Mammalian target of rapamycin complex 1 is involved in differentiation of regenerating myofibers in vivo

• Published in: Muscle & nerve Vol. 42; no. 5; pp. 778 - 787
• Main Authors: Miyabara, Elen H., Conte, Talita C., Silva, Meiricris T., Baptista, Igor L., Bueno Jr, Carlos, Fiamoncini, Jarlei, Lambertucci, Rafael H., Serra, Carmen S., Brum, Patricia C., Pithon-curi, Tania, Curi, Rui, Aoki, Marcelo S., Oliveira, Antonio C., Moriscot, Anselmo S.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01-11-2010; Wiley; Wiley Subscription Services, Inc
• Subjects: Animals; Antibiotics, Antineoplastic - pharmacology; Biological and medical sciences; Blotting, Western; Cell Differentiation - physiology; Cell Proliferation; Freezing; Fundamental and applied biological sciences. Psychology; Immunohistochemistry; Male; Medical sciences; Muscle Contraction - physiology; Muscle Fibers, Skeletal - physiology; Muscle Proteins - biosynthesis; Myosin Heavy Chains - metabolism; neonatal MHC; Organ Size - physiology; Phosphorylation; protein synthesis; Rats; Rats, Wistar; regeneration; Regeneration - physiology; Ribosomal Protein S6 Kinases - metabolism; Rodents; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Sirolimus - pharmacology; skeletal muscle; Striated muscle. Tendons; tetanic contraction; TOR Serine-Threonine Kinases - physiology; Vertebrates: osteoarticular system, musculoskeletal system; Human; Cell proliferation; Myosin heavy chain; Neonatal; Rat; Rodentia; neonatal MHC; Soleus muscle; Striated muscle; Muscle contraction; Recovery; Section; tetanic contraction; Regeneration; Vertebrata; Mammalia; Protein synthesis; skeletal muscle; Muscle mass; Tetanic muscular contraction
• ISSN: 0148-639X; 1097-4598
• DOI: 10.1002/mus.21754

This work was undertaken to provide further insight into the role of mammalian target of rapamycin complex 1 (mTORC1) in skeletal muscle regeneration, focusing on myofiber size recovery. Rats were treated or not with rapamycin, an mTORC1 inhibitor. Soleus muscles were then subjected to cryolesion and analyzed 1, 10, and 21 days later. A decrease in soleus myofiber cross‐section area on post‐cryolesion days 10 and 21 was accentuated by rapamycin, which was also effective in reducing protein synthesis in these freeze‐injured muscles. The incidence of proliferating satellite cells during regeneration was unaltered by rapamycin, although immunolabeling for neonatal myosin heavy chain (MHC) was weaker in cryolesion+rapamycin muscles than in cryolesion‐only muscles. In addition, the decline in tetanic contraction of freeze‐injured muscles was accentuated by rapamycin. This study indicates that mTORC1 plays a key role in the recovery of muscle mass and the differentiation of regenerating myofibers, independently of necrosis and satellite cell proliferation mechanisms. Muscle Nerve 42: 778–787, 2010