Protein profiling of mouse livers with peroxisome proliferator-activated receptor α activation

Ruiyin Chu*, Hanjo Lim, Laura Brumfield, Hong Liu, Chris Herring, Peter Ulintz, Janardan K. Reddy, Matthew Davison

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

46 Scopus citations

Abstract

Peroxisome proliferator-activated receptor α (PPARα) is important in the induction of cell-specific pleiotropic responses, including the development of liver tumors, when it is chronically activated by structurally diverse synthetic ligands such as Wy-14,643 or by unmetabolized endogenous ligands resulting from the disruption of the gene encoding acyl coenzyme A (CoA) oxidase (AOX). Alterations in gene expression patterns in livers with PPARα activation were delineated by using a proteomic approach to analyze liver proteins of Wy-14,643-treated and AOX-/- mice. We identified 46 differentially expressed proteins in mouse livers with PPARα activation. Up-regulated proteins, including acetyl-CoA acetyltransferase, farnesyl pyrophosphate synthase, and carnitine O-octanoyltransferase, are involved in fatty acid metabolism, whereas down-regulated proteins, including ketohexokinase, formiminotransferase-cyclodeaminase, fructose-bisphosphatase aldolase B, sarcosine dehydrogenase, and cysteine sulfinic acid decarboxylase, are involved in carbohydrate and amino acid metabolism. Among stress response and xenobiotic metabolism proteins, selenium-binding protein 2 and catalase showed a dramatic ∼18-fold decrease in expression and a modest ∼6-fold increase in expression, respectively. In addition, glycine N-methyltransferase, pyrophosphate phosphohydrolase, and protein phosphatase 1D were down-regulated with PPARα activation. These observations establish proteomic profiles reflecting a common and predictable pattern of differential protein expression in livers with PPARα activation. We conclude that livers with PPARα activation are transcriptionally geared towards fatty acid combustion.

Original languageEnglish (US)
Pages (from-to)6288-6297
Number of pages10
JournalMolecular and cellular biology
Volume24
Issue number14
DOIs
StatePublished - Jul 2004

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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