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

Jun Fujii1, Katie Wood, Fumiko Matsuda

  • 1Department of Bacteriology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, 812-8582, Japan. junfujii@bact.med.kyushu-u.ac.jp.

Infection and Immunity
|June 11, 2008
PubMed

Insights

Shiga toxin 2 (Stx2) from E. coli O157 induces apoptosis in human brain microvascular endothelial cells (HBMEC) by activating caspases and upregulating CHOP. This study reveals CHOP

Area of Science:

  • Microbiology
  • Cell Biology
  • Toxicology

Background:

  • Shiga toxins (Stx1 and Stx2) from Escherichia coli O157 are cytotoxic, inhibiting protein synthesis and inducing apoptosis in various cell types.
  • The precise mechanisms by which Stx2 affects human brain microvascular endothelial cells (HBMEC) remain incompletely understood.

Purpose of the Study:

  • To investigate the role of Shiga toxin 2 (Stx2) in inducing apoptosis in HBMEC.
  • To identify key molecular mediators, such as C/EBP homologous protein (CHOP), involved in Stx2-induced apoptosis.

Main Methods:

  • Treatment of HBMEC with Stx2 and assessment of DNA fragmentation and caspase activation.
  • Microarray analysis to identify genes upregulated by Stx2.
  • CHOP mRNA knockdown to evaluate its role in apoptosis.

Main Results:

  • Stx2 treatment induced DNA fragmentation and activated caspases -3, -6, -8, and -9 in HBMEC.
  • Stx2 upregulated the expression of CHOP (also known as GADD153).
  • CHOP upregulation was dependent on enzymatically active Stx1, and CHOP knockdown inhibited caspase activation and prevented apoptosis.

Conclusions:

  • Stx2-induced apoptosis in HBMEC is mediated by CHOP.
  • The apoptotic process involves the activation of both intrinsic and extrinsic apoptotic pathways.

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