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

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

• 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: 10/11015-0 - Mecanismos intracelulares envolvidos na ação anticatabólica da adrenalina em músculos esqueléticos de ratos jejuados
• Beneficiário: Flávia Aparecida Graça
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 12/24524-6 - Controle da massa muscular pela via de sinalização do AMPc
• Beneficiário: Isis Do Carmo Kettelhut
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• 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
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• 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
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado