title: mTOR pathway inhibition attenuates skeletal muscle growth induced by stretching.
abstract: 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.
authors.affiliation: Faculty of Physical Education, UniFMU, Sao Paulo, Brazil.
authors.forename: Marcelo Saldanha
authors.initials: MS
authors.lastname: Aoki
authors.forename: Elen Haruka
authors.initials: EH
authors.lastname: Miyabara
authors.forename: Antonio Garcia
authors.initials: AG
authors.lastname: Soares
authors.forename: Elisa Tiemi
authors.initials: ET
authors.lastname: Saito
authors.forename: Anselmo Sigari
authors.initials: AS
authors.lastname: Moriscot
mesh_terms: 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
chemical_list: D065095:Calcineurin Inhibitors; D009124:Muscle Proteins; D047428:Protein Kinase Inhibitors; D016572:Cyclosporine; D011494:Protein Kinases; D058570:TOR Serine-Threonine Kinases; D019703:Calcineurin; D020123:Sirolimus