PARP-1 suppresses adiponectin expression through poly(ADP-ribosyl)ation of PPARγ in cardiac fibroblasts

Dan Huang, Chongzhe Yang, Yan Wang, Yuhua Liao, Kai Huang

Research output: Contribution to journalArticle

41 Scopus citations

Abstract

Aims: Our aim was to explore the mechanism underlying the transcriptional regulation of adiponectin and its receptors (AdipoR) in cultured rat cardiac fibroblasts. Methods and results: Using western blot and real-time RT-PCR assays, the expression of adiponectin and its receptors was determined. Using Southwestern blot and electrophoretic mobility shift assays, the DNA binding activity of peroxisome proliferator activated receptor γ (PPARγ) was determined. The results showed that adiponectin and AdipoR1 were highly expressed in cultured rat cardiac fibroblasts. Inhibition of poly(ADP-ribose) polymerase 1 (PARP-1) by 3-aminobenzamide, PJ34, or PARP-1 siRNA markedly increased the transcription of adiponectin and AdipoR1 in cultured fibroblasts, mature 3T3 L1 adipocytes, rat myocardium, and white adipose tissue. PPARγ was poly(ADP-ribosyl)ated by PARP-1 in cardiac fibroblasts under basal conditions. Poly(ADP-ribosyl)ation of PPARγ prevented its binding to DNA. Inhibition of PARP-1 enhanced the DNA binding and transactivation of PPARγ and increased the transcription of PPARγ-target genes including CD36, lipoprotein lipase, and leptin in cultured fibroblasts. Conclusion: PARP-1 inhibits adiponectin and AdipoR1 expression as well as PPARγ transactivation through poly(ADP-ribosyl)ation of PPARγ in cultured rat cardiac fibroblasts.

Original languageEnglish (US)
Pages (from-to)98-107
Number of pages10
JournalCardiovascular Research
Volume81
Issue number1
DOIs
StatePublished - Jan 1 2009
Externally publishedYes

Keywords

  • Adiponectin
  • Cardiac fibroblast
  • Peroxisome proliferator activated receptor-gamma
  • Poly(ADP-ribose) polymerase
  • Transcriptional regulation

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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