Greater susceptibility of the sarcoplasmic reticulum to H2O2 injuries in diaphragm muscle from mdx mice.
The aim of the present study was to investigate the direct effects of a reactive oxygen species, H(2)O(2), on the contractile function and sarcoplasmic reticulum properties of dystrophin-deficient diaphragm using chemically skinned fibers and sarcoplasmic reticulum vesicle preparations. The results obtained using Triton X-100-skinned fibers demonstrate that exposure to 1 mM H(2)O(2) had similar effects on the maximal Ca(2+)-activated tension and on the Ca(2+) sensitivity of the contractile apparatus of diaphragm fibers in Bl10 and mdx mice. The effects of H(2)O(2) were also assessed on sarcoplasmic reticulum function using saponin-skinned fibers and sarcoplasmic reticulum vesicle preparations. We found that H(2)O(2) induced changes in sarcoplasmic reticulum properties, particularly in the Ca(2+) pump function. The most important finding was that diaphragm muscle from mdx mice displayed increased sensitivity to the oxidant. Furthermore, in isolated superfused diaphragm muscle from mdx mice, the data demonstrate that the amount of superoxide anion produced under fatiguing conditions was increased. Our study shows that the sarcoplasmic reticulum, and the Ca(2+) pump in particular, in dystrophin-deficient muscles display increased susceptibility to H(2)O(2) injuries. This suggests that free radicals might, therefore, be involved in the pathophysiological pathway and dysregulation of Ca(2+) homeostasis of muscular dystrophy.
Lafoux
Aude
A
Université de Nantes, Centre National de la Recherche Scientifique, Unité Mixte Recherche 6204, Biotechnologie, Biocatalyse et Biorégulation, Faculté des Sciences et des Techniques, F-44322 Nantes, Cedex 03, France.
Divet
Alexandra
A
Gervier
Pascal
P
Huchet-Cadiou
Corinne
C
D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D003285:Contractile Proteins / Q000032:analysis; D003964:Diaphragm; D006861:Hydrogen Peroxide / Q000633:toxicity*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D009119:Muscle Contraction / Q000187:drug effects*; D009136:Muscular Dystrophies / Q000378:metabolism*; D017830:Octoxynol / Q000494:pharmacology; D012503:Saponins / Q000494:pharmacology; D012519:Sarcoplasmic Reticulum / Q000187:drug effects* / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism
D003285:Contractile Proteins; D012503:Saponins; D013481:Superoxides; D002110:Caffeine; D017830:Octoxynol; D006861:Hydrogen Peroxide; D000252:Calcium-Transporting ATPases; D002118:Calcium