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

被引：45

作者：

Fujii, Jun ^{[1
]}

Wood, Katie ^{[2
]}

Matsuda, Fumiko ^{[1
]}

Carneiro-Filho, Benedito A. ^{[3
]}

Schlegel, Keilo H. ^{[2
]}

Yutsudo, Takashi ^{[4
]}

Binnington-Boyd, Beth ^{[5
]}

Lingwood, Clifford A. ^{[5
]}

Obata, Fumiko

Kim, Kwang S. ^{[6
]}

Yoshida, Shin-ichi ^{[1
]}

Obrig, Tom ^{[2
]}

机构：

[1] Kyushu Univ, Grad Sch Med Sci, Dept Bacteriol, Fukuoka 8128582, Japan

[2] Univ Virginia, Dept Internal Med Nephrol, Charlottesville, VA 22908 USA

[3] Univ Virginia, Ctr Global Hlth, Dept Med, Charlottesville, VA 22908 USA

[4] Shionogi & Co Ltd, Discovery Res Lab, Mishima Scttsu City, Osaka 5660022, Japan

[5] Hosp Sick Children, Mol Struct & Funct Res Inst, Toronto, ON M5G 1X8, Canada

[6] Johns Hopkins Univ, Sch Med, Div Pediat Infect Dis, Baltimore, MD 21287 USA

来源：

INFECTION AND IMMUNITY | 2008年 / 76卷 / 08期

关键词：

D O I：

10.1128/IAI.01581-07

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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.

引用

页码：3679 / 3689

页数：11

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