title: Characterization of initiator and effector caspase expressions in dystrophinopathies.
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.
authors.affiliation: Neurological (Edinger-) Institute, Johann Wolfgang Goethe University Hospital, Frankfurt/M, Germany. dominique-suzanne.tews@kgu.de
authors.forename: Dominique S
authors.initials: DS
authors.lastname: Tews
mesh_terms: D017209:Apoptosis / Q000502:physiology*; D053477:Apoptotic Protease-Activating Factor 1; D015153:Blotting, Western; D020169:Caspases / Q000096:biosynthesis*; D016189:Dystrophin / Q000172:deficiency; D004789:Enzyme Activation / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000201:enzymology / Q000473:pathology; D009136:Muscular Dystrophies / Q000201:enzymology* / Q000473:pathology*; D011506:Proteins / Q000378:metabolism
chemical_list: C506592:APAF1 protein, human; D053477:Apoptotic Protease-Activating Factor 1; D016189:Dystrophin; D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins; D020169:Caspases