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Cellular bases of the anti-atrophic effects of leucine in the skeletal muscle: role of VPS34

Grant number: 12/13071-0
Support Opportunities:Scholarships in Brazil - Post-Doctoral
Effective date (Start): December 01, 2012
Effective date (End): May 02, 2016
Field of knowledge:Biological Sciences - Morphology - Cytology and Cell Biology
Principal Investigator:Anselmo Sigari Moriscot
Grantee:Igor Luchini Baptista
Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated scholarship(s):14/03106-7 - Role of Parkin in amino acid signaling during skeletal muscle atrophy, BE.EP.PD


The process of muscle atrophy is highly orderly and regulated. It is characterized by a reduction of muscle fiber cross sectional area and protein content, reduction of power contraction, increase of fatigability and insulin resistance. Several pathways are considered important for the loss of skeletal muscle mass, such as the ubiquitin-proteasome pathway and more recently autophagy. We have previously shown that leucine, an essencial aminoacid that has its metabolism initiated on the skeletal muscle, was able to strongly attenuate E3 gene expression and the loss of muscle mass. Despite the clear protective effect of leucine, the underlying cellular/molecular mechanisms are still elusive. Accordingly, VPS34 emerges as a possible player since this protein is responsive to leucine in other models, and components linked to the autophagic process have been described as important regulators of muscle mass. Thererofe this project aims to determine whether leucine modulates VPS34 in atrophying skeletal muscle. Our preliminar results showed a reduction of VPS34 protein expression with change in the pattern of intracelular location during partial immobilization in rats.

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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)
RAMOS, G. V.; CRUZ, A.; SILVA, W. J.; ROZANSKI, A.; BAPTISTA, I. L.; SILVESTRE, J. G.; MORISCOT, A. S.. Thyroid hormone upregulates MDM2 in rat type I fibre: Implications for skeletal muscle mass regulation. ACTA PHYSIOLOGICA, v. 222, n. 4, . (12/13071-0, 17/09398-8, 12/13315-7, 12/22488-2, 15/04090-0)
BAPTISTA, IGOR L.; SILVA, WILLIAN J.; ARTIOLI, GUILHERME G.; GUILHERME, JOAO PAULO L. F.; LEAL, MARCELO L.; AOKI, MARCELO S.; MIYABARA, ELEN H.; MORISCOT, ANSELMO S.. Leucine and HMB Differentially Modulate Proteasome System in Skeletal Muscle under Different Sarcopenic Conditions. PLoS One, v. 8, n. 10, . (12/13071-0, 06/61523-7)

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