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 number of active oxygen species are likely implicated in the etiology or manifestation of several pathological conditions, including aging, arthritis, carcinogenesis, atherosclerosis, and muscular dystrophy. Ascorbate plays a key role in protecting cells against oxidative damage. Paradoxically, in the presence of Fe3+ or Cu2+, ascorbate can promote the generation of the same reactive oxygen species (.OH, O2-, H2O2, and ferryl ion) it is known to destroy. This prooxidant activity derives from the ability of ascorbate to reduce Fe3+ or Cu2+ to Fe2+ or Cu+, respectively, and to reduce O2 to O2-. and H2O2. Damage to nucleic acid and proteins results from the binding of either Fe2+ or Cu+ to metal binding sites on these macromolecules followed by reaction of the metal complexes with H2O2; this leads to the production of active oxygen species that attack functional groups at or near the metal binding sites.
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PMID:Ascorbic acid and oxidative inactivation of proteins. 196 58

In the presence of O2, Fe(III) or Cu(II), and an appropriate electron donor, a number of enzymic and nonenzymic oxygen free radical-generating systems are able to catalyze the oxidative modification of proteins. Whereas random, global modification of many different amino acid residues and extensive fragmentation occurs when proteins are exposed to oxygen radicals produced by high energy radiation, only one or a few amino acid residues are modified and relatively little peptide bond cleavage occurs when proteins are exposed to metal-catalyzed oxidation (MCO) systems. The available evidence indicates that the MCO systems catalyze the reduction of Fe(III) to Fe(II) and of O2 to H2O2 and that these products react at metal-binding sites on the protein to produce active oxygen (free radical?) species (viz; OH, ferryl ion) which attack the side chains of amino acid residues at the metal-binding site. Among other modifications, carbonyl derivatives of some amino acid residues are formed; prolyl and arginyl residues are converted to glutamylsemialdehyde residues, lysyl residues are likely converted to 2-amino-adipylsemialdehyde residues; histidyl residues are converted to asparagine and/or aspartyl residues; prolyl residues are converted to glutamyl or pyroglutamyl residues; methionyl residues are converted to methionylsulfoxide residues; and cysteinyl residues to mixed-disulfide derivatives. The biological significance of these metal ion-catalyzed reactions is highlighted by the demonstration: (i) that oxidative modification of proteins "marks" them for degradation by most common proteases and especially by the cytosolic multicatalytic proteinase from mammalian cells; (ii) protein oxidation contributes substantially to the intracellular pool of catalytically inactive and less active, thermolabile forms of enzymes which accumulate in cells during aging, oxidative stress, and in various pathological states, including premature aging diseases (progeria, Werner's syndrome), muscular dystrophy, rheumatoid arthritis, cataractogenesis, chronic alcohol toxicity, pulmonary emphysema, and during tissue injury provoked by ischemia-reperfusion. Furthermore, the metal ion-catalyzed protein oxidation is the basis of biological mechanisms for regulating changes in enzyme levels in response to shifts from anaerobic to aerobic metabolism, and probably from one nutritional state to another. It is also involved in the killing of bacteria by neutrophils and in the loss of neutrophil function following repeated cycles of respiratory burst activity.
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PMID:Metal ion-catalyzed oxidation of proteins: biochemical mechanism and biological consequences. 228 87

In order to understand the pathogenesis of mouse muscular dystrophy, we investigated the levels of the thiobarbituric acid-reactive substances (TBARS), H2O2 and NADPH oxidase activity, which were relative to the acceleration of oxidative conditions, in tongue and hindleg skeletal muscles from C57BL/6J-dy mice. The TBARS content (702 nmol/g protein) in skeletal muscles from 2-months-old dystrophic mice was increased significantly over that (384 nmol/g protein) in muscles from age-matched normal mice. The H2O2 concentration in dystrophic skeletal muscles was 30% higher than that in normal ones. Microsomal NADPH oxidase activity which was related to the production of superoxide anions, was similar between dystrophic muscles (4.66 nmol/10 min/mg protein) and normal muscles (4.11 nmol/10 min/mg protein). These results indicate that oxidation is accelerated in the dystrophic muscles. However, the TBARS content in the tongues of dystrophic mice was identical to that of normal mice. This finding supports our bone-muscle growth imbalance hypothesis for the pathogenesis of mouse muscular dystrophy.
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PMID:Elevation of the level of thiobarbituric acid-reactive products in hindleg skeletal muscle of dystrophic mice, but non-elevation in tongue muscle. 822 42

Muscular dystrophy is a genetic disease that affects primarily skeletal muscle. The dystrophin absence has been related to the degeneration of muscle fibres. Indirect evidences suggest that oxidative stress may play a role in the pathogenesis of the disease, but the significance and precise extent of this contribution is poorly understood. In this paper we show that Becker Muscular Dystrophy (BMD) and Duchenne Muscular Dystrophy (DMD) skin fibroblasts are more susceptible to H2O2 treatment than are fibroblasts from unaffected persons. In particular, we found that, in growing DMD skin fibroblasts, the oxidative treatment resulted in significantly reduced growing capacity. We also investigated the concentrations of intracellular calcium during H2O2 treatment. The intracellular free calcium concentration increased by 22%, 35%, and 40% in unaffected, BMD, and DMD fibroblasts, respectively. However, the increase of the intracellular free calcium concentration is not related, as previously hypothesized, to a reduction of acylphosphatase concentrations, which seem to be unaffected by the H2O2 treatment, but rather to reduced enzyme activity.
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PMID:Oxidative stress and calcium homeostasis in dystrophic skin fibroblasts. 1063 67

Myostatin plays negative roles in muscle development. To block the inhibitory effects of myostatin on myogenesis, a 759 bp single chain variable fragment antibody (scFv) against myostatin was constructed and expressed in Escherichia coli. ELISA detection showed that the scFv could bind to myostatin, and change of the scFv N-terminal peptides decreased its binding affinity. MTT assay and cell morphology demonstrated that the cell number and viability of the C2C12 myoblast were enhanced by the scFv. Meanwhile, the scFv significantly inhibited the myostatin-induced expression of cyclin-dependent kinase inhibitor p21 and Smad binding element-luciferase activity. H2O2 increased the expression of Muscle RING Finger 1 (MuRF1) and Muscle Atrophy F-box (MAFbx) in myoblasts as well as myostatin and MuRF1 in myotubes, and the scFv significantly decreased the H2O2-elevated expression of these genes. Conclusively, the scFv we developed could antagonize the inhibitory effects of myostatin on myogenesis through Smad pathway and regulation of p21, MuRF1 and MAFbx gene expression. The scFv may have application in the therapy of muscular dystrophy and improvement of animal meat production.
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PMID:Construction, expression and characterization of a single chain variable fragment antibody against human myostatin. 2391 79