Functional classification of skeletal muscle networks. II. Applications to pathophysiology.
Functional classification of skeletal muscle networks. II. Applications to pathophysiology.
复制标题
骨骼肌网络的功能分类。
DOI：
10.1152/japplphysiol.01515.2011
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
Subramaniam,Shankar
中科院分区：
文献类型：
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作者：
Wang,Yu;Winters,Jack;Subramaniam,Shankar
在我们之前的同伴论文中（Wang Y，Winters J，Subramaniam S.J Appl Physiol. doi：10.1152/japplphysiol.01514.2011），我们使用了正常人受试者的广泛表达谱数据，结合传统知识将骨骼肌功能分为四种模型，即兴奋-激活，机械，代谢和信号产生模型家族。在本文中，我们演示了如何将这种分类可以应用于研究两个特点很好的肌病：肌萎缩侧索硬化症（ALS）和杜氏肌营养不良症（DMD）。使用ALS和DMD患者的骨骼肌轮廓数据与正常受试者相比，正常年轻的DMD的情况下，我们描绘的分子机制，是导致和后果骨骼肌功能障碍。在ALS中，我们的分析确定了代谢作用，并特别确定了钙调节异常和线粒体物质转运缺陷的机制，这对肌肉功能障碍很重要。在DMD中，我们说明了受损的机械功能是如何与其他三个功能网络强烈协调的，从而导致骨骼肌转化为混合形式作为一种补偿机制。我们的功能模型还提供了，在精致的细节，在这四个家庭中的无数蛋白质在正常和疾病功能的机制作用。
In our preceding companion paper (Wang Y, Winters J, Subramaniam S.J Appl Physiol. doi: 10.1152/japplphysiol.01514.2011), we used extensive expression profile data on normal human subjects, in combination with legacy knowledge to classify skeletal muscle function into four models, namely excitation-activation, mechanical, metabolic, and signaling-production model families. In this paper, we demonstrate how this classification can be applied to study two well-characterized myopathies: amyotrophic lateral sclerosis (ALS) and Duchenne muscular dystrophy (DMD). Using skeletal muscle profile data from ALS and DMD patients compared with that from normal subjects, normal young in the case of DMD, we delineate molecular mechanisms that are causative and consequential to skeletal muscle dysfunction. In ALS, our analysis establishes the metabolic role and specifically identifies the mechanisms of calcium dysregulation and defects in mitochondrial transport of materials as important for muscle dysfunction. In DMD, we illustrate how impaired mechanical function is strongly coordinated with other three functional networks, resulting in transformation of the skeletal muscle into hybrid forms as a compensatory mechanism. Our functional models also provide, in exquisite detail, the mechanistic role of myriad proteins in these four families in normal and disease function.