Elevation of vacuolar pH inhibits the cytotoxic activity of furin-cleaved exotoxin A.
Elevation of vacuolar pH inhibits the cytotoxic activity of furin-cleaved exotoxin A.
复制标题
液泡 pH 值升高会抑制弗林蛋白酶裂解的外毒素 A 的细胞毒活性。
DOI：
10.1128/iai.65.6.2240-2242.1997
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发表时间：
1997
影响因子：
3.1
通讯作者：
Draper,RK
中科院分区：
文献类型：
--
作者：
Corboy,MJ;Draper,RK
外毒素A（ETA）通过一个涉及受体介导的内吞作用和37 kDa蛋白水解片段跨膜转运到细胞质中的过程抑制细胞中的蛋白质合成。该片段显然是在毒素被内吞后由内切蛋白酶弗林蛋白酶产生的。通过弗林蛋白酶切割ETA需要体外低pH，并且推测也需要体内低pH。已知提高细胞内区室pH值的药物可以保护细胞免受ETA的侵害。解释这种保护作用的最简单的假设是药物干扰弗林蛋白酶裂解。为了验证这个想法，我们测量了pH升高药物对ETA作用的影响，ETA在加入细胞之前已经用重组弗林蛋白酶预处理过。令人惊讶的是，我们发现pH升高药物可以保护细胞免受预切割的ETA以及完整的ETA。这些结果表明，ETA中毒细胞的过程需要一个低的液泡pH值的另一个事件，除了弗林蛋白酶的蛋白水解。
Exotoxin A (ETA) inhibits protein synthesis in cells by a process that involves receptor-mediated endocytosis and the transport of a 37-kDa proteolytic fragment across a membrane into the cytoplasm. The fragment is apparently generated by the endoprotease furin after the toxin has been endocytosed. Cleavage of ETA by furin requires a low pH in vitro, and presumably also in vivo. Drugs that raise the pH of intracellular compartments are known to protect cells from ETA. The simplest hypothesis to explain this protection has been that the drugs interfere with furin cleavage. To test this idea, we measured the effect of pH-elevating drugs on the action of ETA that had been precleaved with recombinant furin before addition to cells. Surprisingly, we found that pH-elevating drugs protected cells from precleaved ETA as well as intact ETA. These results suggest that the process by which ETA intoxicates cells requires a low vacuolar pH for another event in addition to proteolysis by furin.