title: Glutathione depletion during experimental damage to rat skeletal muscle and its relevance to Duchenne muscular dystrophy.
abstract: 1. The release of glutathione has been studied in comparison with the release of creatine kinase from isolated rat soleus muscles subjected to certain forms of experimental damage. 2. Excessive electrically stimulated contractile activity or treatment of muscles with the mitochondrial inhibitor, 2,4-dinitrophenol, induced a substantial release of both creatine kinase and glutathione and a reduction in the total glutathione content of the muscle. The time course of this release and depletion indicates that the efflux of the two molecules is not directly related and that a reduction in muscle glutathione content does not occur before cytosolic enzyme release. 3. 2,4-Dinitrophenol-stimulated release of creatine kinase was significantly reduced by the omission of external calcium from the incubation media, but glutathione release and depletion was relatively unaffected by this. Deliberate elevation of the muscle intracellular calcium content with the calcium ionophore, A23187, induced a substantial loss of creatine kinase, but had no significant effect on the release of glutathione. 4. Muscle biopsies from patients with Duchenne muscular dystrophy were found to have an elevated content of glutathione and an equivalent protein-thiol content compared with control subjects. 5. We conclude that, although release of glutathione from skeletal muscle occurs after excessive contractile activity or inhibition of mitochondrial metabolism, this is not a key step in the damaging processes leading to cytosolic enzyme release, neither is it relevant to the ongoing damage to skeletal muscle which occurs in patients with Duchenne muscular dystrophy.
authors.affiliation: Department of Medicine, University of Liverpool, U.K.
authors.forename: M J
authors.initials: MJ
authors.lastname: Jackson
authors.forename: M H
authors.initials: MH
authors.lastname: Brooke
authors.forename: K
authors.initials: K
authors.lastname: Kaiser
authors.forename: R H
authors.initials: RH
authors.lastname: Edwards
mesh_terms: D019297:2,4-Dinitrophenol; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D003402:Creatine Kinase / Q000378:metabolism; D004140:Dinitrophenols / Q000494:pharmacology; D004195:Disease Models, Animal; D004558:Electric Stimulation; D005260:Female; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D009119:Muscle Contraction / Q000502:physiology; D009132:Muscles / Q000293:injuries / Q000378:metabolism*; D009136:Muscular Dystrophies / Q000378:metabolism*; D009137:Muscular Dystrophy, Animal / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D014475:Uncoupling Agents / Q000494:pharmacology
chemical_list: D004140:Dinitrophenols; D014475:Uncoupling Agents; D000001:Calcimycin; D003402:Creatine Kinase; D005978:Glutathione; D019297:2,4-Dinitrophenol; D002118:Calcium