RT Journal Article
SR Electronic
T1 Greater Susceptibility of the Sarcoplasmic Reticulum to H<sub>2</sub>O<sub>2</sub> Injuries in Diaphragm Muscle from <em>mdx</em> Mice
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 1359
OP 1367
DO 10.1124/jpet.106.103291
VO 318
IS 3
A1 Aude Lafoux
A1 Alexandra Divet
A1 Pascal Gervier
A1 Corinne Huchet-Cadiou
YR 2006
UL http://jpet.aspetjournals.org/content/318/3/1359.abstract
AB The aim of the present study was to investigate the direct effects of a reactive oxygen species, H2O2, 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 1mMH2O2 had similar effects on the maximal Ca2+-activated tension and on the Ca2+ sensitivity of the contractile apparatus of diaphragm fibers in Bl10 and mdx mice. The effects of H2O2 were also assessed on sarcoplasmic reticulum function using saponin-skinned fibers and sarcoplasmic reticulum vesicle preparations. We found that H2O2 induced changes in sarcoplasmic reticulum properties, particularly in the Ca2+ 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 Ca2+ pump in particular, in dystrophin-deficient muscles display increased susceptibility to H2O2 injuries. This suggests that free radicals might, therefore, be involved in the pathophysiological pathway and dysregulation of Ca2+ homeostasis of muscular dystrophy. The American Society for Pharmacology and Experimental Therapeutics