T-2 toxin initially activates caspase-2 and induces apoptosis in U937 cells
T-2 toxin initially activates caspase-2 and induces apoptosis in U937 cells
复制标题
DOI：
10.1016/j.toxlet.2006.05.017
复制
发表时间：
2007-04-05
影响因子：
3.5
通讯作者：
Morimoto, Kanehisa
中科院分区：
文献类型：
--
作者：
Huang, Peixin;Akagawa, Keisuke;Morimoto, Kanehisa
T-2毒素是镰刀菌合成的一组真菌毒素，是一种常见的天然污染物，能诱导U937细胞凋亡，具有独特的形态学和生物学特征。浓度超过10 nM的T-2毒素影响细胞活力，诱导细胞核和DNA片段化以及caspase-3活化。Caspase-2、-3、-8和-9在T-2毒素诱导的细胞凋亡过程中被激活。T-2毒素既不抑制线粒体呼吸链复合物I-IV在分离的线粒体，也不降低ATP水平在U937细胞。酶活性测定和Western blot分析均显示T-2毒素激活caspase-2的时间早于caspase-3、-8和-9。Caspase-2抑制剂（VDVAD-CHO/fcase 2）和Caspase-8抑制剂（IETD-CHO/fcase 8）可完全阻断T-2毒素诱导的caspase-3前体蛋白的表达，而Caspase-9抑制剂（LEHD-CHO/fcase 9）的阻断效果较差。Caspase-2抑制剂完全阻断T-2毒素诱导的caspase-8和-9活化。这些结果清楚地表明，caspase-2的激活是必不可少的T-2毒素诱导的细胞凋亡，凋亡信号主要是通过caspase-8和caspase-3，而不是线粒体途径。(C)2007爱思唯尔爱尔兰有限公司保留所有权利。
T-2 toxin, which belongs to a group of mycotoxins synthesized by Fusarium fungi that are widely encountered as natural contaminants, induced apoptosis with distinct morphological and biological features in U937 cells. The concentration of more than 10 nM T-2 toxin affected cell viability, induced nuclear and DNA fragmentation and caspase-3 activation. Caspase-2, -3, -8, and -9 were activated during T-2 toxin-induced apoptosis. T-2 toxin neither inhibited mitochondrial respiratory chain complexes I-IV in isolated mitochondria nor decreased ATP levels in U937 cells. Both enzyme activity assay and Western blot analysis revealed that T-2 toxin activated caspase-2 earlier than caspase-3, -8, and -9. Caspase-2 inhibitor (VDVAD-CHO/fmk) and caspase-8 inhibitor (IETD-CHO/fmk) completely blocked the T-2 toxin-induced process of procaspase-3, while caspase-9 inhibitor (LEHD-CHO/fmk) did so less effectively. Caspase-2 inhibitor entirely blocked T-2 toxin-induced caspase-8, and -9 activation. These results clearly indicate that activation of caspase-2 is essential to T-2 toxin-induced apoptosis and that apoptotic signals are mainly transmitted via caspase-8 and caspase-3 rather than mitochondrial pathway. (C) 2007 Elsevier Ireland Ltd. All rights reserved.