title: Nmnat2 protects cardiomyocytes from hypertrophy via activation of SIRT6.
abstract: The discovery of sirtuins (SIRT), a family of nicotinamide adenine dinucleotide (NAD)-dependent deacetylases, has indicated that intracellular NAD level is crucial for the hypertrophic response of cardiomyocytes. Nicotinamide mononucleotide adenylyltransferase (Nmnat) is a central enzyme in NAD biosynthesis. Here we revealed that Nmnat2 protein expression and enzyme activity were down-regulated during cardiac hypertrophy. In neonatal rat cardiomyocytes, overexpression of Nmnat2 but not its catalytically inactive mutant blocked angiotensin II (Ang II)-induced cardiac hypertrophy, which was dependent on activation of SIRT6 through maintaining the intracellular NAD level. Our results suggested that modulation of Nmnat2 activity may be beneficial in cardiac hypertrophy.
authors.affiliation: Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Cai
authors.forename: Shan-Shan
authors.initials: SS
authors.lastname: Yu
authors.forename: Shao-Rui
authors.initials: SR
authors.lastname: Chen
authors.forename: Rong-Biao
authors.initials: RB
authors.lastname: Pi
authors.forename: Si
authors.initials: S
authors.lastname: Gao
authors.forename: Hong
authors.initials: H
authors.lastname: Li
authors.forename: Jian-Tao
authors.initials: JT
authors.lastname: Ye
authors.forename: Pei-Qing
authors.initials: PQ
authors.lastname: Liu
mesh_terms: D019732:Amide Synthases / Q000378:metabolism; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D006332:Cardiomegaly / Q000201:enzymology* / Q000473:pathology*; D055785:Gene Knockdown Techniques; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology* / Q000502:physiology; D009243:NAD / Q000378:metabolism; D009612:Nicotinamide-Nucleotide Adenylyltransferase / Q000235:genetics / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D037761:Sirtuins / Q000235:genetics / Q000378:metabolism*; D014018:Tissue Distribution
chemical_list: D007527:Isoenzymes; D009243:NAD; D000804:Angiotensin II; D009612:Nicotinamide-Nucleotide Adenylyltransferase; D046988:Proteasome Endopeptidase Complex; D037761:Sirtuins; C560607:sirtuin 6, rat; D019732:Amide Synthases; C038479:NAD+ synthase