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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Morphological and molecular aspects of immobilization-induced muscle atrophy in rats at different stages of postnatal development: the role of autophagy

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Autor(es):
Foresto, Camila Silva ; Paula-Gomes, Silvia ; Silveira, Wilian Assis ; Graca, Flavia Aparecida ; Kettelhut, Isis do Carmo ; Pinheiro Goncalves, Dawit Albieiro ; Mattiello-Sverzut, Ana Claudia
Número total de Autores: 7
Tipo de documento: Artigo Científico
Fonte: Journal of Applied Physiology; v. 121, n. 3, p. 646-660, SEP 1 2016.
Citações Web of Science: 3
Resumo

Muscle loss occurs following injury and immobilization in adulthood and childhood, which impairs the rehabilitation process; however, far fewer studies have been conducted analyzing atrophic response in infants. This work investigated first the morphological and molecular mechanisms involved in immobilization-induced atrophy in soleus muscles from rats at different stages of postnatal development {[}i.e., weanling (WR) and adult (AR) rats] and, second, the role of autophagy in regulating muscle plasticity during immobilization. Hindlimb immobilization for 10 days reduced muscle mass and fiber cross-sectional area, with more pronounced atrophy in WR, and induced slow-to-fast fiber switching. These effects were accompanied by a decrease in markers of protein synthesis and an increase in autophagy. The ubiquitin (Ub)-ligase MuRF1 and the ubiquitinated proteins were upregulated by immobilization in AR while the autolyzed form of mu-calpain was increased in WR. To further explore the role of autophagy in muscle abnormalities, AR were concomitantly immobilized and treated with colchicine, which blocks autophagosome-lysosome fusion. Colchicine-treated immobilized muscles had exacerbated atrophy and presented degenerative features. Despite Igf1/Akt signaling was downregulated in immobilized muscles from both age groups, Foxo1 and 4 phosphorylation was increased in WR. In the same group of animals, Foxo1 acetylation and Foxo1 and 4 content was increased and decreased, respectively. Our data show that muscle disorders induced by 10-day-immobilization occur in both age-dependent and -independent manners, an understanding that may optimize treatment outcomes in infants. We also provide further evidence that the strong inhibition of autophagy may be ineffective for treating muscle atrophy. (AU)

Processo FAPESP: 13/08553-9 - O papel da beta-arrestina no controle da massa muscular cardíaca e em cultura de cardiomiócitos de roedores
Beneficiário:Sílvia de Paula Gomes
Linha de fomento: Bolsas no Brasil - Pós-Doutorado
Processo FAPESP: 12/18861-0 - A hiperacetilação de FOXO como um mecanismo de supressão do programa gênico atrófico pela sinalização adrenérgica beta2 em músculos esqueléticos de roedores
Beneficiário:Dawit Albieiro Pinheiro Gonçalves
Linha de fomento: Bolsas no Brasil - Pós-Doutorado
Processo FAPESP: 12/24524-6 - Controle da massa muscular pela via de sinalização do AMPc
Beneficiário:Isis Do Carmo Kettelhut
Linha de fomento: Auxílio à Pesquisa - Temático
Processo FAPESP: 10/11015-0 - Mecanismos intracelulares envolvidos na ação anticatabólica da adrenalina em músculos esqueléticos de ratos jejuados
Beneficiário:Flávia Aparecida Graça
Linha de fomento: Bolsas no Brasil - Doutorado