title: PARP-2 knockdown protects cardiomyocytes from hypertrophy via activation of SIRT1.
abstract: Poly(ADP-ribosyl)ation catalyzed by the poly(ADP-ribose) polymerases (PARPs) is an immediate post-translational modification of proteins with a homopolymeric chain of repeating ADP-ribose units. It is involved in various cellular processes, such as cell survival and death, transcription, DNA repair and cell division. Inhibitors of PARPs have been documented to be useful in different pathological conditions. Recently, activation of PARP-1, the founding member of PARP family, has been revealed to participate in the development and progression of cardiac hypertrophy and heart failure. However, the roles of other PARPs in cardiovascular system remain to be clarified. PARP-2 shares 69% similarity with PARP-1 in catalytic domains, but their functions do not fully overlap. In this study, we show the first evidence that PARP-2 is involved in cardiac hypertrophy. The mRNA and protein levels of PARP-2 were significantly increased in AngII-stimulated rat cardiomyocytes as well as in hearts of rats submitted to pressure overload. PARP-2 knockdown protected cardiomyocytes from hypertrophy, which may be attributed to activation of SIRT1. These findings shed new light on the understanding of PARP-2-related cardiomyopathy, and suggest the potential application of PARP-2 inhibitors in cardiac hypertrophy.
authors.affiliation: Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, PR China.
authors.forename: Biao
authors.initials: B
authors.lastname: Geng
authors.forename: Yi
authors.initials: Y
authors.lastname: Cai
authors.forename: Si
authors.initials: S
authors.lastname: Gao
authors.forename: Jing
authors.initials: J
authors.lastname: Lu
authors.forename: Lu
authors.initials: L
authors.lastname: Zhang
authors.forename: Jian
authors.initials: J
authors.lastname: Zou
authors.forename: Min
authors.initials: M
authors.lastname: Liu
authors.forename: Shanshan
authors.initials: S
authors.lastname: Yu
authors.forename: Jiantao
authors.initials: J
authors.lastname: Ye
authors.forename: Peiqing
authors.initials: P
authors.lastname: Liu
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D006332:Cardiomegaly / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D002478:Cells, Cultured; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D056564:Sirtuin 1 / Q000096:biosynthesis* / Q000235:genetics; D014162:Transfection
chemical_list: D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D034741:RNA, Small Interfering; D000804:Angiotensin II; C557783:Parp2 protein, rat; D011065:Poly(ADP-ribose) Polymerases; C488368:Sirt1 protein, rat; D056564:Sirtuin 1