Caracterization of S-nitrosation of AMPK-alpha2 on skeletal muscle in aging experimental model

• Grant number: 13/03524-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: May 01, 2013
• End date: April 30, 2014
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Eduardo Rochete Ropelle
• Grantee: Rodrigo Stellzer Gaspar
• Host Institution: Faculdade de Ciências Aplicadas (FCA). Universidade Estadual de Campinas (UNICAMP). Limeira , SP, Brazil

Abstract

Human aging is related to the decline in several physiological functions. Substantial evidence shows that aging has got a narrow relationship with the reduction of muscular metabolism, contributing to the rise of metabolic diseases, such as diabetes mellitus, dyslipidemia, hypertension, and others. Recently, the protein AMPK (AMP-activated protein kinase), an important energetic sensor of the body, emerged as a promising therapeutic target against a series of metabolic disturbances. Studies involving loss and gain of AMPK function ( in its distinct isoforms) indicate that this molecule is crucial for muscular metabolism, once it promotes an improvement in insulin sensitivity, fatty acids oxidation, and mitochondrial biogenesis. In the last decade, some studies have demonstrated that the aging process is related to the loss of the capacity to activate the AMPK, however, little is known about which molecular mechanisms are involved in this process. At the same time, the S-nitrosation of proteins has been valued as one of the main forms of changing the protein activity induced by Nitric Oxide (NO). The NO produced by the different isoforms of Nitric Oxide Synthases (NOS), has the capacity to bind to cysteine residues of several intracellular proteins, modifying its functions through the phenomenon known as S-nitrosation. Although, the role of the S-nitrosation on the activity of the AMPK on the skeletal muscle is yet unknown. Therefore, the objective of this study is to evaluate the participation of inducible NOS (iNOS) on the S-nitrosation of AMPK-alpha2 on skeletal muscle in an experimental aging model. (AU)