A drug inhibits the mitochondrial protease inducing calmitine deficiency in skeletal muscle of patients with Duchenne's muscular dystrophy and dy/dy dystrophic mice.
This study demonstrates that the cause of calmitine deficiency in dy/dy dystrophic mice and patients with Duchenne's muscular dystrophy (DMD) is the same; i.e., the absence of an inhibitor of calmitine-specific mitochondrial protease. This inhibitor, which is present in control mice and control subjects, prevented degradation of the protein. It is also shown that a drug (IP96) was capable in vitro of inhibiting calmitine-specific mitochondrial protease from muscle of DMD patients and dy/dy mice. This drug was also active in vivo in an experimental model of myopathy created in the normal mouse by a single injection of chlorpromazine, a myotoxic drug, which induced temporary calmitine degradation. Thus, it seems quite likely that IP96 prevents calmitine degradation by inhibiting the specific protease.
Lucas-Heron
B
B
Groupe de Recherche sur les myopathies, Laboratoire de Physiologie, UER de Médecine, Nantes, France.
D000818:Animals; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002155:Calsequestrin / Q000172:deficiency*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008931:Mitochondria, Muscle / Q000187:drug effects / Q000201:enzymology*; D024101:Mitochondrial Proteins; D018482:Muscle, Skeletal / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D009136:Muscular Dystrophies / Q000201:enzymology* / Q000378:metabolism; D009137:Muscular Dystrophy, Animal / Q000201:enzymology* / Q000378:metabolism; D011480:Protease Inhibitors / Q000494:pharmacology*
C503129:CASQ1 protein, human; D002135:Calcium-Binding Proteins; D002155:Calsequestrin; C503130:Casq1 protein, mouse; D024101:Mitochondrial Proteins; D011480:Protease Inhibitors