Altered myofilament function depresses force generation in patients with nebulin-based nemaline myopathy (NEM2).
Altered myofilament function depresses force generation in patients with nebulin-based nemaline myopathy (NEM2).
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DOI：
10.1016/j.jsb.2009.11.013
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发表时间：
2010-05
影响因子：
3
通讯作者：
Granzier, Henk
中科院分区：
文献类型：
--
作者：
Ottenheijm, Coen A. C.;Hooijman, Pleuni;DeChene, Elizabeth T.;Stienen, Ger J.;Beggs, Alan H.;Granzier, Henk
线状体肌病（NM）是最常见的非营养不良性先天性肌病，临床上以肌无力为特征。然而，这种弱点背后的机制知之甚少。在这里，我们研究了收缩表型的骨骼肌从NM患者与nebulin突变（NEM 2）。SDS-PAGE和蛋白质印迹法研究显示，显着减少nebulin蛋白质水平在肌肉从NM患者，而其他薄的免疫基础蛋白质的水平没有显着改变。肌肉力学研究表明，显着降低的力产生在NM肌纤维的钙敏感性相比，控制纤维。此外，我们发现较慢的速率常数的力量重建，以及增加的张力成本，在NM相比，控制纤维，表明在NM肌肉的跨桥连接的速度降低，而跨桥脱离的速度增加。由此产生的力产生横桥的分数减少预计将大大削弱NM患者肌肉的力产生能力。因此，本研究提供了重要的新的见解，肌无力的发病机制，在星云蛋白为基础的NM。
Nemaline myopathy (NM), the most common non-dystrophic congenital myopathy, is clinically characterized by muscle weakness. However, the mechanisms underlying this weakness are poorly understood. Here, we studied the contractile phenotype of skeletal muscle from NM patients with nebulin mutations (NEM2). SDS-PAGE and Western blotting studies revealed markedly reduced nebulin protein levels in muscle from NM patients, whereas levels of other thin filament-based proteins were not significantly altered. Muscle mechanics studies indicated significantly reduced calcium sensitivity of force generation in NM muscle fibers compared to control fibers. In addition, we found slower rate constant of force redevelopment, as well as increased tension cost, in NM compared to control fibers, indicating that in NM muscle the rate of cross bridge attachment is reduced, whereas the rate of cross bridge detachment is increased. The resulting reduced fraction of force generating cross bridges is expected to greatly impair the force generating capacity of muscle from NM patients. Thus, the present study provides important novel insights into the pathogenesis of muscle weakness in nebulin-based NM.
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影响因子：
2.9
作者：
LYMN, RW;TAYLOR, EW
通讯作者：
TAYLOR, EW
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作者：
SHIMOMURA, C;NONAKA, I
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作者：
Ottenheijm, Coen A. C.;Witt, Christian C.;Granzier, Henk
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Granzier, Henk
影响因子：
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作者：
Ryan, MM;Ilkovski, B;Beggs, AH
通讯作者：
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