Elevated calmodulin levels and reduced calmodulin-stimulated calcium-ATPase in Duchenne progressive muscular dystrophy.
We determined the calmodulin concentration and Ca2+-ATPase activity in subcellular fractions recovered from samples of vastus lateralis muscle obtained from 18 patients with Duchenne muscular dystrophy, 10 patients with other primary myopathies, 5 with spinal muscular atrophy, and 16 age-matched controls. Calmodulin levels were increased in the cytosol, plasmalemma, and heavy sarcoplasmic reticulum fractions from Duchenne dystrophy patients; the greatest increases occurred at early stages of disease or in mildly progressive cases. The total Ca2+-ATPase activities were decreased in the Duchenne dystrophy muscles; calmodulin caused a minimal stimulation of the activity in calmodulin-depleted membranes from Duchenne dystrophy compared with control membranes. The changes in calmodulin concentration and Ca2+-ATPase activity complement previous observations of reduced calsequestrin and dystrophin concentrations in Duchenne dystrophy muscles and suggest that these muscles lose calcium regulatory functions at early stages of the disease process.
Niebroj-Dobosz
I
I
Akademia Medyczna w Warsawie-Klinika Neurolgiczna, Poland.
Kornguth
S
S
Schutta
H S
HS
Siegel
F L
FL
D000251:Adenosine Triphosphatases / Q000378:metabolism*; D002118:Calcium / Q000502:physiology*; D002147:Calmodulin / Q000378:metabolism* / Q000494:pharmacology; D002648:Child; D002675:Child, Preschool; D006801:Humans; D009132:Muscles / Q000378:metabolism / Q000648:ultrastructure; D009134:Muscular Atrophy, Spinal / Q000378:metabolism; D009135:Muscular Diseases / Q000378:metabolism; D009136:Muscular Dystrophies / Q000378:metabolism*; D013347:Subcellular Fractions / Q000378:metabolism
D002147:Calmodulin; D000251:Adenosine Triphosphatases; D002118:Calcium