Lanju Xu, Jing Xu, Shichang Liu, Zhuo Yang
College of Medicine, Tianjin, 300060, China; CSPC The Institute of Pharmaceutical Research Shijiazhuang, Hebei, 050051, China.
J Appl Toxicol. 2014 Jun;34(6):651-7. doi: 10.1002/jat.2890. Epub 2013 Jul 19.
Antimycin A (AMA) is an inhibitor of mitochondrial electron transport chain via binding to mitochondrial complex III. This inhibition increases the production of reactive oxygen species (ROS). The aim of the present study was to investigate the effect of AMA on PC12 cells in vitro. Results of the nuclear morphology and the flow cytometer indicated that AMA efficiently induced PC12 cell apoptosis. Moreover, the levels of ROS and Ca(2+) increased in the early stage of cell apoptosis induced by AMA treatment. All of Ca(2+) chelators, L-type Ca(2+) channel blockers and inhibitors of Ca(2+) released from endoplasmic reticulum and ROS scavenger, were used in this experiment. It was found that the Ca(2+) chelators and ROS scavengers, in particular, could delay AMA-induced PC12 cell apoptosis. In conclusion, the present study found that AMA induced PC12 cell apoptosis through ROS and Ca(2+).
抗霉素A（AMA）通过与线粒体复合物III结合，是线粒体电子传递链的抑制剂。这种抑制作用会增加活性氧（ROS）的产生。本研究的目的是调查AMA对体外PC12细胞的影响。核形态学和流式细胞仪检测结果表明，AMA能有效诱导PC12细胞凋亡。此外，在AMA处理诱导的细胞凋亡早期，ROS和Ca(2+)水平升高。本实验使用了所有的Ca(2+)螯合剂、L型Ca(2+)通道阻滞剂以及内质网释放Ca(2+)的抑制剂和ROS清除剂。结果发现，Ca(2+)螯合剂和ROS清除剂，尤其是它们，能够延缓AMA诱导的PC12细胞凋亡。总之，本研究发现AMA通过ROS和Ca(2+)诱导PC12细胞凋亡。
