Mdx mouse skeletal muscle: could a mitochondrial factor be responsible for the absence of progressive necrosis?
We compared the myotoxic effect of chlorpromazine on mitochondria of gastrocnemius muscle in X-related muscular dystrophy (mdx) and control mice relative to changes in calmitine and calcium concentrations before and 3 and 6 days after a single injection of the drug. The results indicate that mdx mouse mitochondria are less sensitive to the myotoxic effect of chlorpromazine; calmitine and calcium binding were only slightly reduced compared to controls. Our observations indicate that the calmitine structure could differ in mdx and control mice with respect to calcium binding structures, and that the presence of calmitine in the mitochondria of mdx mouse skeletal muscle could explain why muscle degeneration does not occur in these animals. However, the muscles of patients with Duchenne muscular dystrophy (DMD) are lacking in calmitine and are subject to extensive progressive degeneration.
Lucas-Heron
B
B
Laboratoire de Physiologie, Faculté de Médecine, Nantes, France.
Schmitt
N
N
Ollivier
B
B
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002132:Calcium Radioisotopes; D002135:Calcium-Binding Proteins / Q000737:chemistry / Q000378:metabolism; D002155:Calsequestrin; D002746:Chlorpromazine / Q000633:toxicity; D004591:Electrophoresis, Polyacrylamide Gel; D006614:Hindlimb / Q000473:pathology; D051379:Mice; D008818:Mice, Neurologic Mutants; D008931:Mitochondria, Muscle / Q000187:drug effects / Q000378:metabolism*; D009124:Muscle Proteins / Q000737:chemistry / Q000378:metabolism; D009132:Muscles / Q000378:metabolism* / Q000473:pathology; D009137:Muscular Dystrophy, Animal / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009336:Necrosis; D012394:Rosaniline Dyes
D002132:Calcium Radioisotopes; D002135:Calcium-Binding Proteins; D002155:Calsequestrin; C503130:Casq1 protein, mouse; D009124:Muscle Proteins; D012394:Rosaniline Dyes; C004692:coomassie Brilliant Blue; D002118:Calcium; D002746:Chlorpromazine