A proteomic analysis of liver after ethanol binge in chronically ethanol treated rats

被引：24
作者：
Aroor, Annayya R. [1 ]
Roy, Lowery J. [2 ]
Restrepo, Ricardo J. [1 ]
Mooney, Brian P. [2 ,3 ]
Shukla, Shivendra D. [1 ]
机构：
[1] Univ Missouri, Dept Med Pharmacol & Physiol, Columbia, MO 65212 USA
[2] Univ Missouri, Prote Ctr, Columbia, MO 65212 USA
[3] Univ Missouri, Div Biochem, Columbia, MO 65212 USA
来源：
PROTEOME SCIENCE | 2012年 / 10卷
关键词：
Binge ethanol; Chronic ethanol; Liver proteomics; CARBONIC-ANHYDRASE-III; NADP(+)-DEPENDENT ISOCITRATE DEHYDROGENASE; GLUTATHIONE-S-TRANSFERASES; OXIDATIVE STRESS; MITOCHONDRIAL PROTEOME; LIPID-PEROXIDATION; GENE-EXPRESSION; DOWN-REGULATION; UP-REGULATION; PROTEINS;
D O I：
10.1186/1477-5956-10-29
中图分类号：
Q5 [生物化学];
学科分类号：
071010 ; 081704 ;
摘要：
Background: Binge ethanol in rats after chronic ethanol exposure augments necrosis and steatosis in the liver. In this study, two-dimensional gel electrophoresis proteomic profiles of liver of control, chronic ethanol, control-binge, and chronic ethanol-binge were compared. Results: The proteomic analysis identified changes in protein abundance among the groups. The levels of carbonic anhydrase 3 (CA3) were decreased after chronic ethanol and decreased further after chronic ethanol-binge. Ethanol binge alone in control rats had no effect on this protein suggesting its possible role in increased susceptibility to injury by binge after chonic ethanol treatment. A protein spot, in which both cytosolic isocitrate dehydrogenase (IDH1) and glutamine synthetase (GS) were identified, showed a small decrease after chronic ethanol binge but western blot demonstrated significant decrease only for glutamine synthetase in chronic ethanol treated rats. The level of gluathione S-transferase mu isoform (GSTM1) increased after chronic ethanol but was lower after chronic ethanol-binge compared to chronic ethanol treatment. The protein levels of the basic form of protein disulfide isomerase associated protein 3 (PDIA3) were significantly decreased and the acidic forms were increased after chronic ethanol-binge but not in chronic ethanol treated rats or ethanol binge in control rats. The significant changes in proteome profile in chronic ethanol binge were accompanied by a marked increase in liver injury as evidenced by enhanced steatosis, necrosis, increased 4-hydroxynonenal labeled proteins, CYP2E1 expression, and decreased histone H2AX phosphorylation. Conclusions: Given the role of CA3, IDH1 and GST in oxidative stress; PDIA3 in protein quality control, apoptosis and DNA repair and decreased glutamine synthetase as a sensitive marker of pericentral liver injury this proteome study of chronic ethanol-binge rat model identifies these proteins for the first time as molecular targets with potential role in progression of liver injury by binge ethanol drinking.
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页数：12
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