Search

A possible treatment for Duchenne muscular dystrophies would be to compensate for dystrophin loss by increasing the expression of utrophin, another cytoskeletal protein of the muscle membrane. We previously found that l-arginine, the substrate for nitric oxide synthase, significantly increased utrophin level in muscle and targeted it to the sarcolemma. Here, we have addressed the expected benefit in the mdx mice. Magnetic resonance imaging of lower limbs revealed a 35% reduction of the necrotic zones, confirmed by histological staining of muscles. This regression of the necrosis was also supported by the drastic reduction of Evans blue incorporation, a cell impermeable dye. The creatine kinase level in the serum decreased by 57%. Utrophin level increased 2- to 3-fold in muscles. β-dystroglycan was relocalised with utrophin to the membrane. In the diaphragm, the most affected muscle in mdx mice, the isometric tension increased by 30%, with regression of collagen and of cytoplasmic lipid overloading. Finally, molsidomine, a therapeutic agent that is converted to a NO donor, also attenuated the dystrophic phenotype. Our results suggest that pharmacological activators of the NO pathway may constitute a realistic treatment for Duchenne and Becker muscular dystrophies.

The in vivo spectrum of regenerating muscles shows a specific cross-correlation signal assigned to the (n-3) fatty acyl chain, which peaks during the myoblast fusion phase. In order to identify the origin of this signal and to take all the lipid metabolites into account, we investigated the degeneration-regeneration process by 1H 2D NMR of lipid muscle extracts. We observed an increase in the total amount of lipids during the regeneration process, although the lipid profile did not show any drastic change during this process. The changes in the NMR signal observed in vivo and, in particular, the appearance of the specific (n-3) fatty acyl chain signal appears to arise from mobile lipid compartments located in fusing cells.