Exercise prevents impaired autophagy and proteostasis in a model of neurogenic myopathy

Autor(es):Mostrar menos -

Campos, Juliane C. ^[1] ; Baehr, Leslie M. ^[2] ; Gomes, Katia M. S. ^[1] ; Bechara, Luiz R. G. ^[1] ; Voltarelli, Vanessa A. ^[3] ; Bozi, Luiz H. M. ^[1] ; Ribeiro, Marcio A. C. ^[1] ; Ferreira, Nikolas D. ^[1] ; Moreira, Jose B. N. ^{[3, 4]} ; Brum, Patricia C. ^[3] ; Bodine, Sue C. ^[2] ; Ferreira, Julio C. B. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Inst Biomed Sci, BR-05508000 Sao Paulo - Brazil

^[2] Univ Iowa, Endocrinol & Metab Div, Dept Internal Med, Iowa City, IA 52242 - USA

^[3] Univ Sao Paulo, Sch Phys Educ & Sport, BR-05508030 Sao Paulo - Brazil

^[4] Norwegian Univ Sci & Technol, Fac Med & Hlth Sci, Cardiac Exercise Res Grp, N-7006 Trondheim - Norway

• Tipo de documento: Artigo Científico
• Fonte: SCIENTIFIC REPORTS; v. 8, AUG 7 2018.
• Citações Web of Science: 4

Resumo

Increased proteolytic activity has been widely associated with skeletal muscle atrophy. However, elevated proteolysis is also critical for the maintenance of cellular homeostasis by disposing cytotoxic proteins and non-functioning organelles. We recently demonstrated that exercise activates autophagy and re-establishes proteostasis in cardiac diseases. Here, we characterized the impact of exercise on skeletal muscle autophagy and proteostasis in a model of neurogenic myopathy induced by sciatic nerve constriction in rats. Neurogenic myopathy, characterized by progressive atrophy and impaired contractility, was paralleled by accumulation of autophagy-related markers and loss of acute responsiveness to both colchicine and chloroquine. These changes were correlated with elevated levels of damaged proteins, chaperones and pro-apoptotic markers compared to control animals. Sustained autophagy inhibition using chloroquine in rats (50 mg. kg(-1). day(-1)) or muscle-specific deletion of Atg7 in mice was sufficient to impair muscle contractility in control but not in neurogenic myopathy, suggesting that dysfunctional autophagy is critical in skeletal muscle pathophysiology. Finally, 4 weeks of aerobic exercise training (moderate treadmill running, 5x/week, 1 h/day) prior to neurogenic myopathy improved skeletal muscle autophagic flux and proteostasis. These changes were followed by spared muscle mass and better contractility properties. Taken together, our findings suggest the potential value of exercise in maintaining skeletal muscle proteostasis and slowing down the progression of neurogenic myopathy. (AU)

• Processo FAPESP: 12/14416-1 - Controle de qualidade de proteína na disfunção/atrofia muscular esquelética: papel do receptor beta2- adrenérgico
• Beneficiário: Juliane Cruz Campos
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 16/01633-5 - Papel protetor da estimulação beta2-adrenérgica na disfunção/atrofia muscular esquelética: contribuição do sistema lisossomal-autofágico
• Beneficiário: Juliane Cruz Campos
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Doutorado
• Processo FAPESP: 15/22814-5 - Câncer e coração: novos paradigmas de diagnóstico e tratamento
• Beneficiário: Carlos Eduardo Negrão
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 15/20783-5 - Controle de qualidade de proteína na disfunção/atrofia muscular esquelética: papel do receptor ²2- adrenérgico
• Beneficiário: Julio Cesar Batista Ferreira
• Modalidade de apoio: Auxílio à Pesquisa - Regular