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) |
|---|---|
| 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 |
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Keywords
- Cholesterol
- Genetic
- Liver
- Peroxisome-proliferator-activated receptor-γ coactivator-1
- PPARγ;
- Promoter regions
ASJC Scopus subject areas
- Biochemistry
- Molecular Medicine
- Molecular Biology
- Clinical Biochemistry
Cite this
Sterol-independent repression of low density lipoprotein receptor promoter by peroxisome proliferator activated receptor γ coactivator-1α (PGC-1α). / Jeong, Jae Hoon; Cho, Sehyung; Youngmi, Kim Pak.
In: Experimental and Molecular Medicine, Vol. 41, No. 6, 30.06.2009, p. 406-416.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Sterol-independent repression of low density lipoprotein receptor promoter by peroxisome proliferator activated receptor γ coactivator-1α (PGC-1α)
AU - Jeong, Jae Hoon
AU - Cho, Sehyung
AU - Youngmi, Kim Pak
PY - 2009/6/30
Y1 - 2009/6/30
N2 - 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.
AB - 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.
KW - Cholesterol
KW - Genetic
KW - Liver
KW - Peroxisome-proliferator-activated receptor-γ coactivator-1
KW - PPARγ;
KW - Promoter regions
UR - http://www.scopus.com/inward/record.url?scp=67649651489&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=67649651489&partnerID=8YFLogxK
U2 - 10.3858/emm.2009.41.6.046
DO - 10.3858/emm.2009.41.6.046
M3 - Article
C2 - 19322023
AN - SCOPUS:67649651489
VL - 41
SP - 406
EP - 416
JO - Experimental and Molecular Medicine
JF - Experimental and Molecular Medicine
SN - 1226-3613
IS - 6
ER -