title: The orphan receptor NOR1 participates in isoprenaline-induced cardiac hypertrophy by regulating PARP-1.
abstract: OBJECTIVE
  The orphan nuclear receptor NOR1 belongs to the NR4A subfamily of the nuclear hormone receptor superfamily, and is involved in glucose and fat metabolism. However, its potential contribution to cardiovascular diseases remains to be assessed. Here, the roles of NOR1 in cardiac hypertrophy induced by isoprenaline and the underlying molecular mechanisms were investigated.
  
  
  METHODS
  NOR1 was expressed in cardiomyocytes treated with isoprenaline. After NOR1 overexpression or knockdown in neonatal rat cardiomyocytes, cellular hypertrophy was monitored by measuring cell surface area and the mRNA of hypertrophic biomarkers. Interactions between NOR1 and PARP-1 were investigated by co-immunoprecipitation. NOR1 expression and PARP-1 activity were measured in rats with cardiac hypertrophy induced by isoprenaline.
  
  
  RESULTS
  Treatment with isoprenaline significantly up-regulated NOR1 expression and PARP-1 activity both in vivo and in vitro. Specific gene silencing of NOR1 attenuated isoprenaline-induced cardiomyocyte hypertrophy, whereas NOR1 overexpression exacerbated cardiac hypertrophy. We identified a physical interaction between NOR1 and PARP-1, which was enhanced by NOR1 transfection and thereby led to PARP-1 activation. Overexpression of NOR1, but not C293Y, a NOR1 mutant lacking the PARP-1 binding activity, increased cellular surface area and the mRNA levels of atrial natriuretic factor and brain natriuretic polypeptide, effects blocked by the PARP-1 inhibitor 3-aminobenzamide or siRNA for PARP-1.
  
  
  CONCLUSIONS
  This is the first evidence that NOR1 was involved in isoprenaline-induced cardiac hypertrophy. The pro-hypertrophic effect of NOR1 can be partly attributed to its regulation of PARP-1 enzymic activity.
authors.affiliation: Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Xiao-Jun
authors.initials: XJ
authors.lastname: Feng
authors.affiliation: Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, China.|Department of Pharmacology, School of Medicine, Jishou University, Jishou, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Gao
authors.affiliation: Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Si
authors.initials: S
authors.lastname: Gao
authors.affiliation: Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Zhuoming
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Lu
authors.affiliation: Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Jiao-Jiao
authors.initials: JJ
authors.lastname: Wang
authors.affiliation: Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Xiao-Yang
authors.initials: XY
authors.lastname: Huang
authors.affiliation: Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Min
authors.initials: M
authors.lastname: Liu
authors.affiliation: Department of Pharmacy, Chengdu Fifth People's Hospital, Chengdu, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zou
authors.affiliation: Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Jian-Tao
authors.initials: JT
authors.lastname: Ye
authors.affiliation: Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Pei-Qing
authors.initials: PQ
authors.lastname: Liu
mesh_terms: D000818:Animals; D009320:Atrial Natriuretic Factor / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D006332:Cardiomegaly / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D055879:Gene Knock-In Techniques; D055785:Gene Knockdown Techniques; D047468:Immunoprecipitation; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology* / Q000633:toxicity; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism; D020097:Natriuretic Peptide, Brain / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D000071137:Poly (ADP-Ribose) Polymerase-1; D000067856:Poly(ADP-ribose) Polymerase Inhibitors / Q000494:pharmacology; D011065:Poly(ADP-ribose) Polymerases / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D013566:Sympathomimetics / Q000494:pharmacology* / Q000633:toxicity; D015854:Up-Regulation
chemical_list: D004268:DNA-Binding Proteins; D009419:Nerve Tissue Proteins; C091333:Nr4a3 protein, rat; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D012333:RNA, Messenger; D013566:Sympathomimetics; D020097:Natriuretic Peptide, Brain; D009320:Atrial Natriuretic Factor; C499322:Parp1 protein, rat; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D007545:Isoproterenol