Muscle fibre breakdown in venom-induced muscle degeneration
Muscle fibre breakdown in venom-induced muscle degeneration
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DOI：
10.1046/j.1469-7580.2003.00171.x
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发表时间：
2003-04-01
影响因子：
2.4
通讯作者：
Cullen, MJ
中科院分区：
文献类型：
--
作者：
Harris, JB;Vater, R;Cullen, MJ
我们研究了骨骼肌退化的早期阶段，使用Notechis scutatus的毒液作为肌肉毒性剂。毒液的使用剂量相当于小鼠的LD 50。大鼠中无死亡。电子显微镜被用来显示进行性过度收缩的肌节和个别肌纤维中的肌原纤维排列的损失。在过度收缩的区域之间，肌节被撕裂，松散的肌丝脱落到细胞质中。免疫印迹和考马斯染色用于比较结蛋白、肌联蛋白、肌动蛋白、肌球蛋白和肌营养不良蛋白的各自损失率。我们发现，结蛋白和肌联蛋白是第一个蛋白质被降解的时间约为1小时和3小时，分别为50%的损失。主要的收缩蛋白，肌球蛋白和肌动蛋白的损失，是相当缓慢的。肌营养不良蛋白的丢失也比结蛋白和肌联蛋白的丢失慢。肌纤维质膜的早期损伤引起细胞脱钙，可能促进肌节的过度收缩，但即使在24小时，膜的实际损失也是不完全的。我们认为，结蛋白和肌联蛋白的早期降解是负责肌节的解聚;释放的收缩蛋白肌球蛋白和肌动蛋白脱落到胞质溶胶中，在那里它们被降解。吞噬细胞侵入退化的肌纤维，主要参与清除受损的线粒体。
We studied the early stages of the degeneration of skeletal muscles using the venom of Notechis scutatus as the myotoxic agent. The venom was used at a dose equivalent to the LD50 in the mouse. There was no mortality amongst the rats. Electron microscopy was used to show the progressive hypercontraction of sarcomeres and the loss of alignment of myofibrils in individual muscle fibres. Between areas of hypercontraction sarcomeres were torn, shedding loosened myofilaments into the cytosol. Western blotting and Coomassie staining were used to compare the respective rates of loss of desmin, titin, actin, myosin and dystrophin. We showed that desmin and titin were the first proteins to be degraded with a time to 50% loss of approximately 1 h and 3 h, respectively. The loss of major contractile proteins, myosin and actin, was rather slower. The loss of dystrophin was also slower than the loss of desmin and titin. Early damage to the plasma membrane of the muscle fibre caused the cells to depolarize, probably promoting the hypercontraction of the sarcomeres, but actual loss of membrane was incomplete even at 24 h. We suggest that the early degradation of desmin and titin was responsible for the disaggregation of the sarcomeres; the liberated contractile proteins myosin and actin were shed into the cytosol, where they were degraded. Phagocytic cells that had invaded the degenerating muscle fibres were primarily involved in the clearance of damaged mitochondria.