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

Mol Cell Biol. 2004 Jul;24(14):6288-97. doi: 10.1128/MCB.24.14.6288-6297.2004.

Abstract

Peroxisome proliferator-activated receptor alpha (PPARalpha) 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 PPARalpha 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 PPARalpha 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 approximately 18-fold decrease in expression and a modest approximately 6-fold increase in expression, respectively. In addition, glycine N-methyltransferase, pyrophosphate phosphohydrolase, and protein phosphatase 1D were down-regulated with PPARalpha activation. These observations establish proteomic profiles reflecting a common and predictable pattern of differential protein expression in livers with PPARalpha activation. We conclude that livers with PPARalpha activation are transcriptionally geared towards fatty acid combustion.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acyl-CoA Oxidase / genetics
  • Acyl-CoA Oxidase / metabolism
  • Amino Acids / metabolism
  • Animals
  • Electrophoresis, Gel, Two-Dimensional / methods
  • Fatty Acids / metabolism
  • Gene Expression Profiling*
  • Liver / chemistry*
  • Liver / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Molecular Sequence Data
  • Proteins / chemistry*
  • Proteins / metabolism*
  • Proteome / analysis*
  • Pyrimidines / administration & dosage
  • Receptors, Cytoplasmic and Nuclear / metabolism*
  • Signal Transduction / physiology
  • Transcription Factors / metabolism*
  • Xenobiotics / metabolism

Substances

  • Amino Acids
  • Fatty Acids
  • Proteins
  • Proteome
  • Pyrimidines
  • Receptors, Cytoplasmic and Nuclear
  • Transcription Factors
  • Xenobiotics
  • pirinixic acid
  • Acyl-CoA Oxidase

Associated data

  • GENBANK/AK088123
  • GENBANK/BC011540
  • GENBANK/BC016078
  • GENBANK/BC025213
  • RefSeq/NM_133732