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Neural control of protein metabolism

Abstract

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)

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Scientific publications (10)
(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)
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.; et al. 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, . (08/06694-6, 09/07584-2)
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, . (10/12206-4, 08/06694-6, 12/18861-0)
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, . (12/24524-6, 08/06694-6, 12/18861-0, 10/11083-6, 10/11015-0)
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, . (08/06694-6, 12/24524-6, 12/18861-0)
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, . (12/24524-6, 08/06694-6, 10/11083-6, 09/07584-2, 10/11015-0)
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, . (08/06694-6, 09/07584-2, 10/11083-6, 10/11015-0)
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, . (08/06694-6)
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, . (08/06694-6, 09/07584-2, 10/11083-6, 10/11015-0)
LIRA, EDUARDO C.; GONCALVES, DAWIT A. P.; PARREIRAS-E-SILVA, LUCAS T.; ZANON, NEUSA M.; KETTELHUT, ISIS C.; NAVEGANTES, LUIZ C. C.. PHOSPHODIESTERASE-4 INHIBITION REDUCES PROTEOLYSIS AND ATROGENES EXPRESSION IN RAT SKELETAL MUSCLES. MUSCLE & NERVE, v. 44, n. 3, p. 371-381, . (08/06694-6, 09/07584-2)
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, . (08/06694-6, 12/05697-7, 12/24524-6)

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