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Query: UMLS:C0026850 (muscular dystrophy)
 5,870 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A comparative study was carried out in the properties of ATPase system of the skeletal muscle nuclei in the rabbits in norm and with experimental muscular dystrophy conditioned by E-avitaminosis. It is shown that in the system, containing 1.5 mM of MgCl2, ATPase system of the nuclei is activated by sodium and potassium ions. In norm maximum activation is observed with their presence in the medium, the concentration being 80 and 70 mM, respectively. With experimental muscular dystrophy maximum activating concentrations decrease and are equal for both cations - 30 mM. Activation of the enzymatic system by these ions is specific because the introduction of equimolar quantities of cholin-chloride or lithium, cesium ions instead of sodium ions into the incubation medium evokes no activation of the ATPase system of the rabbit skeletal muscles both in norm and with experimental muscular dystrophy. A simultaneous presence of sodium and potassium ions in optimum concentrations in the incubation medium makes for an increase of ATPase activity to the same extent as the presence of one of these cations. Oubain, a specific inhibitor of Mg2+, Na+, K+- ATPase, taken in the concentrations of 10(-4) and 10(-3) M did not decrease the intensity of ATP hydrolysis and its activation conditioned by the presence of sodium or potassium. A conclusion is made that Mg2+, Na+, K+-ATPase taking part in the work of "sodium pump" is absent in the nuclei of skeletal muscles.
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PMID:[Availability of Mg2+, Na+, and K+-ATPase in the nuclei of the skeletal muscles of rabbits normally and during experimental muscular dystrophy]. 12 69

The total ATPase activity of the rabbit skeletal muscle nuclei was established to be a sum of activities of two ATPases--Mg2+ and Mg2+, Ca2+-ATPases. The latter composes 50% of total ATPase activity for skeletal muscles nuclei of the normal rabbits and 30% for skeletal muscles nuclei of the rabbits with muscular dystrophy. Mg+, Ca2+-ATPase of the skeletal muscle nuclei is activated by calcium ions within a range of 10(-6)--10(-4) M and is inhibited with its concentration of 0.5-10(-3) M and higher. Sodium and potassium ions activate Mg2+, Ca2+-ATPase. Inhibition of Mg2+-ATPase is observed for the skeletal muscle nuclei of the rabbits in norm with the presence of 80 mM of Na+ and 70 mM of K+ in the incubation medium. Under experimental muscular dystrophy such an effect is not observed in connection with the fact that the concentration of monovalent cations in the incubation medium does not exceed 60 mM. The ATPase activity in nuclei of the rabbit skeletal muscles may be also manifested in the presence of Mn2+ greater than Ca2+ greater than Ba2+. A problem is under discussion as to substitution of ions Mg2+ by ions Mn2+, Ca2+, Ba2+ in manifestation of the Mg2+ATPase activity for the skeletal muscle nuclei of the normal rabbits and of those with experimental dystrophy.
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PMID:[Mg 2+, Ca 2+-ATPase of skeletal muscle nuclei in normal rabbits and in rabbits with experimental muscular dystrophy]. 12 61

The level of the ATPase activity in the skeletal muscles nuclei with experimental muscular dystrophy and the sensitivity to bivalent (Mg2+, Ca2+) and univalent (Na+, K+) cations under conditions of delipidation were studied. It is established that among ATPases of the young rabbit skeletal muscles nuclei there is ATPase sensitive to monovalent cations: the presence of Na+ or K+ produces a 45% increase in its activity in some experiments as compared to the initial level. This activation is attributed to Mg2+, Ca2+-ATPase the action of which is not realized in the presence of EGTA-chelator of calcium ions. A decrease in the total ATPase activity in the skeletal muscles nuclei resulted from the experimental muscular dystrophy development occurs due to a decrease in the Mg2+, Ca2+-ATPase activity as the ability for activation by the monovalent cations is practically lost under these conditions. Delipidation of the skeletal muscles nuclei, which results in their loss of some phospholipids and cholesterin, is accompanied by the ATPase activity decrease. At the same time the nuclei ATPase activity lose its ability to activate by monovalent cations: Na+, K+. A conclusion is made that during delipidation the decrease in the total ATPase activity is due to a decrease in the activity of its Mg2+, Ca2+-part.
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PMID:[Changes in the ATP-ase activity of skeletal muscle nuclei of rabbits with dystrophy and following their delipidation]. 13 32

The properties and localization of ATPase system in nuclei of skeletal muscle of normal rabbit and of those with experimental muscle dystrophy were studied by electron cytochemistry. The product of cytochemical reaction of ATP hydrolysis, which is a marker of ATPase activity localization in nuclear ultrastructures, was detected on the nuclear membrane, in chromatin and in the nucleolus, ATPase activity in the nuclei was detected in the presence of both, Mg2+ and Ca2+. Addition to the incubation medium, originally containing Mg2+, Na+ and K+, resulted in an increased formation of the product reaction in all the nuclear ultrastructures in both in the norm and under experimental muscle dystrophy. However, specific inhibitor of Mg2+, Na+, K+-ATPase--ouabain--suggests the absence in the nuclei of skeletal muscles of rabbit of transport ATPase working in the "Na-pump" system. The results of experiments with a specific complex of Ca2+--EGTA allow to suppose that Mg2+, Ca2+-ATPase of skeletal muscle nuclei of normal rabbits is localized in the nucleoplasm, whereas Mg2+-ATPase is found on the nuclear membrane. Using EGTA we failed to detected the localization of Mg2+, Ca2+-ATPase in nuclear ultrastructures upon experimental muscular dystrophy.
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PMID:[Electron-cytochemical study of the localization and properties of ATPases in the isolated nuclei of rabbit skeletal muscle under normal conditions and in experimental muscular dystrophy]. 14 28

The purpose of this study was to determine whether the previously reported differences in adenylate cyclase activity between the sarcolemma of normal and dystrophic chick muscles are also found in the SR, to search for a possible relationship between the adenylate cyclase changes and the pathophysiology of dystrophy, and to investigate whether the findings can be extended to Duchenne human muscular dystrophy by studying the adenylate cyclase and ATPase activities of erythrocyte ghosts from DMD patients and carriers. Microsomes were separated by standard techniques from the pectoralis muscles of normal and dystrophic ckeckens of various ages. The microsomal yields were significantly larger in dystrophic muscles. Adenylate cyclase activities in dystrophic microsomes were higher than those in matched controls and increased with the progression of the disease. The ratio between the two rose from one at 2 weeks of age to nine at about 9--10 weeks. Kinetic analyses showed that the ks for MgATP2- was about 40 microM (at 3 mM Mg2+ and 0.3 mM Ca2+) both in normal and dystrophic microsomes, that calcium caused umcompetitive inhibition of the enzyme (Ki = 0.2 mM), that the effect of calcium was noncooperative (Hill coefficient, nH = 1), that calcium did not affect the cooperativity for MgATP2-, and that magnesium competitively removed the calcium inhibition and caused additional, cooperative stimulation of the enzymatic activity (ka = 1.5 mM; NH =2). The major difference between normal and dystrophic adenylate cyclase was a higher enzymatic velocity in the latter, suggesting a larger amount of enzyme. We investigated whether altered cAMP levels may effect calcium accumulation. Calcium uptake measured (in the presence of oxalate) at several ages revealed no difference between normal and dystrophic chickens. The extent of calcium binding was also similar, although the kd for Ca2+ was lower in dystrophic microsomes. Binding was enhanced in the presence of exogenous protein kinase, but the responses of normal and dystrophic tissues were similar. We concluded that the elevation of adenylate cyclase in dystrophy was not related to microsomal calcium accumultion. Ivestigation of the localization of microsomal adenylate cyclase supported this view. Separation of calcium-loaded microsomes on a discontinuous sucrose gradient into four fractions demonstrated that adenylate cyclase activity, measured in the presence of Lubrol-PX and EGTA, was inversely related to calcium-accumulating activity. Na+, K+-ATPase comigrated with adenylate cyclase. Highest specific activities were found in the lightest fraction. These observations were confirmed by histochemical studies. The reaction product from adenylate cyclase activity was present predominantly in the terminal cisternae of the SR. In the context of the literature, our findings suggest that the rises in adenylate cyclase and Na+, K+-ATPase in avian dystrophy are compensatory changes, elicited by a defect in ECC at the calcium release step...
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PMID:Adenylate cyclase in muscular dystrophy. 15 10

Skeletal muscles from healthy dogs and Labrador Retrievers with hereditary muscular dystrophy were examined morphologically and histochemically and were analyzed biochemically for Na+, K+, Ca2+, Mg2+, Zn2+, Cu2+, Cl-, total muscle water, and total neutral lipid content. Flame atomic absorption spectrophotometer was used for elemental quantitation of hydrochloric acid tissue extracts. Muscle samples from dystrophic dogs contained substantially increased concentrations of Na+, Ca2+, Zn2+, Cu2+, and Cl-, and a considerable reduction in the content of K+ and Mg2+ compared with samples from healthy dogs. Total muscle water and total fat content was higher in muscles from dystrophic dogs. Most muscle samples from dystrophic dogs had a type-2 fiber deficiency and an increase in number of fibers with internalized nuclei.
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PMID:Analysis of muscle elements, water, and total lipids from healthy dogs and Labrador retrievers with hereditary muscular dystrophy. 272 11

Combined histochemical and biochemical studies have shown, that the histochemical activity of mitochondrial Mg2+-activated ATPase closely correlates with the coupling state of oxidative phosphorylation (Meijer and Vloedman 1980). Using this histochemical method 646 unselected skeletal muscle biopsies have been investigated. Activation of the enzyme, i.e. loosely coupled mitochondria were present either focally or diffusely expressed in 28% of the biopsies irrespective of the underlying disorder. Most often it was found in mitochondrial myopathies and in progressive muscular dystrophy type Duchenne; in a lesser degree it was also present in neurogenic atrophy and in various other disorders. Ninety two percent of all cases with loose coupling showed mitochondrial proliferations. On the other hand in 20% of all cases with mitochondrial proliferations including 19 cases of diffuse mitochondrial myopathy and 3 of progressive external ophthalmoplegia no activation of the enzyme was found. The results show that loose coupling is closely but not absolutely associated with mitochondrial proliferation, it is present in mitochondrial myopathies but also in various other muscular disorders with different pathogenesis.
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PMID:Activation of mitochondrial ATPase as evidence of loosely coupled oxidative phosphorylation in various skeletal muscle disorders. A histochemical fine-structural study. 294 45

The effect of loop diuretics at concentrations known to influence cellular water entry coupled to Na-K-Cl co-transport, upon the vacuolation and detubulation following osmotic shock, was investigated in amphibian skeletal muscles. These were exposed to a glycerol-Ringer solution (18 min), an isotonic Ca2+/Mg2+ Ringer solution and cooling. Adding bumetanide (1.0 and 2.0 microM) to these solutions sharply reduced the incidence of detubulation, assessed by abolition or otherwise of action potential after-depolarisations, from 93.9 +/- 4.7% (n = 6) to 5.0 +/- 1.1% (n = 4: mean +/- SEM: 2.0 microM bumetanide). It dramatically reduced the number and fraction of muscle volume occupied by tubular vacuoles, measured using confocal microscopy, from 60.3 +/- 4.3% (n = 10) to 9.0 +/- 1.1% (n = 35). The incidence of large horseradish peroxidase-lined tubular vacuoles, viewed using electronmicroscopy, similarly was reduced with 2 microM bumetanide in the glycerol-Ringer solution. Bumetanide acted through cellular volume adjustments early in the detubulation protocol. Thus, it exerted its maximum effect when added to the glycerol-Ringer, rather than the Ca2+/Mg2+ Ringer solution. Furthermore, whereas fibre diameters measured using scanning electron microscopy returned to normal during glycerol treatment relative to those of control fibres left in isotonic Ringer, addition of 2.0 microM bumetanide in the glycerol Ringer left markedly smaller fibre diameters. Finally equipotent concentrations of the chemically distinct loop diuretics. furosemide and ethacrynic acid similarly influenced detubulation. These findings implicate Na-K-Cl co-transport in the water entry into muscle fibres that would be expected following introduction of extracellular glycerol. This might then enable the subsequent Na-K-ATPase dependent water extrusion that produces the tubular distension (vacuolation) and detachment (detubulation) following glycerol withdrawal, phenomena also observed in muscular dystrophy.
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PMID:Loop diuretics inhibit detubulation and vacuolation in amphibian muscle fibres exposed to osmotic shock. 1081 37

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