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The role of calcitonin-gene related peptide (CGRP) in the control of protein metabolism in normal and denervated rat skeletal muscle

Grant number: 11/11003-5
Support Opportunities:Regular Research Grants
Duration: September 01, 2011 - August 31, 2013
Field of knowledge:Biological Sciences - Biochemistry - Metabolism and Bioenergetics
Principal Investigator:Luiz Carlos Carvalho Navegantes
Grantee:Luiz Carlos Carvalho Navegantes
Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Associated researchers:Isis Do Carmo Kettelhut


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)

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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)
MACHADO, JULIANO; MANFREDI, LEANDRO H.; SILVEIRA, WILIAN A.; GONCALVES, DAWIT A. P.; LUSTRINO, DANILO; ZANON, NEUSA M.; KETTELHUT, ISIS C.; NAVEGANTES, LUIZ C.. Calcitonin gene-related peptide inhibits autophagic-lysosomal proteolysis through cAMP/PKA signaling in rat skeletal muscles. INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY, v. 72, p. 40-50, . (12/51456-1, 11/11003-5, 12/05697-7, 12/24524-6, 12/18861-0)
MACHADO, JULIANO; SILVEIRA, WILIAN A.; GONCALVES, DAWIT A.; SCHAVINSKI, ALINE ZANATTA; KHAN, MUZAMIL M.; ZANON, NEUSA M.; DIAZ, MAURICIO BERRIEL; RUDOLF, RUEDIGER; KETTELHUT, ISIS C.; NAVEGANTES, LUIZ C.. alpha-Calcitonin gene-related peptide inhibits autophagy and calpain systems and maintains the stability of neuromuscular junction in denervated muscles. MOLECULAR METABOLISM, v. 28, p. 91-106, . (09/54014-7, 11/11003-5, 12/24524-6, 18/10089-2, 12/18861-0)

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