title: A proteomic analysis of liver after ethanol binge in chronically ethanol treated rats.
abstract: 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.
authors.affiliation: Department of Medical Pharmacology & Physiology, University of Missouri, Columbia, MO 65212, USA. shuklasd@missouri.edu.
authors.forename: Annayya R
authors.initials: AR
authors.lastname: Aroor
authors.forename: Lowery J
authors.initials: LJ
authors.lastname: Roy
authors.forename: Ricardo J
authors.initials: RJ
authors.lastname: Restrepo
authors.forename: Brian P
authors.initials: BP
authors.lastname: Mooney
authors.forename: Shivendra D
authors.initials: SD
authors.lastname: Shukla