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PHOSPHODIESTERASE-4 INHIBITION REDUCES PROTEOLYSIS AND ATROGENES EXPRESSION IN RAT SKELETAL MUSCLES

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Autor(es):
Lira, Eduardo C. [1] ; Goncalves, Dawit A. P. [1] ; Parreiras-E-Silva, Lucas T. [2] ; Zanon, Neusa M. [1] ; Kettelhut, Isis C. [2] ; Navegantes, Luiz C. C. [1]
Número total de Autores: 6
Afiliação do(s) autor(es):
[1] Univ Sao Paulo, Sch Med Ribeirao Preto, Dept Physiol, BR-14049900 Ribeirao Preto, SP - Brazil
[2] Univ Sao Paulo, Sch Med Ribeirao Preto, Dept Biochem & Immunol, BR-14049900 Ribeirao Preto, SP - Brazil
Número total de Afiliações: 2
Tipo de documento: Artigo Científico
Fonte: MUSCLE & NERVE; v. 44, n. 3, p. 371-381, 2011.
Citações Web of Science: 11
Resumo

Phosphodiesterase (PDE) inhibition reduces skeletal muscle atrophy, but the underlying molecular mechanism remains unclear. We used microdialysis to investigate the effects of different PDE inhibitors on interstitial tyrosine concentration as well as proteolytic activity and atrogenes expression in isolated rat muscle. Rolipram, a PDE-4-selective inhibitor, reduced the interstitial tyrosine concentration and rates of muscle protein degradation. The rolipram-induced muscle cAMP increase was accompanied by a decrease in ubiquitin proteasome system (UPS) activity and atrogin-1 mRNA, a ubiquitin-ligase involved in muscle atrophy. This effect was not associated with Akt phosphorylation but was partially blocked by a protein kinase A inhibitor. Fasting increased atrogin-1, MuRF-1 and LC3b expression, and these effects were markedly suppressed by rolipram. Our data suggest that activation of cAMP signaling by PDE-4 blockade leads to inhibition of UPS activity and atrogenes expression independently of Akt. These findings are important for identifying novel approaches to attenuate muscle atrophy. Muscle Nerve 44: 371-381, 2011 (AU)

Processo FAPESP: 08/06694-6 - Controle neural do metabolismo de proteínas
Beneficiário:Isis Do Carmo Kettelhut
Modalidade de apoio: Auxílio à Pesquisa - Temático
Processo FAPESP: 09/07584-2 - Papel das vias de sinalização da Akt/Foxo e MEK/ERK no efeito antiatrófico mediado pelos adrenoceptores B2 em músculo esquelético de roedores
Beneficiário:Dawit Albieiro Pinheiro Gonçalves
Modalidade de apoio: Bolsas no Brasil - Doutorado