Open AccessShiga Toxin 2 Causes Apoptosis in Human Brain Microvascular Endothelial Cells via C/EBP Homologous Protein
Author(s) -
Jun Fujii,
Katie Wood,
Fumiko Matsuda,
Benedito A. CarneiroFilho,
Keilo H. Schlegel,
Takashi Yutsudo,
Beth Binnington-Boyd,
Clifford A. Lingwood,
Fumiko Obata,
Kwang S. Kim,
Shin-ichi Yoshida,
Tom G. Obrig
Publication year - 2008
Publication title -
infection and immunity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.508
H-Index - 220
eISSN - 1070-6313
pISSN - 0019-9567
DOI - 10.1128/iai.01581-07
Subject(s) - apoptosis , biology , dna fragmentation , shiga toxin , chop , microbiology and biotechnology , shiga like toxin , gene knockdown , fragmentation (computing) , downregulation and upregulation , programmed cell death , escherichia coli , biochemistry , gene , ecology
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.
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