Ohlendieck K, Matsumura K, Ionasescu V V, Towbin J A, Bosch E P, Weinstein S L, Sernett S W, Campbell K P
Howard Hughes Medical Institute, University of Iowa College of Medicine, Iowa City 52242.
Neurology. 1993 Apr;43(4):795-800. doi: 10.1212/wnl.43.4.795.
Dystrophin, the protein product of the Duchenne muscular dystrophy (DMD) gene, is a major component of the subsarcolemmal cytoskeleton and exists in a large oligomeric complex tightly associated with several sarcolemmal glycoproteins which provide a linkage to the extracellular matrix protein, laminin. In the present study, we investigated the status of the dystrophin-associated proteins in the skeletal muscle from 17 DMD patients of various ages. The results revealed a dramatic reduction in all of the dystrophin-associated proteins in the sarcolemma of DMD muscle compared with normal muscle and muscle from a variety of other neuromuscular diseases. This abnormality was common in all 17 DMD patients, irrespective of age. Our results indicate that the absence of dystrophin leads to the loss in all of the dystrophin-associated proteins, which renders DMD muscle fibers susceptible to necrosis. The analysis of dystrophin-associated proteins is important in the assessment of experimental therapies that attempt to replace dystrophin in DMD muscle.
肌营养不良蛋白是杜兴氏肌营养不良症（DMD）基因的蛋白质产物，是肌膜下细胞骨架的主要成分，存在于一个大型寡聚复合体中，该复合体与几种肌膜糖蛋白紧密相连，这些糖蛋白与细胞外基质蛋白层粘连蛋白形成连接。在本研究中，我们调查了17名不同年龄的DMD患者骨骼肌中肌营养不良蛋白相关蛋白的状态。结果显示，与正常肌肉以及来自各种其他神经肌肉疾病的肌肉相比，DMD肌肉肌膜中所有肌营养不良蛋白相关蛋白都显著减少。这种异常在所有17名DMD患者中都很常见，与年龄无关。我们的结果表明，肌营养不良蛋白的缺失导致所有肌营养不良蛋白相关蛋白的丧失，这使得DMD肌纤维易发生坏死。分析肌营养不良蛋白相关蛋白对于评估试图在DMD肌肉中替代肌营养不良蛋白的实验性疗法很重要。
