07±5.61 U/L compared to 17.93±0.82 U/L in control group), and significantly increased liver triglycerides (48.02±3.83 vs. 19.90±3.48 mg/g liver). Notably, HDACs 1, 7, 9, 10, and 11 were down regulated while HDAC 3 was found to be up regulated. Suppression of both class I & II HDACs was associated with increased histone H3 acetylation. Conclusion Inhibition of both class I & II HDACs and consequent changes in histone H3 acetylation and gene expression by binge alcohol consumption potentially plays a significant role in the development of hepatic steatosis and injury. This work was supported by NIH grants.