Muscle-specific overexpression of IGF-I improves E-C coupling in skeletal muscle fibers from dystrophic mdx mice.
Muscle-specific overexpression of IGF-I improves E-C coupling in skeletal muscle fibers from dystrophic mdx mice.
复制标题
IGF-I 的肌肉特异性过度表达可改善营养不良 mdx 小鼠骨骼肌纤维中的 E-C 耦合。
DOI：
10.1152/ajpcell.00399.2007
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发表时间：
2008
期刊：
影响因子：
--
通讯作者：
G. Lynch
中科院分区：
文献类型：
--
作者：
J. Schertzer;C. van der Poel;T. Shavlakadze;M. Grounds;G. Lynch
杜氏肌营养不良症 (DMD) 是一种由功能性肌营养不良蛋白缺失引起的致命性 X 连锁疾病。据报道，mdx 小鼠的营养不良肌纤维存在异常的兴奋-收缩 (E-C) 耦合，并且 E-C 耦合成分的改变可能是肌营养不良蛋白缺乏的直接结果。我们假设肌肉特异性的胰岛素生长因子-1 (IGF-I) 过度表达会减少 mdx 肌肉中的 E-C 耦合失败。机械剥皮的 mdx 小鼠趾长伸肌纤维显示去极化诱导力反应 (DIFR) 下降更快；然而，与非营养不良对照相比，肌浆网（SR）介导的Ca（2+）再吸收或收缩器官的特性没有差异。骨骼肌中过度表达 IGF-I 的转基因 mdx 小鼠（mdx/IGF-I 小鼠）的纤维中 DIFR 下降率恢复至对照水平。营养不良的肌肉具有较低的特定二氢吡啶受体 (DHPR) 同工型转录水平，IGF-I 介导的 E-C 耦合变化与参与 Ca(2+) 调节的特定 DHPR 同工型转录水平增加相关。重要的是，IGF-I 过度表达还增加了收缩装置对 Ca(2+) 的敏感性。结果表明，IGF-I 可以改善营养不良的肌纤维中 E-C 偶联失败的基本方面，并且这些作用对于改善该生长因子诱导的细胞功能非常重要。
Duchenne muscular dystrophy (DMD) is a lethal X-linked disease caused by the absence of functional dystrophin. Abnormal excitation-contraction (E-C) coupling has been reported in dystrophic muscle fibers from mdx mice, and alterations in E-C coupling components may occur as a direct result of dystrophin deficiency. We hypothesized that muscle-specific overexpression of insulin-growth factor-1 (IGF-I) would reduce E-C coupling failure in mdx muscle. Mechanically skinned extensor digitorum longus muscle fibers from mdx mice displayed a faster decline in depolarization-induced force responses (DIFR); however, there were no differences in sarcoplasmic reticulum (SR)-mediated Ca(2+) resequestration or in the properties of the contractile apparatus when compared with nondystrophic controls. The rate of DIFR decline was restored to control levels in fibers from transgenic mdx mice that overexpressed IGF-I in skeletal muscle (mdx/IGF-I mice). Dystrophic muscles have a lower transcript level of a specific dihydropyridine receptor (DHPR) isoform, and IGF-I-mediated changes in E-C coupling were associated with increased transcript levels of specific DHPR isoforms involved in Ca(2+) regulation. Importantly, IGF-I overexpression also increased the sensitivity of the contractile apparatus to Ca(2+). The results demonstrate that IGF-I can ameliorate fundamental aspects of E-C coupling failure in dystrophic muscle fibers and that these effects are important for the improvements in cellular function induced by this growth factor.
IGF-1 的持续过度表达可防止小鼠骨骼肌中电荷运动和细胞内 Ca(2) 随年龄增长而减少。
影响因子：
3.4
作者：
Wang,Zhong-Min;Messi,MaríaLaura;Delbono,Osvaldo
通讯作者：
Delbono,Osvaldo