| Grant number: | 11/11003-5 |
| Support type: | Regular Research Grants |
| Duration: | September 01, 2011 - August 31, 2013 |
| Field of knowledge: | Biological Sciences - Biochemistry |
| Principal Investigator: | Luiz Carlos Carvalho Navegantes |
| Grantee: | Luiz Carlos Carvalho Navegantes |
| Home Institution: | Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil |
| Assoc. researchers: | Isis Do Carmo Kettelhut |
Abstract
In previous studies from our laboratory, we demonstrated that the sympathetic nervous system, through the activation of adrenoceptors (AR)-beta2, exerts anabolic effects on skeletal muscle protein metabolism of rodents. These effects are modulated by the classical cAMP/PKA pathway and also by the Akt-dependent signaling pathway. The Gene Related Peptide Calcitonin (CGRP) is a neuropeptide co-secreted with acetylcholine in the endplate region which also operates by cAMP-dependent mechanisms. However, its physiological role in muscle protein metabolism is completely unknown. Recent studies have shown that motor denervation results in muscle atrophy and reduces muscle concentrations of CGRP. Considering that cAMP is an important mediator in the sympathetic inhibition of muscle proteolysis, we hypothesized that CGRP, like catecholamines, exerts anti-catabolic effects on skeletal muscle. This research plan will evaluate the systemic and in vitro effects of CGRP and its antagonist (CGRP8-37) on the expression of genes related to atrophy (atrogenes), activities of different proteolytic systems, as well as the process of synthesis in normal muscles and upon motor denervation (sciatic nerve section). The involvement of PKA and Akt in the metabolic effects induced by CGRP on skeletal muscle will also be investigated. The content of cAMP will be determined by immunoassay, the expression of atrogenes by RT-PCR and the phosphorylation of proteins related to PKA and Akt signaling will be analyzed by Western blotting. These results may contribute to the identification of a new regulatory mechanism of skeletal muscle mass that may be important in the treatment of muscular atrophy upon disuse. (AU)