Mechanism of Clostridium difficile toxin A-induced apoptosis in T84 cells

被引:97
|
作者
Brito, GAC
Fujji, J
Carneiro, BA
Lima, AAM
Obrig, T
Guerrant, RL
机构
[1] Univ Virginia, Dept Internal Med, Charlottesville, VA 22908 USA
[2] Univ Fed Ceara, Dept Morphol, Univ Hosp, Fortaleza, Ceara, Brazil
[3] Univ Fed Ceara, Inst Biomed, Univ Hosp, Fortaleza, Ceara, Brazil
[4] Univ Fed Ceara, Clin Res Unit, Univ Hosp, Fortaleza, Ceara, Brazil
来源
JOURNAL OF INFECTIOUS DISEASES | 2002年 / 186卷 / 10期
关键词
D O I
10.1086/344729
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
This study is an investigation into the mechanism of Clostridium difficile toxin A-induced apoptosis in human intestinal epithelial cells. Toxin A induced apoptosis of T84 cells in a dose- and time-dependent fashion. Toxin A-induced apoptosis was completely inhibited by blocking toxin enzymatic activity on Rho GTPases with uridine 5'-diphosphate-2,3-dialdehyde by a nonspecific caspase inhibitor and was partially inhibited by caspase-1, -3, -6, -8, and -9 inhibitors. Caspases 3, 6, 8, and 9 and Bid activation were detected. Toxin A also induced changes in mitochondrial membrane potential and cytochrome c release at 18-24 h, a time course similar to caspase-9 activation. In conclusion, toxin A induces apoptosis by a mechanism dependent on inactivation of Rho, activation of caspases 3, 6, 8, and 9 and Bid, and mitochondrial damage followed by cytochrome c release. Toxin A proapoptotic activity may contribute to the mucosal disruption seen in toxin A-induced enteritis.
引用
收藏
页码:1438 / 1447
页数:10
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