title: DNA-fragmentation and apoptosis-related proteins of muscle cells in motor neuron disorders.
abstract: Apoptosis has been described as one of the mechanisms of muscle fiber loss in infantile spinal muscular atrophy. In order to investigate if muscle fiber-apoptosis plays a role in other denervating disorders as well, we studied DNA-fragmentation, a hallmark of apoptosis, by the TUNEL-method and, moreover, the expression patterns of apoptosis-related proteins in 2 patients suffering from ALS and in 6 patients with polyneuropathy. We identified DNA-cleavage in muscle fibers of all these patients. Furthermore, we found strong expression of bax and ICE promoting apoptosis in muscle fibers. However, also strong expression of the anti-apoptotic factor bcl-2 was found. Our findings indicate that defective innervation may prompt muscle fibers to activate an intrinsic "suicide" programme which is promoted by the proapoptotic factors bax and ICE, which seems to induce formation of apoptotic bodies by cleavage of actin. Nevertheless, there are also anti-apoptotic strategies in muscle fibers manifested by expression of the bax-antagonist bcl-2 which is able to neutralize high bax levels.
authors.affiliation: Division of Neuropathology, Johannes-Gutenberg-University Medical Center, Mainz, Germany.
authors.forename: D S
authors.initials: DS
authors.lastname: Tews
authors.forename: H H
authors.initials: HH
authors.lastname: Goebel
authors.forename: H M
authors.initials: HM
authors.lastname: Meinck
mesh_terms: D000328:Adult; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism / Q000473:pathology*; D017209:Apoptosis / Q000187:drug effects*; D001284:Atrophy / Q000473:pathology; D018797:Cell Cycle Proteins / Q000378:metabolism*; D003546:Cysteine Endopeptidases / Q000378:metabolism; D053938:DNA Fragmentation; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016472:Motor Neuron Disease / Q000378:metabolism / Q000473:pathology*; D018485:Muscle Fibers, Skeletal / Q000473:pathology*; D018482:Muscle, Skeletal / Q000473:pathology*; D009410:Nerve Degeneration / Q000473:pathology; D010523:Peripheral Nervous System Diseases / Q000378:metabolism / Q000473:pathology*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D016028:Receptors, Leukocyte-Adhesion / Q000378:metabolism; D019014:fas Receptor / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; D011518:Proto-Oncogene Proteins; D016028:Receptors, Leukocyte-Adhesion; D019014:fas Receptor; D003546:Cysteine Endopeptidases