title: Characterization of ARC, apoptosis repressor interacting with CARD, in normal and dystrophin-deficient skeletal muscle.
abstract: Duchenne muscular dystrophy is an X-linked recessive disorder, primarily characterized by progressive muscle weakness and wasting. The disease results from the absence of dystrophin, however the precise molecular mechanisms leading to muscle pathology are poorly understood. Dystrophic muscles undergo increased oxidative stress and altered calcium homeostasis, which may contribute to myofiber loss by triggering both necrosis and apoptosis. Recent studies have identified ARC (apoptosis repressor with caspase recruitment domain) as an abundant protein in human muscle that can inhibit both hypoxia and caspase-8-induced apoptosis as well as protect cells from oxidative stress. To explore a potential role for ARC in protecting muscle fibers from dystrophic breakdown, we have cloned and characterized murine ARC and studied its expression in normal and dystrophic mouse muscle. ARC is expressed at high levels in striated muscle and displays fiber-type restricted expression patterns. ARC expression levels are normal in dystrophic mdx mice, although the intracellular localization pattern of ARC is slightly altered compared with normal muscles. Overexpression of ARC in transgenic mdx mice failed to alleviate the dystrophic pathology in skeletal muscles, suggesting that misregulation of the molecular pathways regulated by ARC does not significantly contribute to myofiber death.
authors.affiliation: Department of Neurology, University of Washington School of Medicine, Seattle, WA 98195-7720, USA.
authors.forename: S
authors.initials: S
authors.lastname: Abmayr
authors.forename: R W
authors.initials: RW
authors.lastname: Crawford
authors.forename: J S
authors.initials: JS
authors.lastname: Chamberlain
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002463:Cell Membrane Permeability; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D016189:Dystrophin / Q000172:deficiency*; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D051379:Mice; D018101:Mice, Inbred mdx; D008822:Mice, Transgenic; D008928:Mitochondria / Q000378:metabolism; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology; D020388:Muscular Dystrophy, Duchenne / Q000235:genetics / Q000473:pathology; D009928:Organ Specificity; D012016:Reference Values
chemical_list: D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins; D016189:Dystrophin; C436144:LLID-114769 protein, human; D009124:Muscle Proteins; C112246:NOL3 protein, human; C491787:Nol3 protein, mouse; C505407:CASP3 protein, human; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases