Cellular adaptations in soleus muscle during recovery after hindlimb unloading.
OBJECTIVE
We used a model of chronic unloading followed by reloading to examine the apoptotic responses associated with soleus muscle atrophy and subsequent recovery.


METHODS
Male Wistar rats were subjected to hindlimb unloading (HU) for 2 weeks and subsequent reloading for 0, 3, 7 and 14 days. One-half of the HU-reloaded rats were administered cyclosporine A (CsA), a calcineurin (CaN) inhibitor.


RESULTS
There was fibre atrophy (73%) and a decrease in slow type I fibre/myosin heavy chain (MyHC) composition in the soleus muscle after 2 weeks of HU. Fibre size and type I MyHC composition recovered to near the age-matched control levels by recovery day 14 in non-treated, but not in CsA-treated, rats. Myonuclear number was lower and the number of apoptotic nuclei higher in 2-week HU than control rats. These values returned to control levels after 7 and 14 days of recovery, respectively, in both HU-recovery groups. After 2 weeks of HU, the levels of heat shock proteins (Hsp) 60 and 72, mitochondrial cytochrome c oxidase subunit IV (Cox IV), and peroxisome proliferator-activated receptor gamma coactivator 1 (PGC-1) proteins were lower than control. The levels of all of these proteins gradually increased to or above the control levels during cage recovery in both groups.


CONCLUSIONS
Our results indicate that apoptotic mechanisms are involved in the modulation of myonuclear number during chronic unloading and subsequent reloading. Furthermore, it appears that CaN is related to fibre size and phenotype adaptations, but not to apoptotic responses.
Oishi
Y
Y
Laboratory of Muscle Physiology, Faculty of Education, Kumamoto University, Kumamoto, Japan. oishi@gpo.kumamoto-u.ac.jp
Ogata
T
T
Yamamoto
K-i
KI
Terada
M
M
Ohira
T
T
Ohira
Y
Y
Taniguchi
K
K
Roy
R R
RR
D000220:Adaptation, Biological / Q000502:physiology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D019703:Calcineurin / Q000378:metabolism; D065095:Calcineurin Inhibitors; D002467:Cell Nucleus / Q000378:metabolism / Q000473:pathology; D018834:Chaperonin 60 / Q000378:metabolism; D016572:Cyclosporine / Q000494:pharmacology; D003576:Electron Transport Complex IV / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D050884:HSP72 Heat-Shock Proteins / Q000378:metabolism; D019417:Hindlimb Suspension / Q000502:physiology*; D008297:Male; D008931:Mitochondria, Muscle / Q000187:drug effects / Q000201:enzymology; D018657:Muscle Fibers, Slow-Twitch / Q000378:metabolism / Q000473:pathology*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D009133:Muscular Atrophy / Q000473:pathology* / Q000503:physiopathology; D018995:Myosin Heavy Chains / Q000378:metabolism; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D016601:RNA-Binding Proteins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014157:Transcription Factors / Q000378:metabolism
D065095:Calcineurin Inhibitors; D018834:Chaperonin 60; D004791:Enzyme Inhibitors; D050884:HSP72 Heat-Shock Proteins; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C501429:Ppargc1a protein, rat; D016601:RNA-Binding Proteins; D014157:Transcription Factors; D016572:Cyclosporine; D003576:Electron Transport Complex IV; D019703:Calcineurin; D018995:Myosin Heavy Chains