Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026850 (muscular dystrophy)
 5,870 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ca2+-uptake activities of the sarcoplasmic reticulum (SR) were determined with a Ca2+-sensitive electrode in homogenates from fast- and slow-twitch muscles from both normal and dystrophic mice (C57BL/6J strain) of different ages. Immunochemical quantification of tissue Ca2+-ATPase content allowed determination of the specific Ca2+-transport activity of the enzyme. In 3-week-old mice of the dystrophic strain specific Ca2+ transport was already significantly lower than in the normal strain. It progressively decreased with maturation and reached only 40-50% and 30-50% of the normal values in fast- and slow-twitch muscles of adult dystrophic animals, respectively. Tissue contents of calsequestrin were reduced in both types of muscle leading to an increased Ca2+-ATPase to calsequestrin protein ratio. Equal amounts of the Ca2+-ATPase protein (detected by Coomassie blue staining of polyacrylamide gels) were present in SR vesicles isolated by Ca2+-oxalate loading from adult normal and dystrophic fast-twitch muscles. However, the specific ATP-hydrolysing activity of the enzyme was approximately 50% lower in dystrophic than in normal SR. The reduced ATP-hydrolysing activity was correlated with decreased Ca2+-transport activity, phosphoprotein formation and fluorescein isothiocyanate labeling as determined in total microsomal and heavy SR fractions. Although the Ca2+ and ATP affinities of the enzyme were unaltered, its ATPase activity was reduced at all levels of ATP in the dystrophic SR. Taken together, these findings point to a markedly impaired function of the SR and an increase in the population of inactive SR Ca2+-ATPase molecules in murine muscular dystrophy.
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PMID:Postnatal development of Ca2+-sequestration by the sarcoplasmic reticulum of fast and slow muscles in normal and dystrophic mice. 296 44

Alpha-Sarcoglycan is a glycoprotein associated with the dystrophin complex at sarcolemma of skeletal and cardiac muscles. Gene defects in alpha-sarcoglycan lead to a severe muscular dystrophy whose molecular mechanisms are not yet clear. A first insight into the function of alpha-sarcoglycan was obtained by finding that it is an ATP-binding protein and that it probably confers ability to hydrolyse ATP to the purified dystrophin complex [Betto, Senter, Ceoldo, Tarricone, Biral and Salviati (1999) J. Biol. Chem. 274, 7907-7912]. In the present study, we present definitive evidence showing that alpha-sarcoglycan is an ATP-hydrolysing enzyme. The appearance of alpha-sarcoglycan protein expression was correlated with the increase in ecto-nucleotidase activity during differentiation of C2C12 cells. Approx. 25% of ecto-nucleotidase activity displayed by the C2C12 myotubes was inhibited by preincubating cells with an antibody specific for the ATP-binding motif of alpha-sarcoglycan. This demonstrates that alpha-sarcoglycan substantially contributes to total ecto-nucleotidase activity of C2C12 myotubes. To characterize further this activity, human embryonic kidney 293 cells were transfected with expression plasmids containing alpha-sarcoglycan cDNA. Transfected cells exhibited a significant increase in the ATP-hydrolysing activity that was abolished by the anti-alpha-sarcoglycan antibody. The enzyme had a substrate specificity for ATP and ADP, did not hydrolyse other triphosphonucleosides, and the affinity for ATP was in the low mM range. The ATPase activity strictly required the presence of both Mg2+ and Ca2+ and was completely inhibited by suramin and reactive blue-2. These results show that alpha-sarcoglycan is a Ca2+, Mg2+-ecto-ATPDase. The possible consequences of the absence of alpha-sarcoglycan activity in the pathogenesis of muscular dystrophy are discussed.
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PMID:Characterization of the ATP-hydrolysing activity of alpha-sarcoglycan. 1503 52