TY - JOUR
T1 - Shiga toxin 2 causes apoptosis in human brain microvascular endothelial cells via C/EBP homologous protein
AU - Fujii, Jim
AU - Wood, Katie
AU - Matsuda, Fumiko
AU - Carneiro-Filho, Benedito A.
AU - Schlegel, Keilo H.
AU - Yutsudo, Takashi
AU - Binnington-Boyd, Beth
AU - Lingwood, Clifford A.
AU - Obata, Fumiko
AU - Kim, Kwang S.
AU - Yoshida, Shin Ichi
AU - Obrig, Tom
PY - 2008/8
Y1 - 2008/8
N2 - 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.
AB - 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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U2 - 10.1128/IAI.01581-07
DO - 10.1128/IAI.01581-07
M3 - Article
C2 - 18541659
AN - SCOPUS:48849111923
SN - 0019-9567
VL - 76
SP - 3679
EP - 3689
JO - Infection and Immunity
JF - Infection and Immunity
IS - 8
ER -