Liver proteomics in progressive alcoholic steatosis

Harshica Fernando, John E. Wiktorowicz, Kizhake V. Soman, Bhupendra Kaphalia, M Khan, Ghulam Ansari

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Fatty liver is an early stage of alcoholic and nonalcoholic liver disease (ALD and NALD) that progresses to steatohepatitis and other irreversible conditions. In this study, we identified proteins that were differentially expressed in the livers of rats fed 5% ethanol in a Lieber-DeCarli diet daily for 1 and 3. months by discovery proteomics (two-dimensional gel electrophoresis and mass spectrometry) and non-parametric modeling (Multivariate Adaptive Regression Splines). Hepatic fatty infiltration was significantly higher in ethanol-fed animals as compared to controls, and more pronounced at 3. months of ethanol feeding. Discovery proteomics identified changes in the expression of proteins involved in alcohol, lipid, and amino acid metabolism after ethanol feeding. At 1 and 3. months, 12 and 15 different proteins were differentially expressed. Of the identified proteins, down regulation of alcohol dehydrogenase (- 1.6) at 1. month and up regulation of aldehyde dehydrogenase (2.1) at 3. months could be a protective/adaptive mechanism against ethanol toxicity. In addition, betaine-homocysteine S-methyltransferase 2 a protein responsible for methionine metabolism and previously implicated in fatty liver development was significantly up regulated (1.4) at ethanol-induced fatty liver stage (1. month) while peroxiredoxin-1 was down regulated (-1.5) at late fatty liver stage (3. months). Nonparametric analysis of the protein spots yielded fewer proteins and narrowed the list of possible markers and identified d-dopachrome tautomerase (-1.7, at 3. months) as a possible marker for ethanol-induced early steatohepatitis. The observed differential regulation of proteins have potential to serve as biomarker signature for the detection of steatosis and its progression to steatohepatitis once validated in plasma/serum.

Original languageEnglish (US)
Pages (from-to)470-480
Number of pages11
JournalToxicology and Applied Pharmacology
Volume266
Issue number3
DOIs
StatePublished - Feb 1 2013

Fingerprint

Liver
Proteomics
Fatty Liver
Ethanol
Betaine-Homocysteine S-Methyltransferase
Proteins
Metabolism
Peroxiredoxins
Alcoholic Liver Diseases
Aldehyde Dehydrogenase
Alcohol Dehydrogenase
Electrophoresis, Gel, Two-Dimensional
Biomarkers
Nutrition
Electrophoresis
Infiltration
Methionine
Splines
Mass spectrometry
Toxicity

Keywords

  • Alcoholic liver disease
  • Multivariate regression adaptive splines
  • Proteomics
  • Steatohepatitis
  • Steatosis
  • Two dimensional gel electrophoresis

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology

Cite this

Liver proteomics in progressive alcoholic steatosis. / Fernando, Harshica; Wiktorowicz, John E.; Soman, Kizhake V.; Kaphalia, Bhupendra; Khan, M; Ansari, Ghulam.

In: Toxicology and Applied Pharmacology, Vol. 266, No. 3, 01.02.2013, p. 470-480.

Research output: Contribution to journalArticle

Fernando, Harshica ; Wiktorowicz, John E. ; Soman, Kizhake V. ; Kaphalia, Bhupendra ; Khan, M ; Ansari, Ghulam. / Liver proteomics in progressive alcoholic steatosis. In: Toxicology and Applied Pharmacology. 2013 ; Vol. 266, No. 3. pp. 470-480.
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