Chopard A, Arrighi N, Carnino A, Marini J F
Laboratoire de Physiologie des Systèmes Intégrés, CNRS UMR 6548, Nice, France.
FASEB J. 2005 Oct;19(12):1722-4. doi: 10.1096/fj.04-3336fje. Epub 2005 Jul 26.
This study was designed to evaluate the effects of hypokinesia and hypodynamia on cytoskeletal and related protein contents in human skeletal muscles. Twelve proteins: dystrophin and its associated proteins (DGC), dysferlin, talin, vinculin and meta-vinculin, alpha-actinin, desmin, actin, and myosin, were quantitatively analyzed during an 84-day long-term bedrest (LTBR). The preventive or compensatory effects of maximal resistance exercise (MRE) as a countermeasure were evaluated. Most of these proteins are involved in several myopathies, and they play an important role in muscle structure, fiber cohesion, cell integrity maintenance, and force transmission. This is the first comparison of the cytoskeletal protein contents between slow postural soleus (SOL) and mixed poly-functional vastus lateralis (VL) human muscles. Protein contents were higher in VL than in SOL (from 12 to 94%). These differences could be mainly explained by the differential mechanical constraints imposed on the muscles, i.e., cytoskeletal protein contents increase with mechanical constraints. After LTBR, proteins belonging to the DGC, dysferlin, and proteins of the costamere exhibited large increases, higher in SOL (from 67 to 216%) than in VL (from 32 to 142%). Plasma membrane remodeling during muscle atrophy is probably one of the key points for interpreting these modifications, and mechanisms other than those involved in the resistance of the cytoskeleton to mechanical constraints may be implicated (membrane repair). MRE compensates the cytoskeletal changes induced by LTBR in SOL, except for gamma-sarcoglycan (+70%) and dysferlin (+108%). The exercise only partly compensated the DGC changes induced in VL, and, as for SOL, dysferlin remained largely increased (+132%). Moreover, vinculin and metavinculin, which exhibited no significant change in VL after LTBR, were increased with MRE during LTBR, reinforcing the pre-LTBR differences between SOL and VL. This knowledge will contribute to the development of efficient space flight countermeasures and rehabilitation methods in clinical situations where musculoskeletal unloading is a component.
本研究旨在评估运动减少和动力不足对人体骨骼肌细胞骨架及相关蛋白含量的影响。在为期84天的长期卧床休息（LTBR）期间，对12种蛋白质进行了定量分析，这些蛋白质包括肌营养不良蛋白及其相关蛋白（DGC）、肌膜蛋白、踝蛋白、纽蛋白和变构纽蛋白、α-辅肌动蛋白、结蛋白、肌动蛋白和肌球蛋白。评估了最大阻力运动（MRE）作为一种对策的预防或补偿作用。这些蛋白质大多与几种肌病有关，它们在肌肉结构、纤维黏附、细胞完整性维持和力传递中发挥重要作用。这是首次对慢肌比目鱼肌（SOL）和混合多功能股外侧肌（VL）这两种人体肌肉的细胞骨架蛋白含量进行比较。VL中的蛋白含量高于SOL（从12%到94%）。这些差异主要可以通过施加在肌肉上的不同机械约束来解释，即细胞骨架蛋白含量随机械约束增加。LTBR后，属于DGC、肌膜蛋白和肌节相关蛋白的蛋白质大幅增加，SOL中的增加幅度（从67%到216%）高于VL（从32%到142%）。肌肉萎缩期间的质膜重塑可能是解释这些变化的关键点之一，可能涉及除细胞骨架对机械约束的抗性之外的其他机制（膜修复）。MRE补偿了LTBR在SOL中引起的细胞骨架变化，但γ-肌聚糖（增加70%）和肌膜蛋白（增加108%）除外。运动仅部分补偿了LTBR在VL中引起的DGC变化，并且与SOL一样，肌膜蛋白仍大幅增加（增加132%）。此外，LTBR后在VL中无显著变化的纽蛋白和变构纽蛋白，在LTBR期间随MRE增加，强化了LTBR前SOL和VL之间的差异。这些知识将有助于开发有效的太空飞行对策以及在肌肉骨骼卸载是一个因素的临床情况下的康复方法。
