Chronic ethanol consumption induces global hepatic protein hyperacetylation

Blythe D. Shepard, Dean J Tuma, Pamela L. Tuma

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

Background: Although the clinical manifestations of alcoholic liver disease are well described, little is known about the molecular basis for liver injury. Recent studies have indicated that chronic alcohol consumption leads to the lysine-hyperacetylation of several hepatic proteins, and this list is growing quickly. Methods: To identify other hyperacetylated proteins in ethanol-fed livers, we chose a proteomics approach. Cytosolic and membrane proteins (excluding nuclei) were separated on 2D gels, transferred to PVDF and immunoblotted with antibodies specific for acetylated lysine residues. Hyperacetylated proteins were selected for trypsin digestion and mass spectrometric analysis. Results: In all, 40 proteins were identified, 11 of which are known acetylated proteins. Remarkably, the vast majority of hyperacetylated membrane proteins were mitochondrial residents. Hyperacetylated cytosolic proteins ranged in function from metabolism to cytoskeletal support. Notably, 3 key anti-oxidant proteins were identified whose activities are impaired in ethanol-treated cells. We confirmed that the anti-oxidant enzyme, glutathione peroxidase 1, actin and cortactin are hyperacetylated in ethanol-treated livers. Conclusions: Alcohol-induced hyperacetylation of multiple proteins may contribute to the development of liver injury. The abundance of acetylated mitochondrial proteins further suggests that this modification is important in regulating liver metabolism and when perturbed, may contribute to the progression of a variety of metabolic diseases.

Original languageEnglish (US)
Pages (from-to)280-291
Number of pages12
JournalAlcoholism: Clinical and Experimental Research
Volume34
Issue number2
DOIs
StatePublished - Feb 1 2010

Fingerprint

Ethanol
Liver
Proteins
Oxidants
Metabolism
Lysine
Membrane Proteins
Cortactin
Alcohols
Alcoholic Liver Diseases
Mitochondrial Proteins
Metabolic Diseases
Wounds and Injuries
Alcohol Drinking
Proteomics
Trypsin
Actins
Digestion
Gels
Cells

Keywords

  • Cytoskeleton
  • Ethanol
  • Liver Injury
  • Lysine Acetylation
  • Oxidative Stress

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Toxicology
  • Psychiatry and Mental health

Cite this

Chronic ethanol consumption induces global hepatic protein hyperacetylation. / Shepard, Blythe D.; Tuma, Dean J; Tuma, Pamela L.

In: Alcoholism: Clinical and Experimental Research, Vol. 34, No. 2, 01.02.2010, p. 280-291.

Research output: Contribution to journalArticle

Shepard, Blythe D. ; Tuma, Dean J ; Tuma, Pamela L. / Chronic ethanol consumption induces global hepatic protein hyperacetylation. In: Alcoholism: Clinical and Experimental Research. 2010 ; Vol. 34, No. 2. pp. 280-291.
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