mTOR pathway inhibition attenuates skeletal muscle growth induced by stretching.
The present study has aimed to verify the influence of calcineurin and mTOR pathways in skeletal muscle longitudinal growth induced by stretching. Male Wistar rats were treated with cyclosporin-A or rapamycin for 10 days. To promote muscle stretching, casts were positioned so as completely to dorsiflex the plantar-flexor muscles at the ankle in one hind limb during the last 4 days of treatment with either cyclosporin-A or rapamycin. Thereafter, we determined soleus length, weight, protein content, and phenotype. In addition, NFATc1, Raptor, S6K1, 4E-BP1, iNOS, and nNOS gene expression in the soleus were determined by real-time polymerase chain reaction. Soleus length, weight, and protein content were significantly reduced by rapamycin treatment in animals submitted to stretching (P<0.05). In contrast, cyclosporin-A treatment did not alter these parameters. In all cyclosporin-A treated groups, there was a significant reduction in NFATc1 expression (P<0.001). Similarly, a significant reduction was noted in Raptor (P<0.001) and S6K1 (P<0.01) expression in all rapamycin-treated groups. No alteration was observed in 4E-BP1 gene expression among rapamycin-treated groups. Stretching increased gene expression of both NOS isoforms in skeletal muscle. Rapamycin treatment did not interfere with NOS gene expression (P<0.05). Cyclosporin-A treatment did not impair muscle growth induced by stretching but instead caused a marked slow-to-fast fiber shift in the soleus; this was attenuated by stretching. The data presented herein indicate that mTOR pathway is involved in skeletal muscle longitudinal growth.
Aoki
Marcelo Saldanha
MS
Faculty of Physical Education, UniFMU, Sao Paulo, Brazil.
Miyabara
Elen Haruka
EH
Soares
Antonio Garcia
AG
Saito
Elisa Tiemi
ET
Moriscot
Anselmo Sigari
AS
D000818:Animals; D001835:Body Weight; D019703:Calcineurin / Q000502:physiology; D065095:Calcineurin Inhibitors; D016572:Cyclosporine / Q000494:pharmacology; D005786:Gene Expression Regulation; D008297:Male; D009124:Muscle Proteins / Q000032:analysis; D052580:Muscle Stretching Exercises; D018482:Muscle, Skeletal / Q000033:anatomy & histology / Q000737:chemistry / Q000187:drug effects* / Q000254:growth & development*; D009929:Organ Size; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011494:Protein Kinases / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D020123:Sirolimus / Q000494:pharmacology; D058570:TOR Serine-Threonine Kinases
D065095:Calcineurin Inhibitors; D009124:Muscle Proteins; D047428:Protein Kinase Inhibitors; D016572:Cyclosporine; D011494:Protein Kinases; D058570:TOR Serine-Threonine Kinases; D019703:Calcineurin; D020123:Sirolimus