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Glucocorticoid effects on molecular pathways related to the muscular trophysm in rats and the effect of omega-3 fatty acid (EPA/DHA) on dexametasone-induced muscle atrophy

Grant number: 13/23191-6
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): August 01, 2014
Effective date (End): March 31, 2018
Field of knowledge:Biological Sciences - Physiology - Physiology of Organs and Systems
Cooperation agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
Principal Investigator:Edmar Zanoteli
Grantee:Alan Fappi
Home Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Several conditions can be associated with skeletal muscle atrophy, such as inactivity aging, sepsis, diabetes, cancer and corticosteroids. All of these conditions occur by mechanisms including increased protein degradation and/or reduced protein synthesis. Studies with glucocorticoids such as dexamethasone are performed by analyzing their influence on pathways related to muscular trophism, as the IGF-1/PI-3K/Akt/mTOR, Myostatin/Smad2/3 and Ras/Raf/MEK/ERK pathways, however, the same assessments using others glucocorticoids methylprednisolone and deflazacort are scarce. The Omega-3 has been used beneficially in attenuating muscle atrophy in sepsis and cancer cachexia, however, its effect on muscular atrophy in glucocorticoid apparently potentiates the deleterious effects of muscle. Objectives: To evaluate the effects of different glucocorticoids in different dosages on the molecular pathways that regulate muscle tropism: IGF-1/PI-3k/Akt/mTOR, Myostatin/Smad2/3 and Ras/Raf/MEK/ERK;assess the influence of supplementation of omega-3 on the development of muscle atrophy induced by dexamethasone. Methods: Animals supplemented and non-supplemented with Omega-3 (EPA / DHA) will be submitted to the administration of dexamethasone, while another group of animals receive methylprednisolone and deflazacort, both for 10 days. Will be performed gas chromatography for fatty acid analysis, immunohistochemistry to evaluate the expression of glucocorticoid receptors, real-time PCR and Western blotting for analysis of gene and protein expressions, respectively. (AU)

Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
FAPPI, ALAN; NEVES, JULIANA DE CARVALHO; SANCHES, LEANDRO NUNES; MASSAROTO E SILVA, PEDRO VICTOR; SIKUSAWA, GUILHERME YUITI; CORREA BRANDAO, THAYANE PEREIRA; CHADI, GERSON; ZANOTELI, EDMAR. Skeletal Muscle Response to Deflazacort, Dexamethasone and Methylprednisolone. CELLS, v. 8, n. 5 MAY 2019. Web of Science Citations: 0.
FAPPI, ALAN; NEVES, JULIANA DE C.; KAWASAKI, KARINE A.; BACELAR, LUANA; SANCHES, LEANDRO N.; DA SILVA, FELIPE P.; LARINA-NETO, RUBENS; CHADI, GERSON; ZANOTELI, EDMAR. Omega-3 multiple effects increasing glucocorticoid-induced muscle atrophy: autophagic, AMPK and UPS mechanisms. PHYSIOLOGICAL REPORTS, v. 7, n. 1 JAN 2019. Web of Science Citations: 1.
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)

Please report errors in scientific publications list by writing to: cdi@fapesp.br.