Repetitive stretch suppresses denervation-induced atrophy of soleus muscle in rats.
This study was conducted to examine whether stretch-related mechanical loading on skeletal muscle can suppress denervation-induced muscle atrophy, and if so, to depict the underlying molecular mechanism. Denervated rat soleus muscle was repetitively stretched (every 5 s for 15 min/day) for 2 weeks. Histochemical analysis showed that the cross-sectional area of denervated soleus muscle fibers with repetitive stretching was significantly larger than that of control denervated muscle (P<0.05). We then examined the involvement of the Akt/mammalian target of the rapamycin (mTOR) cascade in the suppressive effects of repetitive stretching on muscle atrophy. Repetitive stretching significantly increased the Akt, p70S6K, and 4E-BP1 phosphorylation in denervated soleus muscle compared to controls (P<0.05). Furthermore, repetitive stretching-induced suppression of muscle atrophy was fully inhibited by rapamycin, a potent inhibitor of mTOR. These results indicate that denervation-induced muscle atrophy is significantly suppressed by stretch-related mechanical loading of the muscle through upregulation of the Akt/mTOR signal pathway.
Agata
Nobuhide
N
Physical and Occupational Therapy Program, Department of Physiology, Nagoya University Graduate School of Medicine, 1-1-20 Daikominami, Higashi-ku, Nagoya, Aichi 4618673, Japan.
Sasai
Nobuaki
N
Inoue-Miyazu
Masumi
M
Kawakami
Keisuke
K
Hayakawa
Kimihide
K
Kobayashi
Kunihiko
K
Sokabe
Masahiro
M
D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D007166:Immunosuppressive Agents / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D009121:Muscle Denervation; D052580:Muscle Stretching Exercises; D018482:Muscle, Skeletal / Q000294:innervation / Q000378:metabolism / Q000503:physiopathology; D009133:Muscular Atrophy / Q000378:metabolism* / Q000503:physiopathology*; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects / Q000502:physiology; D011494:Protein Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D020123:Sirolimus / Q000494:pharmacology; D013314:Stress, Mechanical; D058570:TOR Serine-Threonine Kinases; D015854:Up-Regulation / Q000502:physiology; D016474:Weight-Bearing / Q000502:physiology*
D002352:Carrier Proteins; C499526:Eif4ebp1 protein, rat; D007166:Immunosuppressive Agents; D047908:Intracellular Signaling Peptides and Proteins; D010750:Phosphoproteins; D011494:Protein Kinases; C546845:mTOR protein, rat; D051057:Proto-Oncogene Proteins c-akt; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus