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首页> 外文期刊>Canadian Journal of Physiology and Pharmacology >Diaphragm tension reduced in dystrophic mice by an oxidant, hypochlorous acid.
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Diaphragm tension reduced in dystrophic mice by an oxidant, hypochlorous acid.

机译:在营养不良的小鼠中,隔膜张力被氧化剂次氯酸降低。

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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+.
机译:在肌营养不良蛋白缺乏的骨骼肌细胞中,Ca2 +稳态被破坏,活性氧产生增加,我们假设次氯酸(HOCl)是与H2O2相关的强自由基,会破坏收缩蛋白和肌浆网。本研究的目的是研究暴露于应用HOCl(100 micromol / L和1 mmol / L)产生的氧化应激对营养不良小鼠的收缩功能和肌浆网性质的影响。对在mdx小鼠中受到严重影响的diaphragm肌进行了实验,并将结果与​​在健康(非营养不良)小鼠中获得的结果进行了比较。在来自C57BL / 10和mdx小鼠的Triton皮肤纤维中,1 mmol / L HOCl增加了肌原纤维Ca2 +敏感性,但降低了最大的Ca2 +激活张力。在存在HOCl的情况下,需要更高浓度的MgATP以产生严格的张力。 HOCl和Ca2 +吸收机制之间的相互作用是用皂角皮纤维和肌浆网囊泡证明的。结果表明,以微摩尔或毫摩尔浓度的HOCl可以改变肌浆网Ca2 +的吸收,这种作用在mdx小鼠的diaphragm肌中更为明显。我们得出结论,在营养不良的横diaphragm膜骨骼肌细胞中,HOC1激活细胞途径,导致细胞内Ca2 +浓度增加。

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