PMID: 16521476Mar 9, 2006Paper

Characterization of initiator and effector caspase expressions in dystrophinopathies

Neuropathology : Official Journal of the Japanese Society of Neuropathology
Dominique S Tews

Abstract

There is evidence that apoptotic cell death mechanisms contribute to muscle fiber loss in dystrophin-deficient muscle but there is little knowledge about the final degrading events of muscle fiber apoptosis. In muscle biopsy specimens from 14 patients with a dystrophinopathy (10 patients with DMD, two with Becker MD, two DMD carriers), expression of APAF-1 and caspase-9, upstream members of the apoptotic protease cascade, as well as of the downstream executioners caspase-2, -6 and -7, were studied by immunohistochemistry and Western blots. Besides predominant immunoreactivity in regenerating muscle fibers, which may contribute to apoptotic events during new muscle fiber formation, caspase-9, -6 and -7 displayed upregulation in non-regenerating, light microscopically intact but atrophic muscle fibers. Western blot analyses confirmed the upregulations. These findings indicate that, once activated, caspase-9 initiates a proteolytic, muscle fiber degrading cascade involving the downstream executioners caspase-6 and -7. However, lacking coexpression of APAF-1 suggests the existence of other pathways of caspase-9 activation than through the "apoptosome" in dystrophinopathies.

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Citations

Jan 4, 2008·Heart Failure Reviews·Eloisa ArbustiniJagat Narula
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