Résumé :
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Duchenne muscular dystrophy (DMD) is the most common genetic disorder characterized by the lack of dystrophin, a sub-sarcolemmal protein necessary for normal muscle functions. Among therapeutic approaches, the upregulation of utrophin to replace defectious dystrophin is developed. Previous studies demonstrate an increase of utrophin labelling, a decrease of necrotic surface, a diminution of creatine kinase release in the serum, and an improvement of isometric strength as consequences of improved NO production via the injection of L-arginine, the substrat for NO synthase or of molsidomine, an NO donor commercialized as Corvasal®. While histology indicates that molsidomine can reverse the degenerating process induced in mdx mice, the mechanism of action on the muscle structure is not really known. We examine the part of the phospholipid composition in membrane myofibers by addressing the phospholipid intensity ratio PC34:2(PC C16:0/C18:2)/PC34:1(PC C16:0/C18:1). This ratio has been demonstrated to be different in normal and dystrophic mice models by in situ MALDI-MS profiling. This variation was recently confirmed by cluster-TOF-SIMS (Time-of-flight Secondary Ion Mass Spectrometry) imaging on human dystrophic tissue sections. On the other hand, cell cultures were performed and the same intensity ratio inversion was shown during the differentiation from myoblasts to myotubes.It was thus suggested that this ratio could be a marker of the regenerating process of muscle cell lines. After the treatment of mdx mice with molsidomine, we evidenced by MALDI-TOF MS profiling a restoration of a membrane lipid composition equivalent to those of wild-type mice. This restoration was associated with an increase of the regeneration process in the mice. This indicates that NO donors restore a normal membrane structure mainly via a regeneration process although the eventuality of a simple compensation of the membrane structure by incorporation of specific class of fatty acids cannot be excluded.
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