Escherichia coli Shiga toxins induce apoptosis in epithelial cells that is regulated by the Bcl-2 family
Escherichia coli Shiga toxins induce apoptosis in epithelial cells that is regulated by the Bcl-2 family
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DOI：
10.1152/ajpgi.2000.278.5.g811
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发表时间：
2000-05-01
影响因子：
4.5
通讯作者：
Sherman, PM
中科院分区：
文献类型：
--
作者：
Jones, NL;Islur, A;Sherman, PM
人类肠细胞缺乏神经酰胺三己糖苷（Gb（3）），即滋贺毒素-l（Stx 1）和滋贺毒素-a（Stx 2）的受体。因此，这些毒素在介导产滋贺毒素大肠杆菌感染期间的肠道疾病中的作用尚不清楚。本研究的目的是确定Stx 1和Stx 2是否诱导表达（HEp-2，Caco-2）或缺乏（T84）Gb（3）的上皮细胞凋亡，并表征Bcl-2家族的作用。Stx 1（12.5 ng/ml）在HEp-2（21.9 +/-7.9%vs.0.8 +/-0.3%，P = 0.01）和Caco-2（10.1 +/-1.2%vs.3.1 +/-0.4%，P = 0.006）细胞中均诱导凋亡，但在Gb（3）缺陷型T84细胞中不诱导凋亡。毒素介导的HEp-2细胞凋亡与促凋亡蛋白Bax的表达增强有关。抑制半胱天冬酶的激活阻止毒素刺激的细胞凋亡。此外，通过瞬时转染过表达Bcl-2可以阻止Stx 1刺激的细胞死亡。这些结果表明，大肠杆菌产生的滋贺毒素可能与大肠杆菌的毒性有关。大肠杆菌信号Gb（3）表达上皮细胞经历与Bax表达增强相关的凋亡，从而导致半胱天冬酶级联的激活。
Human intestinal cells lack globotriaosylceramide (Gb(3)), the receptor for Shiga toxin-l (Stx1) and Shiga toxin-a (Stx2). Therefore, the role of these toxins in mediating intestinal disease during infection with Shiga toxin-producing Escherichia coli is unclear. The aims of this study were to determine whether Stx1 and Stx2 induce apoptosis in epithelial cells expressing (HEp-2, Caco-2) or lacking (T84) Gb(3) and to characterize the role of the Bcl-2 family. Stx1 (12.5 ng/ml) induced apoptosis in both HEp-2 (21.9 +/- 7.9% vs. 0.8 +/- 0.3%, P = 0.01) and Caco-2 (10.1 +/- 1.2% vs. 3.1 +/- 0.4%, P = 0.006) cells but not in Gb(3)-deficient T84 cells. Toxin-mediated apoptosis of HEp-2 cells was associated with enhanced expression of the proapoptotic protein Bax. Inhibition of caspase activation prevented toxin-stimulated apoptosis. In addition, overexpression of Bcl-2 by transient transfection blocked Stx1-stimulated cell death. These findings indicate that Shiga toxins produced by E. coli signal Gb(3)-expressing epithelial cells to undergo apoptosis in association with enhanced Bax expression, thereby resulting in activation of the caspase cascade.