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Characterization of S-nitrosation of SIRT1 in skeletal muscle in experimental model of aging.

Grant number: 12/14746-1
Support type:Scholarships in Brazil - Master
Effective date (Start): March 01, 2013
Effective date (End): September 30, 2014
Field of knowledge:Health Sciences - Medicine
Principal researcher:Eduardo Rochete Ropelle
Grantee:Luciene Lenhare
Home Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Ageing is associated with the decline of many metabolic parameters. There is clear evidence showing decreased glucose sensitivity and high incidence of type 2 diabetes linked to the ageing process. Recently, SIRT1 (silent mating type information regulator 2 homolog) has emerged as a promising target in the treatment of many metabolic perturbations, including obesity and diabetes, since this protein reduces inflammation and promotes mitochondrial biogenesis through deacetylation and activation of PGC1-a (receptor proliferator-activated peroxissoma gamma coactivator 1-alpha), improving the insulin sensitivity. Loss and gain of function studies also implicates a key role of SIRT1 in muscle function and insulin sensitivity, however, how SIRT1 activity is regulated remains poorly understood. In the other hand, NO-induced protein S-Nitrosation has been increasingly recognized as a post-traductional modification that control protein function. NO production by Nitric oxide synthases isoforms can bond to cysteine residues in target proteins, altering protein structure and function, a mechanism known as S-Nitrosation. However, the effect of S-Nitrosation on SIRT1 activity in the skeletal muscle is unknown. Thus, the aim of this project is investigate the effects of iNOS-mediated SIRT1 S-Nitrosation and insulin sensitivity in skeletal muscle in an ageing model.

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Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
LENHARE, Luciene. Characterization of S-nitrosation of SIRT1 in skeletal muscle in experimental model of aging. 2014. Master's Dissertation - Universidade Estadual de Campinas (UNICAMP). Faculdade de Ciências Médicas.

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