title: Sirtuin 6 protects cardiomyocytes from hypertrophy in vitro via inhibition of NF-κB-dependent transcriptional activity.
abstract: OBJECTIVE
  Sirtuin 6 (SIRT6) is involved in regulation of glucose and fat metabolism. However, its possible contribution to cardiac dysfunction remains to be determined. In the present study, the effect of SIRT6 on cardiac hypertrophy induced by angiotensin II (AngII) and the underlying molecular mechanisms were investigated.
  
  
  METHODS
  The expression and deacetylase activity of SIRT6 were measured in hypertrophic cardiomyocytes induced by AngII. After SIRT6 overexpression by transfection, or depletion by RNA interference in neonatal rat cardiomyocytes, cellular hypertrophy was monitored by measuring cell surface area and the mRNA levels of hypertrophic biomarkers. Further, the interaction between SIRT6 and the transcription factor NF-κB was investigated by co-immunoprecipitation, confocal immunofluorescence microscopy and luciferase reporter gene assay. The expression and deacetylase activity of SIRT6 were measured in vivo, using the abdominal aortic constriction (AAC) model of cardiac hypertrophy in rats.
  
  
  RESULTS
  In AngII-induced hypertrophic cardiomyocytes and also in AAC-induced hypertrophic hearts, the expression of SIRT6 protein was upregulated, while its deacetylase activity was decreased. Overexpression of wild-type SIRT6 but not its catalytically inactive mutant, attenuated AngII-induced cardiomyocyte hypertrophy. We further demonstrated a physical interaction between SIRT6 and NF-κB catalytic subunit p65, whose transcriptional activity could be repressed by SIRT6 overexpression.
  
  
  CONCLUSIONS
  Our findings suggest that SIRT6 suppressed cardiomyocyte hypertrophy in vitro via inhibition of NF-κB-dependent transcriptional activity and that this effect was dependent on its deacetylase activity.
authors.affiliation: Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Shan-Shan
authors.initials: SS
authors.lastname: Yu
authors.forename: Yi
authors.initials: Y
authors.lastname: Cai
authors.forename: Jian-Tao
authors.initials: JT
authors.lastname: Ye
authors.forename: Rong-Biao
authors.initials: RB
authors.lastname: Pi
authors.forename: Shao-Rui
authors.initials: SR
authors.lastname: Chen
authors.forename: Pei-Qing
authors.initials: PQ
authors.lastname: Liu
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Shen
authors.forename: Yong
authors.initials: Y
authors.lastname: Ji
mesh_terms: D000804:Angiotensin II; D000818:Animals; D001012:Aorta, Abdominal / Q000000981:diagnostic imaging; D006332:Cardiomegaly / Q000139:chemically induced / Q000209:etiology / Q000378:metabolism*; D002478:Cells, Cultured; D003251:Constriction, Pathologic / Q000150:complications / Q000000981:diagnostic imaging; D008297:Male; D032383:Myocytes, Cardiac / Q000378:metabolism*; D009243:NAD / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D037761:Sirtuins / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000502:physiology; D014463:Ultrasonography; D015854:Up-Regulation
chemical_list: D016328:NF-kappa B; D012333:RNA, Messenger; D009243:NAD; D000804:Angiotensin II; C516592:SIRT6 protein, human; D037761:Sirtuins