DYSTROPHIN PROTECTS THE SARCOLEMMA FROM STRESSES DEVELOPED DURING MUSCLE-CONTRACTION
DYSTROPHIN PROTECTS THE SARCOLEMMA FROM STRESSES DEVELOPED DURING MUSCLE-CONTRACTION
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DOI：
10.1073/pnas.90.8.3710
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发表时间：
1993-04-15
影响因子：
11.1
通讯作者：
SWEENEY, HL
中科院分区：
文献类型：
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作者：
PETROF, BJ;SHRAGER, JB;SWEENEY, HL
通常在骨骼肌细胞膜的细胞质表面上发现的蛋白质肌营养不良蛋白在杜氏肌营养不良症患者以及mdx（X连锁肌营养不良症）小鼠中不存在。虽然其一级结构已经确定，肌营养不良蛋白的确切功能仍然是推测的主题。在本研究中，我们证明了mdx小鼠肌营养不良蛋白缺乏的肌纤维表现出对收缩诱导的肌膜破裂的敏感性增加。肌膜损伤的程度与收缩期间施加在膜上的机械应力的大小直接相关，而不是与肌肉的激活次数直接相关。这些发现有力地支持了肌营养不良蛋白的主要功能是为肌膜提供机械强化，从而保护其免受肌肉收缩过程中产生的膜应力的影响。此外，在这项研究中使用的方法应该证明是有用的，在mdx小鼠的抗肌萎缩蛋白基因治疗的疗效评估。
The protein dystrophin, normally found on the cytoplasmic surface of skeletal muscle cell membranes, is absent in patients with Duchenne muscular dystrophy as well as mdx (X-Linked muscular dystrophy) mice. Although its primary structure has been determined, the precise functional role of dystrophin remains the subject of speculation. In the present study, we demonstrate that dystrophin-deficient muscle fibers of the mdx mouse exhibit an increased susceptibility to contraction-induced sarcolemmal rupture. The level of sarcolemmal damage is directly correlated with the magnitude of mechanical stress placed upon the membrane during contraction rather than the number of activations of the muscle. These findings strongly support the proposition that the primary function of dystrophin is to provide mechanical reinforcement to the sarcolemma and thereby protect it from the membrane stresses developed during muscle contraction. Furthermore, the methodology used in this study should prove useful in assessing the efficacy of dystrophin gene therapy in the mdx mouse.