Trichothecin induces apoptosis of HepG2 cells via caspase-9 mediated activation of the mitochondrial death pathway
Trichothecin induces apoptosis of HepG2 cells via caspase-9 mediated activation of the mitochondrial death pathway
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单端孢菌素通过 caspase-9 介导的线粒体死亡途径激活诱导 HepG2 细胞凋亡
DOI：
10.1016/j.toxicon.2011.11.003
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发表时间：
2012-01-01
期刊：
影响因子：
2.8
通讯作者：
Tan, Ren Xiang
中科院分区：
文献类型：
--
作者：
Du, Rong Hui;Cui, Jiang Tao;Tan, Ren Xiang
单端孢菌素是一种广泛存在于食品和环境中的真菌毒素，严重威胁着人类和动物的健康。已经表明，喜树碱改变了细胞线粒体的形态。然而，其分子机制仍然未知。在这里，我们发现，细胞活力减弱的喜树碱。细胞凋亡的特点，如同源凝集和核小体间的碎裂。在mRNA水平上，抗凋亡蛋白Bcl-2表达减少，促凋亡蛋白Bax表达增强，与细胞凋亡率升高一致。此外，caspase-9的表达和caspase-3的活性增加后，处理后的喜树碱。因此，线粒体膜电位（Δ Psi m）以剂量依赖性方式降低。结果表明，胞浆内Ca 2+浓度升高，胞浆内活性氧（reactive oxygen species，ROS）增加。综上所述，我们的研究结果表明，喜树碱诱导的细胞凋亡是通过激活caspase-9介导的，线粒体功能的下降是由于钙超载和ROS产生。(C)2011爱思唯尔有限公司保留所有权利。
Trichothecin, one of fungal toxins which were encountered in food and in the environment, seriously threatens human and animal health. It has been shown that trichothecin changed the morphology of cellular mitochondria. However, the molecular mechanism remains unknown. Here we found that cell viability was attenuated by trichothecin. Features of apoptosis such as homosomal condensation and inter nucleosomal fragmentation were observed. In consistence with the elevated apoptosis rate, expression of antiapoptotic protein Bcl-2 was diminished and expression of proapoptotic protein Bax was enhanced at mRNA levels. Furthermore, expression of caspase-9 and activity of caspase-3 were increased after the treatment of trichothecin. Accordingly, the mitochondrial membrane potential (Delta Psi m) was decreased in a dose-dependent manner. And Ca2+ overload was induced by trichothecin, followed by the generation of reactive oxygen species (ROS). Collectedly, our results suggested that apoptosis induced by trichothecin is mediated by caspase-9 activation and the decrement of mitochondrial function resulted from the overloaded calcium and ROS production. (C) 2011 Elsevier Ltd. All rights reserved.