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Role of glucocorticoids in the regulation of Redd1, an inhibitor of muscle protein synthesis, in response to thermal stress

Grant number: 16/24177-5
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): February 01, 2017
Effective date (End): January 31, 2019
Field of knowledge:Biological Sciences - Biochemistry - Metabolism and Bioenergetics
Principal researcher:Luiz Carlos Carvalho Navegantes
Grantee:Vinicius Taboni Lisboa
Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

The adaptive responses to cold involve a series of endocrine, metabolic, cardiovascular and behavioral changes. Recent studies from our laboratory have demonstrated that exposure to cold in rats results in activation of proteolysis and inhibition of skeletal muscle protein synthesis. However, the molecular mechanisms underlying these catabolic effects are not yet known. Therefore, the present work aims to evaluate the role of glucocorticoids in the regulation of Redd1 (Regulated in DNA damage and development 1) as a possible inhibitory mechanism of protein synthesis in response to thermal stress. To this end, rates of muscle protein synthesis will be measured and correlated to gene expression (RT-PCR) and protein levels (Western blotting) of Redd1, as well as the proteins involved in its signaling pathway in different skeletal muscles of adrenalectomized mice exposed to cold (40C) for 3h. The in vivo and in vitro (C2C12 muscle cells) treatment with dexamethasone, a synthetic glucocorticoid, on genes and proteins will also be investigated. Since Redd1 can modulate autophagy in other tissues, this process will be evaluated by analyzing the content of LC3I /II proteins and the autophagic flux in vivo. The understanding of these mechanisms may contribute to the combat of muscle protein catabolism upon stress conditions. (AU)

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