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EMBO Mol Med ; 5(1): 80-91, 2013 01.
Artigo em Inglês | MEDLINE | ID: mdl-23161797

RESUMO

Maintaining skeletal muscle mass is essential for general health and prevention of disease progression in various neuromuscular conditions. Currently, no treatments are available to prevent progressive loss of muscle mass in any of these conditions. Hibernating mammals are protected from muscle atrophy despite prolonged periods of immobilization and starvation. Here, we describe a mechanism underlying muscle preservation and translate it to non-hibernating mammals. Although Akt has an established role in skeletal muscle homeostasis, we find that serum- and glucocorticoid-inducible kinase 1 (SGK1) regulates muscle mass maintenance via downregulation of proteolysis and autophagy as well as increased protein synthesis during hibernation. We demonstrate that SGK1 is critical for the maintenance of skeletal muscle homeostasis and function in non-hibernating mammals in normal and atrophic conditions such as starvation and immobilization. Our results identify a novel therapeutic target to combat loss of skeletal muscle mass associated with muscle degeneration and atrophy.


Assuntos
Proteínas Imediatamente Precoces/metabolismo , Músculo Esquelético/enzimologia , Atrofia Muscular/prevenção & controle , Proteínas Serina-Treonina Quinases/metabolismo , Animais , Sequência de Bases , Primers do DNA/genética , Ativação Enzimática , Feminino , Fatores de Transcrição Forkhead/antagonistas & inibidores , Hibernação/fisiologia , Homeostase , Proteínas Imediatamente Precoces/genética , Masculino , Camundongos , Camundongos Transgênicos , Músculo Esquelético/patologia , Músculo Esquelético/fisiopatologia , Atrofia Muscular/patologia , Atrofia Muscular/fisiopatologia , Proteínas Serina-Treonina Quinases/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Sciuridae , Transdução de Sinais , Inanição/enzimologia , Inanição/patologia , Serina-Treonina Quinases TOR/metabolismo
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