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Liver histone H3 phosphoacetylation (K9S10) by binge ethanol
Author(s) -
Shukla Shivendra D,
Restrepo Ricardo,
Fish Philip,
Lim Robert W
Publication year - 2013
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.27.1_supplement.lb633
Subject(s) - liver injury , in vivo , ethanol , histone h3 , binge drinking , cyp2e1 , histone , epigenetics , medicine , endocrinology , chemistry , in vitro , alcohol , biology , biochemistry , gene , alcohol consumption , genetics , microsome
Binge ethanol drinking is on the rise worldwide and there is epidemiological evidence that it accelerates liver injury. However, the molecular mechanism(s) of binge ethanol induced liver injury are not understood. We have examined if dual site modifications of histone H3 in the liver are affected by binge ethanol in order to ascertain the role of this epigenetic process in the injury. We monitored the levels of phosphoacetylated (acetylated at lysine K9 and phosphorylated at serine S10) histone H3 (H3AcK9PS10) by western blotting. To this end both in vitro primary cultures of hepatocytes, and in vivo animal models were used. Data show that in rat hepatocytes ethanol treatment for 24 hr caused a 3 fold increase in the levels of H3AcK9PS10. In an in vivo model where binge ethanol (3.5g/kg) was given intraperitoneally in rats, the levels of H3AcK9PS10 increased about 4 fold 4 hr after treatment. When rats were chronically treated with ethanol in liquid diet for 4 weeks there was no change in the levels of H3AcK9PS10 compared to pair‐fed control. However, when ethanol binge (3 repeat binge at 5g/kg, at 12 hr intervals) was administered in these chronically exposed rats then about 1.4 fold increase (over control rats) in the levels of H3AcK9PS10 was noted. This was not different from similar binge ethanol effect in control rats. These data were also compared with the liver injury marker CYP2E1. Thus, binge ethanol elicits dual histone modifications in liver in distinctive manner and can be examined both in vitro and in vivo conditions. Such studies have the promise of offering newer targets for controlling binge ethanol induced alcoholic liver disease, a disease for which there is no FDA approved drug.