Molecular and cellular contractile dysfunction of dystrophic muscle from young mice.
Molecular and cellular contractile dysfunction of dystrophic muscle from young mice.
复制标题
年轻小鼠营养不良性肌肉的分子和细胞收缩功能障碍。
DOI：
10.1002/mus.20562
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发表时间：
2006
期刊：
影响因子：
3.4
通讯作者：
Grange,RobertW
中科院分区：
文献类型：
--
作者：
Lowe,DawnA;Williams,BrianO;Thomas,DavidD;Grange,RobertW
本研究的目的是确定收缩蛋白的改变是否是导致年轻营养不良性肌肉力量不足的原因。测定了 21 天和 35 天的野生型 (wt)、肌营养不良蛋白缺陷 (mdx) 和肌营养不良蛋白/肌营养不良蛋白 (mdx:utrn−/−) 小鼠的完整趾长伸肌和透化纤维的收缩性。通过定点自旋标记和电子顺磁共振波谱评估肌球蛋白结构动力学。主要发现是，mdx肌肉中的力量产生被抑制约20%，但纤维Ca2+激活的力量和肌球蛋白结构与wt动物没有不同，这表明收缩蛋白并不是造成这些肌肉力量不足的原因。 Formdx：utrn−/−小鼠的肌肉和纤维力量比 wt 低约 40%，收缩过程中强结合肌球蛋白的比例减少了 13%。这些数据表明，除了肌球蛋白功能障碍之外，收缩蛋白的改变也会导致 youngmdx:utrn−/− 小鼠的肌肉力量不足。阐明疾病发作时肌肉无力的分子机制对于设计治疗策略非常重要。肌肉神经，2006
The purpose of this study was to determine whether contractile protein alterations are responsible for force deficits in young dystrophic muscle. Contractility of intact extensor digitorum longus muscles and permeabilized fibers from wild‐type (wt), dystrophin‐deficient (mdx), and dystrophin/utrophin‐deficient (mdx:utrn−/−) mice aged 21 and 35 days was determined. Myosin structural dynamics were assessed by site‐directed spin labeling and electron paramagnetic resonance spectroscopy. The principal finding was that force generation was depressed by ∼20% inmdxmuscles, but fiber Ca2+‐activated force and myosin structure were not different from wt animals, suggesting that contractile proteins are not responsible for the force deficits in those muscles. Formdx:utrn−/−mice, muscle and fiber forces were ∼40% lower than wt and the fraction of strong‐binding myosin during contraction was reduced by 13%. These data indicate that contractile protein alterations, in addition to myosin dysfunction, cause force deficit in muscles from youngmdx:utrn−/−mice. Elucidating the molecular mechanisms underlying muscle weakness at the onset of disease is important for designing treatment strategies. Muscle Nerve, 2006