Cyclosporin A treatment increases rat soleus muscle oxidative capacities.
Previous studies suggested that administration of cyclosporin A (CsA), an immunosuppressive agent, contributes to the increased fatigability of heart transplant recipients. The aim of this study was to investigate whether CsA itself, without vehicle, affects the function of mitochondria maintained in situ, in rats treated with CsA (25mg/kg/day) dissolved in ethanol and olive oil. Treatment with CsA induced a 16% decrease in slow myosin heavy chain (MHC) associated with a 225% increase in fast MHCIIa. The proportion of fibers expressing type IIa MHC increased as a result of CsA treatment. Soleus from the CsA-treated animals showed an increase in both basal (+85%) and maximal (+37%) mitochondrial respiration (P < 0.001), consistent with a 24% increase in citrate synthase activity, whereas the apparent Km for adenosine diphosphate was unchanged. By itself, CsA has no deleterious effects on muscle oxidative capacity but induces alterations in energy metabolism in accordance with the increased proportion of fast-twitch oxidative fibers.
Sanchez
Hervé
H
Département des facteurs humains, Centre de Recherches du Service de Santé des Armées, BP 87, 38702 La Tronche, France. Sanchezh@wanadoo.fr
N'Guessan
Benoit
B
Ribera
Florence
F
Ventura-Clapier
Renée
R
Bigard
Xavier
X
D000818:Animals; D002950:Citrate (si)-Synthase / Q000187:drug effects / Q000378:metabolism; D016572:Cyclosporine / Q000009:adverse effects*; D016027:Heart Transplantation / Q000009:adverse effects*; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D018763:Muscle Fatigue / Q000187:drug effects* / Q000502:physiology; D018656:Muscle Fibers, Fast-Twitch / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018482:Muscle, Skeletal / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D024462:Myosin Type II / Q000187:drug effects / Q000378:metabolism; D010085:Oxidative Phosphorylation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D007166:Immunosuppressive Agents; D016572:Cyclosporine; D002950:Citrate (si)-Synthase; D024462:Myosin Type II