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 Opportunities: Scholarships in Brazil - Doctorate
• Start date: August 01, 2014
• End date: March 31, 2018
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: Edmar Zanoteli
• Grantee: Alan Fappi
• Host 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. (13/23191-6)

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. (13/23191-6)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

FAPPI, Alan. Effects of different glucocorticoids on molecular pathways regulating muscle trophism in rats and the effect of EPA / DHA on muscle atrophy induced by dexamethasone. 2018. Doctoral Thesis - Universidade de São Paulo (USP). Faculdade de Medicina (FM/SBD) São Paulo.