title: Effects of iron deprivation on the pathology and stress protein expression in murine X-linked muscular dystrophy.
abstract: Duchenne muscular dystrophy (DMD) is caused by dystrophin deficiency, which results in muscle necrosis and the upregulation of heat shock/stress proteins (HSP). We hypothesized that reactive oxygen species, and in particular hydroxyl radicals (.OH), participate in muscle necrosis and HSP expression. It was assumed that iron deprivation decreases .OH generation, restraining the disease process and reducing the oxidant-induced expression of HSP. The role of iron-catalyzed free radical reactions in the pathology of dystrophin-deficient muscle was evaluated in the murine model for Duchenne muscular dystrophy (mdx), by examining the effects of dietary deficiency and supplementation of iron on serum creatine kinase (CK), muscle morphology, lipid peroxidation and HSP levels in mice maintained on diets deficient in or supplemented with iron for 6 weeks. Iron-deprived mdx mice showed a significant decrease in the number of macrophage-invaded necrotic fibers and the expression of the 70-kDa heat shock protein (Hsp70). This suggests that the iron-dependent generation of .OH relates to muscle necrosis in the mdx mouse and modulates the expression of Hsp70 in vivo. In contrast, iron deprivation had no influence on other HSP or on lipid peroxidation in mdx mice, while maintenance on either diet caused a significant decrease in serum creatine kinase activity. The potential therapeutic effects of iron deprivation in mdx should be considered.
authors.affiliation: Department of Chemistry and Biochemistry, Rand Afrikaans University, Johannesburg, South Africa.
authors.forename: L
authors.initials: L
authors.lastname: Bornman
authors.forename: H
authors.initials: H
authors.lastname: Rossouw
authors.forename: G S
authors.initials: GS
authors.lastname: Gericke
authors.forename: B S
authors.initials: BS
authors.lastname: Polla
mesh_terms: D000818:Animals; D003402:Creatine Kinase / Q000097:blood; D019587:Dietary Supplements; D004195:Disease Models, Animal; D008040:Genetic Linkage; D006360:Heat-Shock Proteins / Q000096:biosynthesis*; D007501:Iron / Q000097:blood; D000090463:Iron Deficiencies; D019266:Iron, Dietary / Q000008:administration & dosage; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000473:pathology; D009137:Muscular Dystrophy, Animal / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D009336:Necrosis; D014960:X Chromosome
chemical_list: D006360:Heat-Shock Proteins; D019266:Iron, Dietary; D007501:Iron; D003402:Creatine Kinase