Recovery of skeletal muscle mass after extensive injury: positive effects of increased contractile activity

• Published in: American Journal of Physiology: Cell Physiology Vol. 294; no. 2; pp. C467 - C476
• Main Authors: Richard-Bulteau, Helene, Serrurier, Bernard, Crassous, Brigitte, Banzet, Sebastien, Peinnequin, Andre, Bigard, Xavier, Koulmann, Nathalie
• Format: Journal Article
• Language: English
• Published: United States American Physiological Society 01.02.2008
• Subjects: Animals; Biochemistry, Molecular Biology; Elapid Venoms; Eukaryotic Initiation Factor-4E; Eukaryotic Initiation Factor-4E - metabolism; Exercise; Exercise Therapy; Female; Hypotheses; Injuries; Kinases; Life Sciences; Muscle Contraction; Muscle Contraction - physiology; Muscle Fibers, Skeletal; Muscle Fibers, Skeletal - metabolism; Muscle Proteins; Muscle Proteins - metabolism; Muscle, Skeletal; Muscle, Skeletal - immunology; Muscle, Skeletal - injuries; Muscle, Skeletal - metabolism; Muscle, Skeletal - physiology; Musculoskeletal system; MyoD Protein; MyoD Protein - metabolism; Neurotoxins; Phosphorylation; Physical Conditioning, Animal; Physical Conditioning, Animal - physiology; Proliferating Cell Nuclear Antigen; Proliferating Cell Nuclear Antigen - metabolism; Protein Kinases; Protein Kinases - metabolism; Proteins; Proto-Oncogene Proteins c-akt; Proto-Oncogene Proteins c-akt - metabolism; Rats; Rats, Wistar; Recovery of Function; Recovery of Function - physiology; Regeneration; Regeneration - physiology; Rehabilitation; Ribosomal Protein S6 Kinases, 70-kDa; Ribosomal Protein S6 Kinases, 70-kDa - metabolism; Rodents; TOR Serine-Threonine Kinases; Up-Regulation; Up-Regulation - physiology
• ISSN: 0363-6143; 1522-1563
• DOI: 10.1152/ajpcell.00355.2007

Centre de Recherches du Service de Santé des Armées, La Tronche, France Submitted 5 August 2007 ; accepted in final form 4 November 2007 The present study was designed to test the hypothesis that increasing physical activity by running exercise could favor the recovery of muscle mass after extensive injury and to determine the main molecular mechanisms involved. Left soleus muscles of female Wistar rats were degenerated by notexin injection before animals were assigned to either a sedentary group or an exercised group. Both regenerating and contralateral intact muscles from active and sedentary rats were removed 5, 7, 14, 21, 28 and 42 days after injury ( n = 8 rats/group). Increasing contractile activity through running exercise during muscle regeneration ensured the full recovery of muscle mass and muscle cross-sectional area as soon as 21 days after injury, whereas muscle weight remained lower even 42 days postinjury in sedentary rats. Proliferator cell nuclear antigen and MyoD protein expression went on longer in active rats than in sedentary rats. Myogenin protein expression was higher in active animals than in sedentary animals 21 days postinjury. The Akt-mammalian target of rapamycin (mTOR) pathway was activated early during the regeneration process, with further increases of mTOR phosphorylation and its downstream effectors, eukaryotic initiation factor-4E-binding protein-1 and p70 s6k , in active rats compared with sedentary rats ( days 7–14 ). The exercise-induced increase in mTOR phosphorylation, independently of Akt, was associated with decreased levels of phosphorylated AMP-activated protein kinase. Taken together, these results provided evidence that increasing contractile activity during muscle regeneration ensured early and full recovery of muscle mass and suggested that these beneficial effects may be due to a longer proliferative step of myogenic cells and activation of mTOR signaling, independently of Akt, during the maturation step of muscle regeneration. muscle regeneration; myogenic regulatory factors; mitogen-activated protein kinases; mammalian target of rapamycin pathway; AMP-activated protein kinase Address for reprint requests and other correspondence: N. Koulmann, Département des Facteurs Humains, Centre de Recherches du Service de Santé des Armées, La Tronche cedex BP 87-38702, France (e-mail: nkoulmann{at}crssa.net )