Pathogenesis of Shigella diarrhea. VIII. Evidence for a translocation step in the cytotoxic action of Shiga toxin.
Pathogenesis of Shigella diarrhea. VIII. Evidence for a translocation step in the cytotoxic action of Shiga toxin.
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志贺氏菌腹泻的发病机制。
DOI：
10.1093/infdis/148.5.844
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发表时间：
1983
期刊：
影响因子：
--
通讯作者：
Keusch,GT
中科院分区：
文献类型：
--
作者：
Jacewicz,M;Keusch,GT
志贺氏菌毒素通过与糖蛋白细胞表面受体结合与HeLa细胞相互作用，并且在滞后期后，使60 S核糖体亚基失活并抑制蛋白质合成。滞后期可能是由于能量依赖性的毒素转移到细胞内部。这一步是用已知抑制葡萄糖代谢、线粒体能量产生或大分子合成的药物和改变细胞骨架系统或溶酶体的药物进行研究的。代谢抑制剂降低了毒素的细胞毒性和结合。除放线菌素D外，所有测试药物也减少了内吞作用。在膜透化剂二甲基亚砜的存在下，对细胞毒性的影响部分逆转。各种细胞松弛素、秋水仙碱、长春花生物碱、氯喹和类固醇也降低了毒素的活性。这些不同的代理商可能会影响志贺氏菌毒素的内化和/或细胞内加工的共同途径。这种毒素的转运显然是通过细胞表面的内吞作用发生的。
Shigella toxin interacts with HeLa cells by binding to a glycoprotein cell surface receptor and, after a lag period, inactivates the 60Sribosomal subunit and inhibits protein synthesis. The lag period may be due to energy-dependent translocation of the toxin to the interior of the cells. This step was investigated with agents known to inhibit glucose metabolism, mitochondrial energy production, or macromolecular synthesis and with drugs that alter the cytoskeletal system or lysosomes. Metabolic inhibitors reduced both cytotoxicity and binding of the toxin. All agents tested except actinomycin D also diminished endocytosis. Effects on cytotoxicity were partially reversed in the presence of the membrane permeabilizer dimethylsulfoxide. Various cytochalasins, colchicine, vinca alkaloids, chloroquine, and steroids also reduced the activity of the toxin. These diverse agents are probably acting on a common pathway affecting the internalization and/or intracellular processing of shigella toxin. Translocation of this toxin apparently occurs by endocytosis from the cell surface.