Cytolethal distending toxin induces caspase-dependent and -independent cell death in MOLT-4 cells

被引:22
作者
Ohara, Masaru [1 ]
Hayashi, Tomonori [2 ]
Kusunoki, Yoichiro [2 ]
Nakachi, Kei [2 ]
Fujiwara, Tamaki [1 ]
Komatsuzawa, Hitoshi [1 ]
Sugai, Motoyuki [1 ]
机构
[1] Hiroshima Univ, Grad Sch Biomed Sci, Dept Bacteriol, Minami Ku, Hiroshima 7348553, Japan
[2] Radiat Effects Res Fdn, Dept Radiobiol & Mol Epidemiol, Minami Ku, Hiroshima 7320815, Japan
关键词
D O I
10.1128/IAI.01612-07
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Cytolethal distending toxin (CDT) induces apoptosis using the caspase-dependent classical pathway in the majority of human leukemic T cells (MOLT-4). However, we found the process to cell death is only partially inhibited by pretreatment of the cells with a general caspase inhibitor, z-VAD-fmk. Flow cytometric analysis using annexin V and propidium iodide showed that a 48-h CDT treatment decreased the living cell population by 35% even in the presence of z-VAD-fmk. z-VAD-fmk completely inhibited caspase activity in 24 h CDT-intoxicated cells. Further, CDT with z-VAD-fmk treatment clearly increased the cell population that had a low level of intracellular reactive oxygen. This is a characteristic opposite to that of caspase-dependent apoptosis. Overexpression of bcl2 almost completely inhibited cell death using CDT treatment in the presence of z-VAD-fmk. The data suggest there are at least two different pathways used in CDT-induced cell death: conventional caspase-dependent (early) apoptotic cell death and caspase-independent (late) death. Both occur via the mitochondrial membrane disruption pathway.
引用
收藏
页码:4783 / 4791
页数:9
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