Escherichia coli Shiga toxins induce apoptosis in epithelial cells that is regulated by the Bcl-2 family Academic Article uri icon

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abstract

  • Human intestinal cells lack globotriaosylceramide (Gb3), the receptor for Shiga toxin-1 (Stx1) and Shiga toxin-2 (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) Gb3 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 Gb3-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 Gb3-expressing epithelial cells to undergo apoptosis in association with enhanced Bax expression, thereby resulting in activation of the caspase cascade.

authors

  • Jones, Nicola L
  • Islur, Avinash
  • Haq, Rizwan
  • Mascarenhas, Mariola
  • Karmali, Mohamed A
  • Perdue, Mary
  • Zanke, Brent W
  • Sherman, Philip M

publication date

  • May 1, 2000

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