Diaphragm tension reduced in dystrophic mice by an oxidant, hypochlorous acid.
In dystrophin-deficient skeletal muscle cells, in which Ca2+ homeostasis is disrupted and reactive oxygen species production is increased, we hypothesized that hypochlorous acid (HOCl), a strong H2O2-related free radical, damages contractile proteins and the sarcoplasmic reticulum. The aim of the present study was to investigate the effects of exposure to oxidative stress, generated by applying HOCl (100 micromol/L and 1 mmol/L), on the contractile function and sarcoplasmic reticulum properties of dystrophic mice. Experiments were performed on diaphragm muscle, which is severely affected in the mdx mouse, and the results were compared with those obtained in healthy (non-dystrophic) mice. In Triton-skinned fibres from C57BL/10 and mdx mice, 1 mmol/L HOCl increased myofibrillar Ca2+ sensitivity, but decreased maximal Ca2+-activated tension. In the presence of HOCl, higher concentrations of MgATP were required to produce rigor tensions. The interaction between HOCl and the Ca2+ uptake mechanisms was demonstrated using saponin-skinned fibres and sarcoplasmic reticulum vesicles. The results showed that HOCl, at micromolar or millimolar concentrations, can modify sarcoplasmic reticulum Ca2+ uptake and that this effect was more pronounced in diaphragm muscle from mdx mice. We conclude that in dystrophic diaphragm skeletal muscle cells, HOCl activates a cellular pathway that leads to an increase in the intracellular concentration of Ca2+.
Université de Nantes, CNRS, UMR 6204, Biotechnologie, Biocatalyse et Biorégulation, Faculté des Sciences et des Techniques, 2 rue de la Houssinière, BP 92208, F-44322 Nantes, CEDEX 03, France.
Aude
A
Lafoux
Alexandra
A
Divet
Pascal
P
Gervier
Corinne
C
Huchet-Cadiou
D000818:Animals; D002118:Calcium / Q000378:metabolism; D003964:Diaphragm / Q000187:drug effects* / Q000502:physiology / Q000503:physiopathology; D006997:Hypochlorous Acid / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D009119:Muscle Contraction / Q000187:drug effects* / Q000502:physiology; D009137:Muscular Dystrophy, Animal / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology*; D016877:Oxidants / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000235:genetics / Q000378:metabolism
D016877:Oxidants; D006997:Hypochlorous Acid; D002118:Calcium