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

Apoptosis plays a major role in several diseases, including viral infections, autoimmune diseases, cancer, cardiac infarct, and neurological disorders. To investigate the role of apoptosis in muscular dystrophy, dystrophin-deficient (mdx) mice were subjected to spontaneous exercise and skeletal muscles were analyzed for apoptosis and ubiquitin. The increase of apoptotic myonuclei after exercise was detected by TUNEL, by electron microscopy, and by DNA analyses for high molecular weight and for ladder fragments. Expression of ubiquitin correlated with exercise and with positive myonuclei for apoptosis. Biochemical analysis confirmed a high level of ubiquitination both in sarcoplasmic and myofibrillar proteins. Muscles from sedentary congenit control mice (C57B ) were negative for apoptosis, while after exercise some nuclei were positive. We also revealed that normal myoblasts committed to apoptosis in vitro showed an increased expression of ubiquitin. Western blot for bcl-2, FasL, and BAG1 showed a significant decrease of bcl-2 product only in mdx mice after exercise. Thus, spontaneous exercise results in the increase of ubiquitin expression and in the reduction of bcl-2 tightly related to programmed cell death in mdx mice. These findings confirm that DNA fragmentation, absent in muscles of sedentary normal mice but present in mdx mice at rest, dramatically increases after exercise, shedding new light on exercise-induced muscle damage and on its progression in dystrophinopathies.
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PMID:Exercise induces myonuclear ubiquitination and apoptosis in dystrophin-deficient muscle of mice. 899 Jan 28

The current view that apoptosis precedes necrosis in death of dystrophin-deficient muscle fibers of the mdx mouse has been well substantiated. Moreover, apoptotic myonuclei have been reported to increase in dystrophin-deficient mice 2 days after spontaneous exercise. To investigate the role of apoptosis in human muscular dystrophy, muscles from 11 patients of different ages with Duchenne muscular dystrophy were analyzed for apoptosis. The amount of apoptosis was assessed by terminal deoxynucleotidyl transferase assay, and the expression of bcl-2 and bax was examined by immunohistochemistry. Although very rare in normal muscles (less than 0.1%), apoptotic nuclei were detected in dystrophic muscles, particularly at the interstitial level. Nevertheless, few dystrophin-deficient myofibers with centrally located nuclei showed a positive reaction for DNA fragmentation. A mosaic pattern of bcl-2/bax-positive myofibers characterized dystrophic muscles, thus the relative proportion of pro- and antiapoptotic proteins differs among muscle fibers in correlation with the presence of apoptotic myonuclei. In the interstitium, apoptotic cells were identified as macrophages and activated satellite cells. This is the first study to show an apoptotic process in adult muscle fibers of patients with Duchenne muscular dystrophy, thereby shedding new light on muscle damage and its progression in dystrophinopathies.
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PMID:Apoptotic myonuclei in human Duchenne muscular dystrophy. 971 87