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 language | English (US) |
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Pages (from-to) | 406-416 |
Number of pages | 11 |
Journal | Experimental and Molecular Medicine |
Volume | 41 |
Issue number | 6 |
DOIs | |
State | Published - Jun 30 2009 |
Externally published | Yes |
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