title: Loss of dystrophin and some dystrophin-associated proteins with concomitant signs of apoptosis in rat leg muscle overworked in extension.
abstract: This study investigated the basis for the high severity of damage to skeletal muscle due to eccentric exercise, i.e., to muscles generating force while lengthened. Fast and slow rat leg muscles maintained in an extended position were examined after 2-24 h of continuous stimulation. The treatment caused the injury to some regions of both muscles. Within the better preserved parts of the muscles, i.e., those without signs of necrotic processes, dystrophin, spectrin, and some of the dystrophin-associated proteins (beta-dystroglycan, alpha-sarcoglycan, and gamma-sarcoglycan) disappeared from sarcolemma of many fibers. The reduction or loss of dystrophin from the sarcolemma was more evident than that of other proteins examined, with sarcoglycans apparently being the most preserved. Several muscle fibers devoid of dystrophin contained apoptotic nuclei. Simultaneously, Bax, Bcl-2 and caspase-3 proteins appeared in many fibers. Our results indicate that a normal muscle overworking in an extended position undergoes the loss of several membrane skeletal proteins because of the excessive stress to the membrane cytoskeleton, which can lead to fiber death by either apoptosis or necrosis. This experimental model may represent a good model for mimicking the pathogenetic events in several muscular dystrophies.
authors.affiliation: C.N.R. Unit for Muscle Biology and Physiopathology, Padova, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Biral
authors.forename: A
authors.initials: A
authors.lastname: Jakubiec-Puka
authors.forename: I
authors.initials: I
authors.lastname: Ciechomska
authors.forename: M
authors.initials: M
authors.lastname: Sandri
authors.forename: K
authors.initials: K
authors.lastname: Rossini
authors.forename: U
authors.initials: U
authors.lastname: Carraro
authors.forename: R
authors.initials: R
authors.lastname: Betto
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism; D049030:Dystroglycans; D016189:Dystrophin / Q000378:metabolism*; D004558:Electric Stimulation; D005260:Female; D020287:In Situ Nick-End Labeling / Q000706:statistics & numerical data; D008562:Membrane Glycoproteins / Q000378:metabolism; D009119:Muscle Contraction / Q000502:physiology; D018763:Muscle Fatigue / Q000502:physiology*; D018656:Muscle Fibers, Fast-Twitch / Q000378:metabolism / Q000473:pathology; D018485:Muscle Fibers, Skeletal / Q000378:metabolism* / Q000473:pathology*; D018657:Muscle Fibers, Slow-Twitch / Q000378:metabolism / Q000473:pathology; D018482:Muscle, Skeletal / Q000293:injuries / Q000378:metabolism* / Q000473:pathology; D010805:Physical Conditioning, Animal / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D049031:Sarcoglycans; D051028:bcl-2-Associated X Protein
chemical_list: C494828:Bax protein, rat; D003598:Cytoskeletal Proteins; D016189:Dystrophin; D008562:Membrane Glycoproteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D049031:Sarcoglycans; D051028:bcl-2-Associated X Protein; D049030:Dystroglycans; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases