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Query: UMLS:C0026850 (muscular dystrophy)
 5,870 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Oxidative injury underlies the cellular injury and cell death in a variety of disease states. In muscular dystrophies, evidence from in vivo and in vitro studies suggests that muscle degeneration may be secondary to an increased susceptibility to oxidative stress. To address the role of free radical metabolism in the pathogenetic process of muscular dystrophies, we examined the muscle of transgenic mice that overexpress copper/zinc (Cu/Zn) superoxide dismutase. Overexpression of this enzyme can sensitize cells to oxidative injury, and Cu/Zn superoxide dismutase activity was elevated approximately fourfold above control levels in skeletal muscle of the transgenic strain. Examination of serum creatine phosphokinase levels in these mice revealed significant elevations after 2 months of age, indicative of active muscle breakdown. By 8 months of age, there was gross atrophy of the quadriceps muscle, and other hindlimb muscles were variably affected. Histologically, there was evidence of widespread muscle necrosis and regeneration, fiber splitting, and replacement of muscle with adipose and fibrous connective tissue, typical of a muscular dystrophy. Associated with the development of this degeneration was an increase in the levels of lipid peroxidation in the muscle of Cu/Zn superoxide dismutase transgenic mice, highlighting the central role of oxidative injury in this pathogenetic process. These results demonstrate that oxidative damage can be the primary pathogenetic process underlying a muscular dystrophy.
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PMID:Overexpression of copper/zinc superoxide dismutase: a novel cause of murine muscular dystrophy. 1040 94

BACKGROUND Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder characterized by progressive muscular dystrophy and paralysis; most ALS patients die from respiratory failure within 3 to 5 years, and there is currently no effective treatment. Some studies have indicated sex differences in the incidence of ALS, and evidence suggests a neuroprotective role for estrogen. MATERIAL AND METHODS We used human Cu/Zn superoxide dismutase (hSOD1-G93A) transgenic mice to determine the effects of ovariotomy on the onset of disease and behavior; we also used Western blotting to measure the expression of aromatase and estrogen receptors, as well as the inflammatory cytokines and apoptosis markers, in the lumbar spinal cord to determine the mechanism of estrogen-mediated neuroprotection. RESULTS Ovariectomy advanced the onset of disease, down-regulated aromatase and estrogen receptor alpha (ER-a) expression, and inhibited expression of the anti-inflammatory factors arginase-1 and the anti-apoptotic factor B-cell lymphoma-2 (Bcl-2) in the lumbar spinal cord of hSOD1-G93A transgenic mice. CONCLUSIONS Ovariectomy resulted in earlier disease onset and attenuated the anti-inflammatory and anti-apoptotic actions of estrogen in hSOD1-G93A transgenic mice. Therefore, estrogen may play an important role in protecting spinal cord motor neurons.
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PMID:Effects of Ovariectomy in an hSOD1-G93A Transgenic Mouse Model of Amyotrophic Lateral Sclerosis (ALS). 2939 43