title: PARP-1 suppresses adiponectin expression through poly(ADP-ribosyl)ation of PPAR gamma in cardiac fibroblasts.
abstract: OBJECTIVE
  Our aim was to explore the mechanism underlying the transcriptional regulation of adiponectin and its receptors (AdipoR) in cultured rat cardiac fibroblasts.
  
  
  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 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Cardiology, Institute of Cardiovascular Disease, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, People's Republic of China.
authors.forename: Dan
authors.initials: D
authors.lastname: Huang
authors.forename: Chongzhe
authors.initials: C
authors.lastname: Yang
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Yuhua
authors.initials: Y
authors.lastname: Liao
authors.forename: Kai
authors.initials: K
authors.lastname: Huang
mesh_terms: D000246:Adenosine Diphosphate Ribose / Q000378:metabolism*; D052242:Adiponectin / Q000378:metabolism*; D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D018955:CD36 Antigens / Q000378:metabolism; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D006352:Heart Ventricles / Q000166:cytology / Q000378:metabolism*; D020738:Leptin / Q000378:metabolism; D008071:Lipoprotein Lipase / Q000378:metabolism; D008297:Male; D047495:PPAR gamma / Q000378:metabolism*; D010616:Phenanthrenes / Q000494:pharmacology; D000071137:Poly (ADP-Ribose) Polymerase-1; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D054419:Receptors, Adiponectin / Q000378:metabolism
chemical_list: D052242:Adiponectin; D001549:Benzamides; D018955:CD36 Antigens; D004791:Enzyme Inhibitors; D020738:Leptin; C434926:N-(oxo-5,6-dihydrophenanthridin-2-yl)-N,N-dimethylacetamide hydrochloride; D047495:PPAR gamma; D010616:Phenanthrenes; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D012333:RNA, Messenger; D054419:Receptors, Adiponectin; C504339:adiponectin receptor 1, rat; D000246:Adenosine Diphosphate Ribose; C025160:3-aminobenzamide; C499322:Parp1 protein, rat; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D008071:Lipoprotein Lipase