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Evidence of oxidative stress in mdx mouse muscle: studies of the pre-necrotic state
- Source :
- Journal of the neurological sciences. 161(1)
- Publication Year :
- 1999
-
Abstract
- Considerable evidence indicates that free radical injury may underlie the pathologic changes in muscular dystrophies from mammalian and avian species. We have investigated the role of oxidative injury in muscle necrosis in mice with a muscular dystrophy due to a defect in the dystrophin gene (the mdx strain). In order to avoid secondary consequences of muscle necrosis, all experiments were done on muscle prior to the onset of the degenerative process (i.e. during the `pre-necrotic' phase) which lasted up to 20 days of age in the muscles examined. In pre-necrotic mdx muscle, there was an induction of expression of genes encoding antioxidant enzymes, indicative of a cellular response to oxidative stress. In addition, the levels of lipid peroxidation were greater in mdx muscle than in the control. Since the free radical nitric oxide (NO ⋅ ) has been shown to mediate oxidative injury in various disease states, and because dystrophin has been shown to form a complex with the enzyme nitric oxide synthase, we examined pre-necrotic mdx muscle for evidence of NO ⋅ -mediated injury by measuring cellular nitrotyrosine formation. By both immunohistochemical and electrochemical analyses, no evidence of increased nitrotyrosine levels in mdx muscle was detected. Therefore, although no relationship with NO ⋅ -mediated toxicity was found, we found evidence of increased oxidative stress preceding the onset of muscle cell death in dystrophin-deficient mice. These results lend support to the hypothesis that free radical-mediated injury may contribute to the pathogenesis of muscular dystrophies.
- Subjects :
- musculoskeletal diseases
medicine.medical_specialty
mdx mouse
Gene Expression
medicine.disease_cause
Nitric Oxide
Nitric oxide
chemistry.chemical_compound
Mice
Necrosis
Reference Values
Internal medicine
medicine
Myocyte
Animals
Muscular dystrophy
biology
Nitrotyrosine
Muscles
medicine.disease
Nitric oxide synthase
Mice, Inbred C57BL
Oxidative Stress
Endocrinology
Neurology
chemistry
Biochemistry
biology.protein
Mice, Inbred mdx
Tyrosine
Neurology (clinical)
Dystrophin
Oxidoreductases
Oxidative stress
Subjects
Details
- ISSN :
- 0022510X
- Volume :
- 161
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Journal of the neurological sciences
- Accession number :
- edsair.doi.dedup.....cce26127a8ad9269073151ab459e28a0