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Cardiovascular Research Advance Access [Accepted Manuscript] published online on September 24, 2008
Cardiovascular Research, doi:10.1093/cvr/cvn264
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Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2008. For permissions please email: journals.permissions@oxfordjournals.org.

PARP-1 suppresses adiponectin expression through poly(ADP-ribosyl)ation of PPAR{gamma} in cardiac fibroblasts

Dan Huang1,2, Chongzhe Yang1,2, Yan Wang1, Yuhua Liao1 and Kai Huang1,*

1 Department of Cardiology, Institute of Cardiovascular Disease, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China

* Corresponding Author: Kai Huang, MD PhD, Department of Cardiovascular Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China, 430022. Tel: 86-27-85726360; Fax: 86-27-85756636. Email: huangkai1{at}yahoo.com

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 assay (EMSA) assays, the DNA binding activity of peroxisome proliferator activated receptor {gamma} (PPAR{gamma}) 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. PPAR{gamma} was poly(ADP-ribosyl)ated by PARP-1 in cardiac fibroblasts under basal conditions. Poly(ADP-ribosyl)ation of PPAR{gamma} prevented its binding to DNA. Inhibition of PARP-1 enhanced the DNA binding and transactivation of PPAR{gamma} and increased the transcription of PPAR{gamma}-target genes including CD36, lipoprotein lipase and leptin in cultured fibroblasts.

Conclusion: PARP-1 inhibits adiponectin and AdipoR1 expression as well as PPAR{gamma} transactivation through poly(ADP-ribosyl)ation of PPAR{gamma} in cultured rat cardiac fibroblasts.

Time for primary review: 24 days

2 Contributes equally as the first author.


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