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Reverse Yeast Two-hybrid System to Identify Mammalian Nuclear Receptor Residues that Interact with Ligands and/or Antagonists
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Peroxisome proliferator-activated receptorα agonists differentially regulate inhibitor of DNA binding expression in

María Del Carmen González1, J Christopher Corton, Nuria Acero

  • 1Departmento de Biología, Facultades de Farmacia y Medicina, Universidad San Pablo-CEU, Urbanización Montepríncipe, Boadilla del Monte, 28668 Madrid, Spain.

PPAR Research
|June 16, 2012
PubMed

Insights

Peroxisome proliferator-activated receptor alpha (PPARα) activators alter Inhibitor of DNA binding 2 (Id2) gene expression. While fenofibrate decreased Id2 in rats and Wy-14,643 reduced it in mice, fenofibrate increased Id2 in human cells, indicating species-specific effects.

Area of Science:

  • Molecular biology
  • Genetics
  • Pharmacology

Background:

  • Inhibitor of DNA binding 2 (Id2) is a transcription factor involved in cell differentiation and proliferation.
  • Id2 expression is modulated by peroxisome proliferator-activated receptor (PPAR) gamma agonists, linking it to cardiovascular disease.
  • The role of PPAR alpha (PPARα) activators on Id2 expression remains largely unexplored.

Purpose of the Study:

  • To investigate the effect of PPARα activators on Id2 gene expression.
  • To determine if PPARα mediates the observed changes in Id2 expression.
  • To compare the effects of PPARα activators on Id2 expression in rodents and human cells.

Main Methods:

  • Treatment of rats and mice (wild-type and PPARα-null) with fenofibrate and Wy-14,643 (WY).
  • Assessment of hepatic Id2 expression in rodents.
  • Treatment of human hepatocarcinoma (HepG2) cells with fenofibrate and MK-886 (PPARα antagonist).
  • Analysis of Id2 expression in human cells.

Main Results:

  • Fenofibrate decreased hepatic Id2 expression in rats.
  • Wy-14,643 reduced Id2 expression in wild-type mice but not in PPARα-null mice, confirming PPARα mediation in rodents.
  • Fenofibrate increased Id2 expression in HepG2 cells, an effect not blocked by a PPARα antagonist, suggesting a PPARα-independent mechanism in humans.
  • Id2 is confirmed as a gene responsive to PPARα agonists.

Conclusions:

  • PPARα activators modulate Id2 gene expression.
  • The transcriptional effects of PPARα agonists on Id2 exhibit species-specific differences between rodents and humans.
  • These findings highlight the complexity of PPARα signaling and its differential impact across species.

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