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Neural control of protein metabolism

Grant number: 08/06694-6
Support type:Research Projects - Thematic Grants
Duration: April 01, 2009 - May 31, 2013
Field of knowledge:Biological Sciences - Biochemistry
Principal Investigator:Isis Do Carmo Kettelhut
Grantee:Isis Do Carmo Kettelhut
Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Co-Principal Investigators:Luiz Carlos Carvalho Navegantes
Associated grant(s):12/11875-5 - New methods for investigating skeletal muscle signaling, AV.EXT
Associated scholarship(s):12/05697-7 - Functional interaction between cholinergic and adrenergic systems in the maintenance of muscle mass and motor endplate, BP.DD
10/11015-0 - Intracellular mechanisms involved in anticatabolic effect of the epinephrine in skeletal muscle of fasted rats, BP.DR
10/11083-6 - Role of EPAC in control of protein metabolism in skeletal muscle, BP.DR
09/07584-2 - Role of signaling pathways Akt/Foxo and MEK/ERK on anti-atrophic effect induced by adrenoceptors-B2 in rat skeletal muscle, BP.DR


In contrast to carbohydrate and lipid metabolism, much little is known about the neural, hormonal and nutritional control of protein metabolism in skeletal muscle. Therefore, the main goal of the present project is to investigate the central and peripheral mechanisms by which the Central Nervous System, via sympathetic stimulation, controls the rate of protein metabolism in rat skeletal muscle. More specifically, our goal is to describe the mechanisms (signaling pathway, transcription factors, protein degradation and protein synthesis pathways, etc.) involved in the anabolic and antiatrophy effect promoted by stimulation of b2-adrenoceptors and cAMP in skeletal muscle. Also, we propose to investigate the role of hypothalamus as the neural center that regulates the metabolic actions of catecholamines in skeletal muscle. For this, we will study the intracellular events that take part in the alterations of skeletal muscle protein metabolism in experimental models of sympathetic hyperactivity during short (intracerebroventricular injections of neostigmine, 2-DG or C75) and long periods (chronic intermittent hypoxia). Understanding the signaling and neural pathways that regulate muscle mass provide potential therapeutic targets for the prevention and treatment of muscle wasting in metabolic and neuromuscular diseases. (AU)

Scientific publications (11)
(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)
PRZYGODDA, FRANCIELE; MANFREDI, LEANDRO HENRIQUE; MACHADO, JULIANO; GONCALVES, DAWIT A. P.; ZANON, NEUSA M.; BONAGAMBA, LENI G. H.; MACHADO, BENEDITO H.; KETTELHUT, ISIS C.; NAVEGANTES, LUIZ C. C. Acute intermittent hypoxia in rats activates muscle proteolytic pathways through a gluccorticoid-dependent mechanism. Journal of Applied Physiology, v. 122, n. 5, p. 1114-1124, MAY 2017. Web of Science Citations: 2.
MANFREDI, L. H.; LUSTRINO, D.; MACHADO, J.; SILVEIRA, W. A.; ZANON, N. M.; NAVEGANTES, L. C.; KETTELHUT, I. C. Adrenodemedullation activates the Ca2+-dependent proteolysis in soleus muscles from rats exposed to cold. Journal of Applied Physiology, v. 122, n. 2, p. 317-326, FEB 2017. Web of Science Citations: 1.
MANFREDI, L. H.; PAULA-GOMES, S.; ZANON, N. M.; KETTELHUT, I. C. Myostatin promotes distinct responses on protein metabolism of skeletal and cardiac muscle fibers of rodents. Brazilian Journal of Medical and Biological Research, v. 50, n. 12 2017. Web of Science Citations: 4.
SILVEIRA, W. A.; GONCALVES, D. A.; GRACA, F. A.; ANDRADE-LOPES, A. L.; BERGANTIN, L. B.; ZANON, N. M.; GODINHO, R. O.; KETTELHUT, I. C.; NAVEGANTES, L. C. C. Activating cAMP/PKA signaling in skeletal muscle suppresses the ubiquitin-proteasome-dependent proteolysis: implications for sympathetic regulation. Journal of Applied Physiology, v. 117, n. 1, p. 11-19, JUL 2014. Web of Science Citations: 16.
CASSOLLA, PRISCILA; UCHOA, ERNANE TORRES; MANSUR MACHADO, FREDERICO SANDER; GUIMARAES, JULIANA BOHNEN; RISSATO GAROFALO, MARIA ANTONIETA; BRITO, NILTON DE ALMEIDA; KAGOHARA ELIAS, LUCILA LEICO; COIMBRA, CANDIDO CELSO; KETTELHUT, ISIS DO CARMO; CARVALHO NAVEGANTES, LUIZ CARLOS. The central administration of C75, a fatty acid synthase inhibitor, activates sympathetic outflow and thermogenesis in interscapular brown adipose tissue. PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY, v. 465, n. 12, p. 1687-1699, DEC 2013. Web of Science Citations: 3.
GRACA, FLAVIA A.; GONCALVES, DAWIT A. P.; SILVEIRA, WILIAN A.; LIRA, EDUARDO C.; CHAVES, VALERIA ERNESTANIA; ZANON, NEUSA M.; GAROFALO, MARIA ANTONIETA R.; KETTELHUT, ISIS C.; NAVEGANTES, LUIZ C. C. Epinephrine depletion exacerbates the fasting-induced protein breakdown in fast-twitch skeletal muscles. AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM, v. 305, n. 12, p. E1483-E1494, DEC 2013. Web of Science Citations: 9.
PAULA-GOMES, S.; GONCALVES, D. A. P.; BAVIERA, A. M.; ZANON, N. M.; NAVEGANTES, L. C. C.; KETTELHUT, I. C. Insulin Suppresses Atrophy- and Autophagy-related Genes in Heart Tissue and Cardiomyocytes Through AKT/FOXO Signaling. Hormone and Metabolic Research, v. 45, n. 12, p. 849-855, NOV 2013. Web of Science Citations: 31.
GONCALVES, DAWIT A. P.; SILVEIRA, WILIAN A.; LIRA, EDUARDO C.; GRACA, FLAVIA A.; PAULA-GOMES, SILVIA; ZANON, NEUSA M.; KETTELHUT, ISIS C.; NAVEGANTES, LUIZ C. C. Clenbuterol suppresses proteasomal and lysosomal proteolysis and atrophy-related genes in denervated rat soleus muscles independently of Akt. AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM, v. 302, n. 1, p. E123-E133, JAN 2012. Web of Science Citations: 41.
BAVIERA, AMANDA MARTINS; ZANON, NEUSA MARIA; NAVEGANTES, LUIZ CARLOS C.; KETTELHUT, ISIS CARMO. Involvement of cAMP/Epac/PI3K-dependent pathway in the antiproteolytic effect of epinephrine on rat skeletal muscle. Molecular and Cellular Endocrinology, v. 315, n. 1-2, p. 104-112, FEB 5 2010. Web of Science Citations: 31.
GONCALVES, DAWIT A. P.; LIRA, EDUARDO C.; BAVIERA, AMANDA M.; CAO, PEIRANG; ZANON, NEUSA M.; ARANY, ZOLTAN; BEDARD, NATHALIE; TANKSALE, PREETI; WING, SIMON S.; LECKER, STEWART H.; KETTELHUT, ISIS C.; NAVEGANTES, LUIZ C. C. Mechanisms Involved in 3 `,5 `-Cyclic Adenosine Monophosphate-Mediated Inhibition of the Ubiquitin-Proteasome System in Skeletal Muscle. Endocrinology, v. 150, n. 12, p. 5395-5404, DEC 2009. Web of Science Citations: 29.

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