Proteasome expression in the skeletal muscles of patients with muscular dystrophy
Proteasome expression in the skeletal muscles of patients with muscular dystrophy
复制标题
DOI：
10.1007/s004010000229
复制
发表时间：
2000-12-01
影响因子：
12.7
通讯作者：
Tsuda, T
中科院分区：
文献类型：
--
作者：
Kumamoto, T;Fujimoto, S;Tsuda, T
以前的研究人员认为，钙蛋白酶，钙依赖性蛋白酶的蛋白水解，导致肌纤维降解杜氏和贝克肌营养不良症（DMD/BMD）。最近的证据表明，非溶酶体ATP-泛素依赖性蛋白水解复合物（蛋白酶体）参与肌肉萎缩在各种分解代谢状态和肌纤维降解的生理或病理条件。为了阐明蛋白酶体在营养不良肌肉中的可能作用，对从各种神经肌肉疾病患者（包括DMD/BMD、多发性肌炎（PM）、肌萎缩性侧索硬化和周围神经病）和正常人肌肉标本中获得的肌肉活检标本进行26 S蛋白酶体的常规组织化学和免疫组织化学。免疫组化显示，正常人肌肉中蛋白酶体定位于细胞质中，但染色强度较弱。与对照肌肉相比，蛋白酶体和泛素的异常增加主要表现在坏死纤维的细胞质中，在DMD/BMD和PM中再生纤维的程度较低。非坏死，萎缩的纤维在所有患病的肌肉表现出中度或弱的免疫反应的蛋白质，其染色强度比对照肌纤维强。这两种蛋白质通常共定位良好。并不是所有的肌营养不良蛋白缺乏的肌纤维表现出强烈的反应蛋白酶体。我们的研究结果显示，DMD/ PMD的坏死和再生肌纤维中的蛋白酶体增加，尽管这可能不是疾病特异性上调。我们认为，ATP-泛素依赖的蛋白水解途径以及非溶酶体钙蛋白酶途径可能参与肌营养不良症的肌纤维降解。
Previous investigators have suggested that proteolysis by calpain, a Ca2+-dependent protease, causes muscle fiber degradation in Duchenne and Becker muscular dystrophies (DMD/BMD). Recent evidence indicates that the nonlysosomal ATP-ubiquitin-dependent proteolytic complex (proteasomes) participates in muscle wasting during various catabolic states and in muscle fiber degradation in physiological or pathological conditions. To elucidate the possible role of proteasomes in dystrophic muscles, routine histochemistry and immunohistochemistry of 26S proteasomes were performed on muscle biopsy specimens obtained from patients with various neuromuscular disorders including DMD/BMD, polymyositis (PM), amyotrophic lateral sclerosis, and peripheral neuropathies, and on normal human muscle specimens. Immunohistochemically, proteasomes were located in the cytoplasm in normal human muscle, but their staining intensity was faint. Compared to control muscles, abnormal increases in both proteasomes and ubiquitin were demonstrated mainly in the cytoplasm of necrotic fibers and to a lesser extent in regenerative fibers in DMD/BMD and PM. Non-necrotic, atrophic fibers in all diseased muscles showed moderate or weak immunoreactions for the proteins; their staining intensities were stronger than those of control muscle fibers. Both proteins often colocalized well. Not all dystrophin-deficient muscle fibers showed a strong reaction for proteasomes. Our results showed increased proteasomes in necrotic and regenerative muscle fibers in DMD/ PMD, although this may not be disease-specific up-regulation. We suggest that the ATP-ubiquitin-dependent proteolytic pathway as well as the nonlysosomal calpain pathway may participate in muscle fiber degradation in muscular dystrophy.