Liver proteome analysis in a rodent model of alcoholic steatosis

Billy W. Newton, William K. Russell, David H. Russell, Shashi K. Ramaiah, Arul Jayaraman

Research output: Contribution to journalArticlepeer-review

50 Scopus citations


Alcoholic steatosis (AS) is the initial pathology associated with early stage alcoholic liver disease (ALD) and is characterized by the accumulation of fat in the liver. AS is considered clinically benign because it is reversible, and the progression of AS to alcoholic steatohepatitis (ASH) is a key step in the development of ALD. A two-dimensional gel electrophoresis (2DE)-mass spectrometry (MS) proteomic approach was used to investigate the protein expression pattern underlying AS, as the first step toward determining liver tissue biomarkers for early stage ALD. Several proteins involved in fatty acid and amino acid metabolism were up-regulated in 3- and 6-week ethanol-fed rats relative to isocaloric controls, which suggest a higher energy demand upon chronic exposure to ethanol. In addition, the expression of two proteins associated with alcohol-induced oxidative stress, peroxiredoxin 6 (PRDX6) and aldehyde dehydrogenase 2 (ALDH2), was down-regulated in ethanol fed rats, and suggests an increase in reactive oxygen species and oxidative stress. To investigate if irreversible protein modification arising from oxidative stress during AS impacts protein levels, the extent of carbonylated proteins in the ethanol and isocaloric groups was identified using mass spectrometry. The detection of modified proteins involved in antioxidant functions further supports the notion that oxidative modification of these proteins leads to protein turnover during AS. In addition, the carbonylation of betaine-homocysteine S-methyltransferase, a protein implicated in fatty liver development, in 3-week and 6-week ethanol exposed samples suggests that this protein could be a marker for early stage AS.

Original languageEnglish (US)
Pages (from-to)1663-1671
Number of pages9
JournalJournal of Proteome Research
Issue number4
StatePublished - Apr 3 2009
Externally publishedYes


  • 2DE
  • Carbonylation
  • Liver
  • Mass spectrometry
  • Oxidative stress
  • Steatosis

ASJC Scopus subject areas

  • General Chemistry
  • Biochemistry


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