Sterol-independent repression of low density lipoprotein receptor promoter by peroxisome proliferator activated receptor γ coactivator-1α (PGC-1α)

Hoon Jeong Jae, Sehyung Cho, Kim Pak Youngmi

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

Peroxisome proliferator activated receptor (PPAR) γ coactivator-1α (PGC-1α) may be implicated in cholesterol metabolism since PGC-1α co-activates estrogen receptor α (ERα) transactivity and estrogen/ERα induces the transcription of LDL receptor (LDLR). Here, we show that overexpression of PGC-1α in HepG2 cells represses the gene expression of LDLR and does not affect the ERα-induced LDLR expression. PGC-1α suppressed the LDLR promoter-luciferase (pLR1563-luc) activity regardless of cholesterol or functional sterol-regulatory element-1. Serial deletions of the LDLR promoter revealed that the inhibition by PGC-1α required the LDLR promoter regions between -650 bp and -974 bp. Phosphorylation of PGC-1α may not affect the suppression of LDLR expression because treatment of SB202190, a p38 MAP kinase inhibitor, did not reverse the LDLR down-regulation by PGC-1α. This may be the first report showing the repressive function of PGC-1α on gene expression. PGC-1α might be a novel modulator of LDLR gene expression in a sterol-independent manner, and implicated in atherogenesis.

Original languageEnglish (US)
Pages (from-to)406-416
Number of pages11
JournalExperimental and Molecular Medicine
Volume41
Issue number6
DOIs
StatePublished - Jun 30 2009

Keywords

  • Cholesterol
  • Genetic
  • Liver
  • PPARγ;
  • Peroxisome-proliferator-activated receptor-γ coactivator-1
  • Promoter regions

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry

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