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Effect of therapy with omega 3 in the expression of proteins SOCE in MDX mice

Grant number: 14/16800-9
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): November 01, 2014
Effective date (End): October 31, 2015
Field of knowledge:Biological Sciences - Morphology - Anatomy
Principal Investigator:Renato Ferretti
Grantee:Marina Zanichelli Barbosa
Home Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

Duchenne muscular dystrophy (DMD) is characterized by a progressive muscle disorder related to lack of dystrophin protein with increased Ca2+ uptake in the muscle fibers leading to muscle fiber necrosis, myonecrosis. Ca2+-operated channel entry (SOCE) belong to a complex of selective Ca2+ channels in the sarcolemma, including Orai1 and STIM1, which are present in the sarcoplasmic reticulum (SR) and form a crucial Ca2+ entry pathophysiological mechanism in dystrophinopathies. Until this moment there is no cure for DMD, however several molecular mechanisms have been proposed in an attempt to explain the role of excess Ca2+ as a mediator of myonecrosis and future therapeutic strategies for dystrophinopathies. Omega-3 (©-3) reduced inflammation and levels of TNF-±, specifically by the eicosapentaenoic acid agent (EPA), leading to protection of dystrophic muscle fibers against myonecrosis. Recently, it was observed that ©-3 acts in the control of intracellular Ca2+ regulation by SOCE proteins. In this study, we will evaluate if protection against myonecrosis is related to the activity of SOCE, by increased levels of Orai1 and STIM1 in mdx mice treated with ©-3. We intend to show the Ca2+ regulatory proteins that are related to the protection of the muscle fiber and to identify new drugs that could be used in clinical trials for DMD. Our results aim to better understand the mechanisms involved in the protection of myonecrosis by ©-3, dystrophinopathies progression and identification of targets for alternative drug therapies.