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)

In support of the widely held belief that membrane defects are present in the muscular dystrophies, alterations have been found in some transport-related enzymes of cells from affected donors. Cell membranes were isolated from cultured dermal fibroblasts of victims of myotonic muscular dystrophy, and of Duchenne's muscular dystrophy, and from cells of normal age- and sex-matched donors. Myotonic cells had an elevated Na+, K+ ATPase. gamma-Glutamyl transpeptidase was elevated in Duchenne cells. Among all cells' 5'nucleotide phosphatase exhibited a remarkably constant specific activity.
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PMID:Transport enzymes in the cell membranes of cultured fibroblasts; alterations in dystrophic cells. 286 29

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

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

We have previously demonstrated, based on comparison of homologous amino acid sequences and of two-dimensional CNBr peptide gel patterns, that the myosin heavy chain in pectoralis muscles of Storrs, Connecticut dystrophic chickens is different from that of their normal controls (Huszar, G., Vigue, L., De-Lucia, J. Elzinga, M., and Haines, J. (1985) J. Biol. Chem. 260, 7429-7434). Others have shown, however, that genomic banks and mRNA complements of the control and dystrophic birds are not different. In the present studies, we have examined the hypothesis that the "dystrophic" myosin heavy chain is not a novel gene product, but is a developmental isozyme which is expressed in pectoralis muscles of adult chickens due to the dystrophic process. Two-dimensional maps of myosin heavy chain CNBr peptides were prepared from breast muscles of 17-day in ovo (embryonic), 25-day posthatch (neonatal), and adult birds of the Storrs dystrophic and of two control strains. Also, myosin and actomyosin ATPase enzymatic activities of the various preparations were determined in the pH range of 5.5 to 9.0. Analysis of the peptide maps demonstrates that the embyronic, neonatal, and control adult myosin heavy chain isozymes are distinctly different gene products with only minute variations between the respective developmental isozymes in dystrophic and control muscles. However, the pectoralis myosin heavy chain of adult dystrophic birds, which is a homogeneous isozyme population by amino acid sequences and gel patterns, corresponds to that of the neonatal-type myosin heavy chain. The ATPase properties of the embryonic, neonatal, or adult pectoralis myosins and actomyosins were not different, whether the level of specific activity or the pattern of pH activation is considered. Since the mobility of neonatal chicks (primarily neonatal-type isozymes) is not restricted, the differences in myosin heavy chain structures are part of the syndrome, but not the cause of avian muscular dystrophy.
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PMID:Myosin heavy chain in avian muscular dystrophy corresponds to the neonatal isozyme. 316 Jul 8

The cation-stimulated ATPase activities of erythrocyte membranes from patients with myotonic muscular dystrophy (MyD) were compared with the activities in age- and sex-matched controls. The enzymes included ouabain-sensitive ATPase, Mg2+-ATPase and Ca2+ + Mg2+-ATPase. Sampling and processing of the materials from patients with MyD and controls were simultaneously done in each experiment. The enzyme activities were varied with or without EGTA in the reaction medium, or with different temperatures for membrane storage, but no significant differences between MyD and control were observed in any conditions. The present study indicates no specific abnormality of the cation-stimulated ATPase activities of erythrocyte membranes in MyD.
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PMID:Erythrocyte membrane cation-stimulated ATPase activities in myotonic muscular dystrophy. 612 Feb 17

The activity of [Na+ + K+] Mg2+-ATPase of muscle surface membrane was investigated in 20 cases of the Duchenne type of progressive muscular dystrophy; it was found to be diminished and to have a changed reactivity to ouabain. There was nothing like it in cases of limb-girdle dystrophy and neurogenic muscular atrophies investigated for the purpose of comparisons, whereas in some cases of myotonic dystrophy and myotonia congenita the activity of the ATPase was indeed depressed, but the response to ouabain invariably remained normal.
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PMID:[Na+ + K+] Mg2+-ATPase of muscle plasma membranes in Duchenne muscular dystrophy. 625 58

TWO SODIUM TRANSPORT SYSTEMS HAVE BEEN ANALYZED IN THIS WORK: the voltage-sensitive sodium channel and the (Na(+), K(+)) ATPase pump. The sodium channel has been studied using a tritiated derivative of tetrodotoxin; the sodium pump has been studied using tritiated ouabain. Properties of interaction of tritiated tetrodotoxin and of tritiated ouabain with their respective receptors were observed in normal human skeletal muscle and in muscles of patients with myotonic muscular dystrophy and with lower motor neuron impairment. Levels of sodium pump and of sodium channels were measured at different stages of membrane purification. Microsomal fractions of normal human muscle have maximal binding capacities for tetrodotoxin of 230 fmol/mg of protein and of 7.4 pmol/mg of protein for ouabain. Dissociation constant for the complexes formed by the tetrodotoxin derivative and by ouabain with their respective receptors were 0.52 nM and 0.55 muM, respectively. In muscles from patients with myotonic muscular dystrophy, the maximal binding capacity for tetrodotoxin, i.e., the number of Na(+) channels was found to be very similar to that found for normal muscle. The maximal binding capacity for ouabain, i.e., the number of Na(+) pumps was three- to sixfold lower than in normal muscle. Dissociation constants for the complexes formed with the tetrodotoxin derivative and with ouabain were the same as for normal muscle. In muscles from patients with lower motor nerve impairment, the maximal binding capacities for tetrodotoxin and for ouabain were twice as high as in normal muscle. Again, dissociation constants for the complexes formed with the tetrodotoxin derivative and with ouabain were nearly unchanged as compared with normal muscle. These results suggest that sodium transport systems involved in the generation of action potentials and/or in the regulation of the resting potential are altered both in myotonic muscular dystrophy and in lower motor neuron impairment.
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PMID:Sodium channel and sodium pump in normal and pathological muscles from patients with myotonic muscular dystrophy and lower motor neuron impairment. 627 40

The ATPase activities and phosphoenzyme levels have been determined in sarcoplasmic reticulum (SR) membranes prepared from two animal models of muscular dystrophy, myodystrophic (myd/myd) and strain 129 dystrophic (129 dy/dy) mice. In both myd/myd and 129 dy/dy SR membranes, the basal ATPase activities are elevated above control levels, while the Ca-dependent ATPase activities are normal. The addition of 0.1% Triton X-100 not only lowers the basal ATPase activity of myodystrophic control SR membranes by 60%, but also lowers the elevated basal ATPase activity of myd/myd SR membranes to a similar level. The Ca-dependent ATPase activities of myodystrophic control and myd/myd SR membranes are increased approximately threefold by the addition of Triton. The addition of 0.1% Triton X-100 lowers the basal ATPase activities of 129 control and 129 dy/dy SR membranes to similar levels, but stimulates the CA-dependent ATPase activity of 129 dy/dy SR membranes to a level that is only 60% of that of 129 control SR membranes. The level of phosphoenzyme intermediate is decreased approximately 15% in myd/myd SR membranes and approximately 30% in 129 dy/dy SR membranes.
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PMID:Characterization of ATPase in sarcoplasmic reticulum from two strains of dystrophic mice. 644 33

The postnatal development of extrafusal fibers in the slow-twitch soleus muscle of genetically dystrophic C57BL/6J dy2J/dy2J mice and their normal age-matched controls was investigated by histochemical and quantitative methods at selected ages of 4, 8, 12, and 32 weeks. The majority of fibers in the soleus consisted of two kinds, fast-twitch oxidative-glycolytic (FOG) and slow-twitch oxidative (SO), according to reactions for alkaline-stable and acid-stable myosin ATPase and the oxidative enzyme, NADH-tetrazolium reductase. A minor population of fibers, stable for both alkaline- and acid-preincubated ATPase, but variable in staining intensity for NADH-TR, were designated "atypical" fibers. With age, the normal soleus exhibited a gradual increase in the number and proportion of SO fibers and a reciprocal, steady decline in the percentage of FOG fibers. Atypical fibers were numerous at 4 weeks, but were substantially diminished at later ages. Since total extrafusal fiber number remained relatively constant between the periods examined, this change in relative proportions reflects an adaptive transformation of fiber types characteristic of normal postnatal growth. A striking alteration in the number and distribution of fiber types was associated with the dystrophic soleus. At 4 weeks an 18% reduction in total fiber number was already noted. Subsequently, by 32 weeks a further 22% diminution in overall fiber number had occurred. With age, the absolute number and proportion of dystrophic SO fibers were drastically reduced. In contrast, the percentage of dystrophic FOG fibers increased significantly while their absolute numbers between 4 and 32 weeks remained relatively constant. Atypical fibers in the dystrophic solei were found in elevated numbers at all age groups, particularly at 12 weeks. They may, in part, represent attempts at regeneration or an intermediate stage in fiber-type transformation. Microscopically, both of the major fiber types appeared affected, albeit differently, by the dystrophic process. We suggest that a failure or retardation in the normal postnatal conversion of fiber types within the soleus muscle occurs in this murine model for muscular dystrophy.
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PMID:Abnormal distribution of fiber types in the slow-twitch soleus muscle of the C57BL/6J dy2J/dy2J dystrophic mouse during postnatal development. 665 Apr 41

Recent evidence suggests that cellular sodium regulation may be abnormal in muscular dystrophy. We have measured intracellular sodium concentration (Nai) in muscles of mdx mice (a model of Duchenne muscular dystrophy) using two techniques. Nai in isolated diaphragm (measured using a microelectrode) was 13.0 +/- 0.3 mM and 23.5 +/- 0.7 mM (mean +/- SE) in the control and mdx mice respectively. Nai in gastrocnemius muscle (calculated from extra- and intracellular volumes using serum and whole-muscle sodium concentrations) was 13 +/- 3 mM and 24 +/- 2 mM (mean +/- SE) in control and mdx, respectively. We argue that this abnormality in mdx tissues could reflect a reduced flux through the Na/K ATPase, although a contribution from increased Na leak cannot be ruled out. We also discuss possible consequences of an increased Nai: for example, raised Nai may lead to defective cell volume control in Duchenne dystrophy and the mdx mouse.
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PMID:Sodium is elevated in mdx muscles: ionic interactions in dystrophic cells. 843 2


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