title: Emerging roles of SIRT1 deacetylase in regulating cardiomyocyte survival and hypertrophy.
abstract: Calorie restriction is considered to be the best environmental intervention providing health benefits to mammals. The underlying mechanism of this intervention seems to be controlled by a group of NAD-dependent deacetylases, collectively called sirtuins. In mammals, there are seven sirtuin analogs, SIRT1-SIRT7. The founding member of this family, SIRT1, is shown to protect cardiomyocytes from apoptosis and age-dependent degeneration in a dose dependent manner-protecting cells at low doses but showing detrimental effects at high doses. Studies performed with overexpression or knockdown of SIRT1 indicated that, although it protects cells from oxidative stress and ischemia-reperfusion injury, it promotes hypertrophy of cardiomyocytes. Activation of endogenous SIRT1 by resveratrol also displayed pro-survival and pro-hypertrophic activity of SIRT1. In this article, we review recent findings documenting the role of SIRT1 in regulating cardiac myocyte growth and survival under stress, and the proposed mechanism behind its cardioprotective effects. We also briefly discuss two other sirtuin analogs which have been shown to have cardioprotective effects. This article is part of a special issue entitled "Key Signaling Molecules in Hypertrophy and Heart Failure".
authors.affiliation: Department of Surgery, Committee on Cellular and Molecular Physiology, University of Chicago, Chicago, IL, USA.
authors.forename: Nagalingam R
authors.initials: NR
authors.lastname: Sundaresan
authors.forename: Vinodkumar B
authors.initials: VB
authors.lastname: Pillai
authors.forename: Mahesh P
authors.initials: MP
authors.lastname: Gupta
mesh_terms: D000818:Animals; D006332:Cardiomegaly / Q000378:metabolism* / Q000473:pathology; D002470:Cell Survival; D003331:Coronary Vessels / Q000201:enzymology / Q000503:physiopathology; D020536:Enzyme Activators / Q000627:therapeutic use; D015870:Gene Expression; D006333:Heart Failure / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D006801:Humans; D009206:Myocardium / Q000201:enzymology; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D018919:Neovascularization, Physiologic; D000077185:Resveratrol; D015398:Signal Transduction; D056564:Sirtuin 1 / Q000235:genetics / Q000502:physiology*; D013267:Stilbenes / Q000627:therapeutic use
chemical_list: D020536:Enzyme Activators; D013267:Stilbenes; C447939:SIRT1 protein, human; D056564:Sirtuin 1; D000077185:Resveratrol