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)

To estimate the oxidative damage to skeletal muscle DNA in mitochondrial encephalomyopathies, we studied the amount of 8-hydroxy-deoxyguanosine (8-OH-dG) and the localization of superoxide dismutase (SOD) in the skeletal muscles of patients with progressive external ophthalmoplegia (PEO) or Kearns-Sayre syndrome (KSS). The molar ratio of 8-OH-dG/deoxyguanosine in skeletal muscle from PEO or KSS patients was significantly higher than the control value. The ratio from patients with polymyositis or Duchenne's muscular dystrophy was not significantly elevated. Immunohistochemical staining for both Mn-SOD and Cu,Zn-SOD showed pronounced staining in the subsarcolemmal and intermyofibrillar regions of cytochrome-oxidase-negative ragged red fibers of KSS or PEO muscles. Our findings suggest that overproduction of 8-OH-dG and mitochondrial dysfunction with gene deletions are associated with each other in muscle cells of patients with PEO or KSS, and that free radicals may play an important role in the pathophysiology of mitochondrial encephalomyopathies.
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PMID:Oxidative damage to skeletal muscle DNA from patients with mitochondrial encephalomyopathies. 883 81

Nitric oxide (*NO) and its by-products modulate many physiological functions of skeletal muscle including blood flow, metabolism, glucose uptake, and contractile function. However, growing evidence suggests that an overproduction of nitric oxide contributes to muscle wasting in a number of pathologies including chronic heart failure, sepsis, COPD, muscular dystrophy, and extreme disuse. Limited data point to the potential of inhibition various enzymes by reactive nitrogen species (RNS), including (.)NO and its downstream products such as peroxynitrite, primarily in purified systems. We hypothesized that exposure of skeletal muscle to RNS donors would reduce or downregulate activities of the crucial antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX). Diaphragm muscle fiber bundles were extracted from 4-month-old Fischer-344 rats and, in a series of experiments, exposed to either (a) 0 (control), 1, or 5 mM diethylamine NONOate (DEANO: *NO donor); (b) 0, 100, 500 microM, or 1 mM sodium nitroprusside (SNP: *NO donor); (c) 0 or 2 mM S-nitroso-acetylpenicillamine (SNAP: *NO donor); or (d) 0 or 500 microM SIN-1 (peroxynitrite donor) for 60 min. DEANO resulted in a 50% reduction in CAT, GPX, and a dose-dependent inhibition of Cu, Zn-SOD. SNP resulted in significantly lower activities for total SOD, Mn-SOD isoform, Cu, Zn-SOD isoform, CAT, and GPX in a dose-dependent fashion. Two millimolar SNAP and 500 microM SIN-1 also resulted in a large and significant inhibition of total SOD and CAT. These data indicate that reactive nitrogen species impair antioxidant enzyme function in an RNS donor-specific and dose-dependent manner and are consistent with the hypothesis that excess RNS production contributes to skeletal muscle oxidative stress and muscle dysfunction.
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PMID:Specificity of antioxidant enzyme inhibition in skeletal muscle to reactive nitrogen species donors. 1207 89

Astrocytes in the cerebrum and medulla oblongata of cases of Fukuyama type congenital muscular dystrophy were examined by immunohistochemistry of oxidative modification products and free-radical scavenging enzymes because abnormal glia limitans formed by astrocytic end feet is considered to be involved in the genesis of brain lesions of Fukuywama type congenital muscular dystrophy. The study was performed on two fetal cases of Fukuyama type congenital muscular dystrophy of 18 and 20 weeks' gestation and seven patients with Fukuyama type congenital muscular dystrophy ranging in age from 2 to 27 years. Eight age-matched control cases were used. Polymerase chain reaction (PCR) was performed to ascertain the gene phenotype of two child cases, in which prenatal gene analysis was not performed. Astrocytes, especially layer I astrocytes, of postnatal cases of Fukuyama type congenital muscular dystrophy were weakly positivefor Nepsilon-(carboxymethyl)lysine and argpyrimidine, suggesting that they were sensitive to oxidative stress, and the accumulation may be related to the abnormal glia limitans. Secondary increase of manganese (Mn) superoxide dismutase against the increase of free radicals was considered in patients with Fukuyama type congenital muscular dystrophy more than 14 years old considered to be homozygous for founder haplotype: homozygosity was suggested by PCR in two cases. In contrast, expression of Mn superoxide dismutase was decreased in 2- and 6-year-old children with Fukuyama type congenital muscular dystrophy that were heterozygous. Moreover, accumulation of argpyrimidine was exclusively found in astrocytes of the 2-year-old child that exhibited severe brain lesions. Function of astrocytes might be impaired or immature in severe or heterozygous cases. These results may confirm that astrocytes play an important role in the etiology of the brain lesion.
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PMID:Oxidative stress in the brain of Fukuyama type congenital muscular dystrophy: immunohistochemical study on astrocytes. 1258 16