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)

A fraction of erythrocyte Band 3 (Mr, 93,000) glycoprotein that demonstrates decreased autophosphorylation in membranes from myotonic muscular dystrophy patients is demonstrated. Sequential affinity chromatography of Triton X-100 solubilized erythrocyte membrane proteins separated three specifically retained glycoprotein fractions on a Ricin Communis I-Sepharose 4B column. One fraction contains a portion of the major sialoglycoprotein (apparent Mr, 78,000) and is specifically eluted from the column by 10 mM NaCl and 100 mM D-galactose (10/100). The two other glycoprotein fractions are eluted by 100 mM NaCl, 10 mM D-galactose (100/10) and 100 mM NaCl, 100 mM D-galactose (100/100). The composition of both fractions contains greater than 95% Band 3 (apparent Mr, 93,000 glycoprotein. The quantities of glycoprotein in each fraction obtained from erythrocytes of myotonic dystrophy patients did not differ from the quantities obtained from control erythrocytes. Following endogenous protein kinase incubations of ghosts with [gamma-32P]ATP, the specific [32P] phosphorylation of the 10/100 and 100/10 fractions are identical. The 100/100 fraction, which makes up approximately 3% of the total erythrocyte membrane protein, demonstrates a different pattern for myotonic dystrophy patients; specific phosphorylation was reduced by 50% relative to activity in control experiments. These findings are consistent with previous experiments that demonstrated decreased autophosphorylation of the glycoprotein portion of Band 3 (Roses & Appel, 1975, J. Membrane Biol 20:51) and are consistent with the autosomal dominant mode of inheritance in this disease.
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PMID:Isolation of an abnormally phosphorylated erythrocyte membrane band 3 glycoprotein from patients with myotonic muscular dystrophy. 44 24

We applied a simple lead salt-based stain for interstitial and vascular 5'-nucleotidase to 150 muscle biopsy specimens. No reaction was obtained with 2'- or 3'-adenosine monophosphate, indicating that the stain was specific, and distinct from phosphatases. Staining was not inhibited by alpha, beta-methylene adenosine 5'-diphosphate, but was prevented by formaldehyde fixation or by brief immersion in octoxynol 9 (Triton X-100). Nucleotidase stains the following specific histologic sites that distinguish it from alkaline phosphatase: the intima and adventitia of medium-sized and large arteries, perineural and muscle spindle sheaths, and tendon insertions. Aside from these structures, normal muscle shows little reaction, as the sarcoplasm and sarcolemma do not stain. Neither of these enzymes shows a compensatory increase, histochemically, in myo-adenylate deaminase deficiency. In Duchenne's muscular dystrophy, however, and particularly in inflammatory myopathy, interstitial staining of 5'-nucleotidase is increased, leading to investment of most muscle fibers in the affected area. The stain rarely identifies regenerating fibers. Although alkaline phosphatase commonly shows a corresponding increase in interstitial staining, we encountered six cases of inflammatory myopathy in which this was absent, despite pronounced endomysial staining in the 5'-nucleotidase reaction. 5'-Nucleotidase thus appears to provide a valuable adjunct in the diagnosis of inflammatory myopathy.
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PMID:Interstitial 5'-nucleotidase stain for frozen biopsy specimens of skeletal muscle. A useful adjunct in the diagnosis of polymyositis. 619 1

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

We have previously reported a decreased activity of the lysosomal enzyme dipeptidyl aminopeptidase-I (DAP-I) in cultured fibroblasts from patients with Duchenne's muscular dystrophy (DMD). Here we report that electron microscope examination of these cells reveals the presence of abundant lamellar bodies, a morphologic abnormalities commonly associated with impaired lysosomal function. Morphometric analysis of these cytoplasmic figures in dystrophic cells shows a sevenfold increase relative to normal controls (P less than 0.01). Analysis of lysosomal density profiles by density gradient centrifugation reveals similar patterns in normal and DMD cells. Treatment of lysosomes wit the nonionic detergent Triton X-100 causes an activation of DAP-I. This activation, attributable to structure-linked latency, is markedly diminished in DMD cells which show an optimal activation of only 180% compared to 255% for control fibroblasts (P less than 0.01). These data suggest an alteration in the properties of the lysosomal membrane in DMD fibroblasts. This suggestion is also supported by studies on the release of DAP-I from lysosomes by osmotic shock which show it to be a membrane-associated enzyme with membrane-binding characteristics intermediate between those of tightly bound beta-glucosidase and those of unbound N-acetylgalactosaminidase. The latency characteristics of these other lysosomal enzymes are not altered in the DMD cells, indicating that the effect is specific for DAP-I.
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PMID:Structural changes in lysosomes from cultured human fibroblasts in Duchenne's muscular dystrophy. 678 12

The response of the membrane-bound enzyme AChE to changes in temperatures was investigated to test the applicability of the "generalized membrane defect" hypothesis proposed for human myotonic and Duchenne muscular dystrophies to the two forms of muscular dystrophy expressed in mice. For intact platelets from homozygous normal and dystrophic mice of both strains, a break (Tc) occurred in the Arrhenius plot of AChE activity at approximately 22 C. Solubilization of membrane-bound AChE by Triton X-100 produced a nonlinear Arrhenius plot over the temperature range (7.7 C to 37 C) in normal and dystrophic mice of both strains. However, in the presence of phospholipase A2 + C and Triton X-100, a linear Arrhenius plot was produced indicating that the membrane-bound enzyme is normally modulated by a bulk lipid domain as well as by a tightly bound (immobilized) phospholipid domain. The temperature response of platelet AChE from normal and dystrophic mice of both strains was not significantly different. These results showing normal temperature kinetics of AChE do not lend support to the theory of a membrane defect in the platelets of dystrophic mice.
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PMID:Evidence against a generalized membrane defect in dystrophic mice platelets. 712 7

Normal and dystrophic mouse muscles were separated into a predominantly white muscle fraction (gastrocnemius, extensor digitorum longus) and a predominantly red muscle fraction (diaphragm). Acetylcholinesterase (AChE) was extracted from each muscle fraction using a Triton X-100/NaCl buffer. Six forms of AChE were separated from each muscle homogenate by velocity sedimentation on linear sucrose gradients. Their apparent sedimentation coefficients in each case were 19.7S, 16.0S, 13.3S, 10.4S, 7.6S, and 3.9S. Gel electrophoresis of crude muscle homogenates under nondenaturing conditions (native gels) and of ech separate isozyme fraction gave one band of AChE activity with a consistent Rf (relative mobility) value. Reelectrophoresis of native gel bands on SDS/acrylamide slab gels revealed a similar monomeric subunit protein from either crude muscle homogenates or isozyme fractions with an apparent molecular weight of approximately 69,000 daltons. Our results indicate that the AChE distribution and activity are severely affected in dystrophic "white" muscles (anaerobic) but much less so in "red" muscles (aerobic). Dystrophic predominantly white muscles weigh less, contain less protein, and have a decreased total AChE activity in comparison with their normal counterparts. Furthermore, the relative proportions of AChE activity in each isozyme fraction is altered between normal white and dystrophic white muscle fractions: i.e., dystrophic white muscle contains a decreased proportion of a low molecular weight form (7.6S) and increased proportions of higher molecular weight forms (16.0S, 19.7S). In contrast, no significant differences occur in AChE activity or distribution between normal and dystrophic predominantly red muscle. The changes in white muscle AChE are toward a pattern common to red muscle. This suggests that the effect of muscular dystrophy and its related stress on mouse white muscle is at least in part a shift from a predominantly anaerobic, fatigable metabolism to an aerobic, fatigue-resistant metabolism.
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PMID:Altered acetylcholinesterase isozyme patterns in mice with hereditary muscular dystrophy. 724 Oct 63

The aim of the present study was to investigate the direct effects of a reactive oxygen species, H(2)O(2), on the contractile function and sarcoplasmic reticulum properties of dystrophin-deficient diaphragm using chemically skinned fibers and sarcoplasmic reticulum vesicle preparations. The results obtained using Triton X-100-skinned fibers demonstrate that exposure to 1 mM H(2)O(2) had similar effects on the maximal Ca(2+)-activated tension and on the Ca(2+) sensitivity of the contractile apparatus of diaphragm fibers in Bl10 and mdx mice. The effects of H(2)O(2) were also assessed on sarcoplasmic reticulum function using saponin-skinned fibers and sarcoplasmic reticulum vesicle preparations. We found that H(2)O(2) induced changes in sarcoplasmic reticulum properties, particularly in the Ca(2+) pump function. The most important finding was that diaphragm muscle from mdx mice displayed increased sensitivity to the oxidant. Furthermore, in isolated superfused diaphragm muscle from mdx mice, the data demonstrate that the amount of superoxide anion produced under fatiguing conditions was increased. Our study shows that the sarcoplasmic reticulum, and the Ca(2+) pump in particular, in dystrophin-deficient muscles display increased susceptibility to H(2)O(2) injuries. This suggests that free radicals might, therefore, be involved in the pathophysiological pathway and dysregulation of Ca(2+) homeostasis of muscular dystrophy.
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PMID:Greater susceptibility of the sarcoplasmic reticulum to H2O2 injuries in diaphragm muscle from mdx mice. 1680 56

The laminin-alpha2 chain, referred to as merosin, forms part of the laminin-2 heterotrimer (alpha2beta1gamma1), which is principally expressed in the basement membrane of muscle. Nearly half of patients suffering from congenital muscular dystrophy (CMD) have abnormalities in the laminin-alpha2 chain (LAMA2) gene, and the merosin-deficient Lama2dy mouse shows CMD. The expression of merosin in thymus, the abnormalities in the gland of Lama2dy mice, and the presence of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) in thymus prompted us to study the possible effects of the deficiency of merosin on thymus BuChE. We found that, while AChE activity decreased by approximately 50% in merosin-deficient thymus, the deficiency had little effect on BuChE activity. About 65% of thymus BuChE activity was extracted with a saline buffer and 30% with 1% Triton X-100. Sedimentation analyses and phenyl-agarose chromatography showed that thymus contained amphiphilic BuChE monomers (G(1)(A),44%) and dimers (G(2)(A),33%), and hydrophilic tetramers (G(4)(H),23%). Binding assays with various plant lectins revealed differences between the oligoglycans linked to BuChE tetramers and lighter components. The deficiency of merosin had no effect on the biosynthesis of thymus BuChE as judged by the lack of major changes between control and Lama2dy mice thymuses in the distribution of BuChE molecules and the level of lectin binding. The detoxifying action of BuChE, its role as a backup to AChE, and the relevance of the cholinergic dialogue between T cells and stromal cells for T lymphocyte proliferation, maturation and survival support a physiological function for BuChE in thymus.
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PMID:Butyrylcholinesterase activity and molecular components in thymus of healthy and merosin-deficient Lama2dy mice. 1717 75

The activities and the molecular forms of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) were examined in 28 biopsies of quadriceps femoris muscle from children with a myopathic non-dystrophic disease. These cases were compared with biopsies from 7 children with a neurogenic damage, 14 children with muscular dystrophy and 12 controls. All the biopsies, histochemically stained for AChE, showed no endplates; electron microscopy of muscle fibers from diseased biopsies revealed a diffuse AChE reaction on the fiber surfaces which was not associated with any endplate structure. The AChE activities in NaCl/Triton X-100 extracts from the three groups of patients were all more or less the same, and average levels were similar to those evidenced in controls. The complete disappearance of heavy and medium forms of AChE was noted in 60% of myopathic non-dystrophic patients. We never observed the pattern characteristic to these patients in the biopsies from neurogenic and dystrophic patients or from controls, which displayed a high variability in the profiles of AChE molecular forms.
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PMID:Muscle acetylcholinesterase in childhood myopathies. 2049 22

Murine muscular dystrophy is characterized by a reduction of the 10S molecular form of acetylcholinesterase (AChE); this reduction occurs in both strains of dystrophic mice and at the time of the phenotypic appearance of the disease. In the present study we have analyzed the biochemical features, the cellular distribution and the developmental appearance of the AChE alteration. Sequential extractions with low salt, detergent and high salt revealed that this alteration affects only membrane-bound forms (those requiring Triton X-100 for solubilization), while both the low salt soluble and the high salt soluble forms appeared almost identical in normal and dystrophic muscles. Specific activity, sensitivity to different ions, pH dependence and Km were found to be identical in the enzymes from normal and dystrophic muscles, suggesting that the catalytic site of the 10S form is probably not altered. Further analysis, by non-denaturing gel electrophoresis, of the detergent soluble forms separated by sedimentation, revealed a single band for the 4S, a doublet for the 6S and three bands for the 10S peaks, indicating the existence of charge heterogeneity in AChE molecular forms. The corresponding molecular forms from dystrophic muscles behaved identically upon electrophoresis: the residual activity in the detergent soluble 10S form could still be separated into three bands, comigrating with their normal counterparts. Neuraminidase treatment resulted in a reduction of migration of both the 6S and 10S derived bands, but not of the 4S species, showing that sialic acid is added only to polymeric forms. Interestingly, the reduction of the 10S form appears to be linked to a developmental stage not reached in cell cultures, as cultured myotubes from muscles of dystrophic mice contained normal amounts of membrane-bound AChE forms. The molecular mechanism underlying the reduction of the tetrameric membrane bound AChE form in dystrophic muscle and the possible functional consequences are discussed.
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PMID:Membrane acetylcholinesterase in murine muscular dystrophy In vivo and in cultured myotubes. 2487 58


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