Cloned Shiga Toxin 2 B Subunit Induces Apoptosis in Ramos Burkitt's Lymphoma B Cells
Cloned Shiga Toxin 2 B Subunit Induces Apoptosis in Ramos Burkitt's Lymphoma B Cells
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克隆志贺毒素 2 B 亚基诱导 Ramos Burkitt 淋巴瘤 B 细胞凋亡
DOI：
10.1128/iai.71.8.4828.2003
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发表时间：
2003
影响因子：
3.1
通讯作者：
G. Armstrong
中科院分区：
文献类型：
--
作者：
P. Marcato;George L. Mulvey;G. Armstrong
志贺滋贺毒素（Stx 1和Stx 2）由1型志贺菌和肠出血性大肠杆菌产生，由1个A亚基和5个B亚基组成。Stx 1和Stx 2 B亚基形成五聚体结构，其结合真核细胞上的神经酰胺三己糖苷（Gb 3-Cer）受体并促进内吞作用。然后A亚基抑制蛋白质的生物合成，从而引发受影响细胞的凋亡。除了其Gb 3-Cer结合活性之外，以下报告中的数据证明Stx 2 B五聚体独立于A亚基活性诱导拉莫斯Burkitt淋巴瘤B细胞中的细胞凋亡。在竞争性抑制Stx 2 B五聚体介导的细胞凋亡的Stx 1 B五聚体的无A亚基制剂中未观察到细胞凋亡。泛胱天蛋白酶抑制剂Z-VAD-fastin可防止暴露于Stx 2 B亚基、Stx 1或Stx 2的拉莫斯细胞的凋亡。布雷菲德菌素A，一种高尔基体转运系统的抑制剂，也阻止了Stx 2 B亚基介导的细胞凋亡。这些观察结果表明，Stx 2 B亚基必须通过Gb 3-Cer受体内化，以诱导拉莫斯细胞凋亡。此外，与两种全毒素不同，Stx 2 B亚基介导的细胞凋亡不涉及蛋白质生物合成的抑制。这项研究提供了进一步的洞察致病潜力，这个家庭的有效的细菌外毒素。
The Shiga toxins (Stx1 and Stx2), produced by Shigella dysenteriae type 1 and enterohemorrhagic Escherichia coli, consist of one A subunit and five B subunits. The Stx1 and Stx2 B subunits form a pentameric structure that binds to globotriaosylceramide (Gb3-Cer) receptors on eukaryotic cells and promotes endocytosis. The A subunit then inhibits protein biosynthesis, which triggers apoptosis in the affected cell. In addition to its Gb3-Cer binding activity, the data in the following report demonstrate that the Stx2 B pentamer induces apoptosis in Ramos Burkitt's lymphoma B cells independently of A subunit activity. Apoptosis was not observed in A subunit-free preparations of the Stx1 B pentamer which competitively inhibited Stx2 B pentamer-mediated apoptosis. The pancaspase inhibitor, Z-VAD-fmk, prevented apoptosis in Ramos cells exposed to the Stx2 B subunit, Stx1 or Stx2. Brefeldin A, an inhibitor of the Golgi transport system, also prevented Stx2 B subunit-mediated apoptosis. These observations suggest that the Stx2 B subunit must be internalized, via Gb3-Cer receptors, to induce Ramos cell apoptosis. Moreover, unlike the two holotoxins, Stx2 B subunit-mediated apoptosis does not involve inhibition of protein biosynthesis. This study provides further insight into the pathogenic potential of this family of potent bacterial exotoxins.