Shiga toxin 2 causes apoptosis in human brain microvascular endothelial cells via C/EBP homologous protein

Jim Fujii*, Katie Wood, Fumiko Matsuda, Benedito A. Carneiro-Filho, Keilo H. Schlegel, Takashi Yutsudo, Beth Binnington-Boyd, Clifford A. Lingwood, Fumiko Obata, Kwang S. Kim, Shin Ichi Yoshida, Tom Obrig

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

44 Scopus citations

Abstract

Shiga toxin 1 (Stx1) and Stx2 produced by Escherichia coli O157 are known to be cytotoxic to Vero and HeLa cells by inhibiting protein synthesis and by inducing apoptosis. In the present study, we have demonstrated that 10 ng/ml Stx2 induced DNA fragmentation in human brain microvascular endothelial cells (HBMEC), with cleavage activation of caspase-3, -6, -8, and -9. A microarray approach used to search for apoptotic potential signals in response to Stx2 revealed that Stx2 treatment induced a marked upregulation of C/EBP homologous protein (CHOP)/growth arrest and DNA damage-inducible protein 153 (GADD153). Increased CHOP expression was dependent on enzymatically active Stx1. Knockdown of CHOP mRNA reduced the activation of caspase-3 and prevented apoptotic cell death. These results suggest that Stx2-induced apoptosis is mediated by CHOP in HBMEC and involves activation of both the intrinsic and extrinsic pathways of apoptosis.

Original languageEnglish (US)
Pages (from-to)3679-3689
Number of pages11
JournalInfection and immunity
Volume76
Issue number8
DOIs
StatePublished - Aug 2008

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

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