The cell biological hypothesis of Duchenne muscular dystrophy assumes that deficiency in the membrane cytoskeletal element dystrophin triggers a loss in surface glycoproteins, such as beta-dystroglycan, thereby rendering the sarcolemmal membrane more susceptible to micro-rupturing. Secondary changes in ion homeostasis, such as increased cytosolic Ca2+ levels and impaired luminal Ca2+ buffering, eventually lead to Ca2+-induced myonecrosis. However, individual muscle groups exhibit a graded pathological response during the natural time course of x-linked muscular dystrophy. The absence of the dystrophin isofom Dp427 does not necessarily result in a severe dystrophic phenotype in all muscle groups. In the dystrophic mdx animal model, extraocular and toe muscles are not as severely affected as limb muscles. Here, we show that the relative expression and sarcolemmal localization of the central trans-sarcolemmal linker of the dystrophin-glycoprotein complex, beta-dystroglycan, is preserved in mdx extraocular and toe fibres by means of two-dimensional immunoblotting and immunofluorescence microscopy. Thus, with respect to improving myology diagnostics, the relative expression levels of beta-dystroglycan appear to represent reliable markers for the severity of secondary changes in dystrophin-deficient fibres. Immunoblotting and enzyme assays revealed that mdx toe muscle fibres exhibit an increased expression and activity of the sarcoplasmic reticulum Ca2+-ATPase. Chemical crosslinking studies demonstrated impaired calsequestrin oligomerization in mdx gastrocnemius muscle indicating that abnormal calsequestrin clustering is involved in reduced Ca2+ buffering of the dystrophic sarcoplasmic reticulum. Previous studies have mostly attributed the sparing of certain mdx fibres to the special protective properties of small-diameter fibres. Our study suggests that the rescue of dystrophin-associated glycoproteins, and possibly the increased removal of cytosolic Ca2+ ions, might also play an important role in protecting muscle cells from necrotic changes.

中文翻译：

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Dp427缺陷的mdx组织的比较分析表明，眼外和脚趾肌纤维的营养不良表型较轻，与β-营养不良聚糖的持续表达有关。

杜兴氏肌营养不良症的细胞生物学假设认为，膜细胞骨架成分肌营养不良蛋白的缺乏会触发表面糖蛋白（例如β-营养不良聚糖）的损失，从而使肌膜更易发生微破裂。离子稳态的继发变化，例如胞质Ca2 +水平增加和管腔Ca2 +缓冲液受损，最终导致Ca2 +引起的心肌坏死。但是，在x连锁肌营养不良症的自然过程中，单个肌肉群表现出分级的病理反应。肌营养不良蛋白等蛋白Dp427的缺乏不一定会在所有肌肉组中导致严重的营养不良表型。在营养不良的mdx动物模型中，眼外和脚趾肌肉受到的影响不如肢体肌肉严重。这里，我们表明，通过二维免疫印迹和免疫荧光显微镜检查，肌营养不良蛋白-糖蛋白复合物，β-肌营养不良蛋白的中央反肌膜连接子的相对表达和肌膜定位被保存在mdx眼外和脚趾纤维中。因此，就改善肌病学诊断而言，β-dystroglycan的相对表达水平似乎代表了肌营养不良蛋白缺陷纤维继发性变化严重程度的可靠标志。免疫印迹和酶法测定显示，mdx趾肌纤维显示出肌浆网Ca2 + -ATPase的表达和活性增加。化学交联研究表明，mdx腓肠肌中的Calsequestrin寡聚化受损，表明Calsequestrin聚集异常与营养不良性肌浆网的Ca2 +缓冲液减少有关。先前的研究主要将某些mdx纤维的稀少归因于小直径纤维的特殊保护性能。我们的研究表明，肌营养不良蛋白相关糖蛋白的抢救，以及可能增加的胞浆Ca2 +离子去除，也可能在保护肌肉细胞免受坏死变化中起重要作用。