Analysis of expression of glucocorticoid receptor in the skeletal muscle of rats after dexamethasone treatment associated or not with omega-3 supplementation

• Grant number: 14/21390-4
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: March 01, 2015
• End date: February 29, 2016
• Field of knowledge: Biological Sciences - Physiology - General Physiology
• Principal Investigator: Edmar Zanoteli
• Grantee: Karine Akemi Kawasaki
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Muscle atrophy due to the loss of muscle mass current to reduction of the muscle area fibers and / or reducing the amount of fibers. Glucocorticoids cause muscle atrophy through different mechanisms causing reduction protein synthesis, myogenesis inhibition and increase proteolytic activity, mediated by the activation of the ubiquitin proteasome system and lysosomal. Polyunsaturated fatty acids such as Omega-3 (n-3) fatty acids, produce beneficial effects in several physiological processes including cognitive function, anti-inflammatory and immunosuppressive action, one of the forms of n-3 action its to incorporation the cell membrane, which act by modulating different cellular systems, signaling, gene expression and structural membranes function. Several studies have shown that the reposition of n-3 and EPA (eicosapentaenoic acid) are able to attenuate muscle atrophy related to cancer, starvation and septicemia. However, a recent study published in (Fappi et al., 2014) showed that prior and concomitant n-3 supplementation associate a dexamethasone in rats induced a higher muscular atrophy and additionally increase the expression of genes related to muscular atrophy (atrogin-1), being a possible cause for this effect the n-3 influence on muscle glucocorticoid receptors, hypothesis has not yet verified. Objective: To evaluate the expression of glucocorticoids receptors in muscle fiber of rats after dexamethasone treatment associated or not with omega-3 supplementation. Methodology: 60 Male Wistar rats aged between 10 and 12 weeks will be separated into 2 groups (30 animals each) to receive or not n-3 (100mg/kg/d) by gavage for 40 days. In the last 10 days of supplementation, 20 animals from each group will receive dexamethasone (Dx) subcutaneously at doses of 2.5 or 5 mg / kg / day for inducing muscle atrophy, without suspending supplementation with n-3, establishing 6 groups: control; n-3; n-3 + Dx2, 5mg; n-3 + Dx5mg; Dx2, 5mg and Dx5mg. After the trial period the gastrocnemius muscles will be extracted for western blotting analysis (total and phosphorilated glucocorticoid receptors marking). (AU)