Résumé :
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In duchenne’s muscular dystrophy, that is characterized by a progressive skeletal muscle fiber necrosis, the membrane-stabilizing protein dystrophin is missing, and this leads to altered total Ca2+ content in muscle fibers. This study investigated the potential therapeutic benefits of pharmacological tools in reversing the Ca2+ sequestration function of the sarcoplasmic reticulum and improving the functionnal capacity of skeletal muscle of mdx mice. Creatine (CrM: 2,15 mg/mL/day) and L-arginine (L-Arg: 3,75 mg/mL/day) were administred per os to male mdx mice (12 weeks) during 4 weeks. Then, the effectiveness of the treatment was investigated on the contractile protein properties, the sarcoplasmic reticulum Ca2+ uptake and the expression of SERCA1 and calsequestrin in diaphragm muscle of mdx mice. The data demonstrate that after treatments, the maximal Ca2+ activated tension developped by skinned fibers were increased approxymately by 30% (Tmax mdx= 46.8 ± 4.5 mN.mm-2; CrM= 60.3 ± 5.7 mN.mm-2; L-Arg= 61.0 ± 2.8 mN.mm-2). The study of sarcoplasmic function, assessed in skinned fibers and vesicle preparations, shows that the Ca2+ uptake was improved in mdx diaphragm muscle after both pharmacological treatments (Ca2+ uptake mdx= 20.3 ± 1.1 nmole Ca2+.s-1.mg-1; CrM= 22.1 ± 0.6 nmole Ca2+.s-1.mg-1; L-Arg= 26.4 ± 1.1 nmole Ca2+.s-1.mg-1). Furthemore, the overall force of the musculature was tested in living animals using the grip strenght test, the wire test and the rotarod. The results show that the locomotor activity was enhanced and that mdx mice were more resistant to fatigue. During the grip test, the force developped by the four limbs was ameliorated in mdx mice after both treatments (Strength mdx= 4.0 ± 0.1 g.g-1; CrM= 4.2 ± 0.2 g.g-1; L-Arg= 4.7 ± 0.2 g.g-1). In conclusion, the data show that creatine and L-arginine treatments significantly normalized many functionnal and biochemical parameters by acting on events that are related to Ca2+ homeostasis.
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