Belyaeva Elena A, Saris Nils-Erik L
Laboratory of Comparative Biochemistry of Inorganic Ions, Sechenov Institute of Evolutionary Physiology and Biochemistry of Russian Academy of Sciences, Thorez Avenue 44 St. Petersburg 194223, Russia.
Biochem Res Int. 2011;2011:387297. doi: 10.1155/2011/387297. Epub 2011 Jul 14.
Mitochondria of AS-30D rat ascites hepatoma cells are found to be the main target for Zn(2+) and sodium selenite (Na(2)SeO(3)). High [mu]M concentrations of Zn(2+) or selenite were strongly cytotoxic, killing the AS-30D cells by both apoptotic and necrotic ways. Both Zn(2+) and selenite produced strong changes in intracellular generation of reactive oxygen species (ROS) and the mitochondrial dysfunction via the mitochondrial electron transport chain (mtETC) disturbance, the membrane potential dissipation, and the mitochondrial permeability transition pore opening. The significant distinctions in toxic action of Zn(2+) and selenite on AS-30D cells were found. Selenite induced a much higher intracellular ROS level (the early event) compared to Zn(2+) but a lower membrane potential loss and a lower decrease of the uncoupled respiration rate of the cells, whereas the mtETC disturbance was the early and critical event in the mechanism of Zn(2+) cytotoxicity. Sequences of events manifested in the mitochondrial dysfunction produced by the metal/metalloid under test are compared with those obtained earlier for Cd(2+), Hg(2+), and Cu(2+) on the same model system.
研究发现，AS-30D大鼠腹水肝癌细胞的线粒体是锌离子（Zn(2+)）和亚硒酸钠（Na(2)SeO(3)）的主要作用靶点。高微摩尔浓度的Zn(2+)或亚硒酸盐具有很强的细胞毒性，通过凋亡和坏死两种方式杀死AS-30D细胞。Zn(2+)和亚硒酸盐都会通过干扰线粒体电子传递链（mtETC）、耗散膜电位以及打开线粒体通透性转换孔，使细胞内活性氧（ROS）生成和线粒体功能发生显著变化。研究发现Zn(2+)和亚硒酸盐对AS-30D细胞的毒性作用存在显著差异。与Zn(2+)相比，亚硒酸盐诱导的细胞内ROS水平更高（早期事件），但膜电位损失更低，细胞解偶联呼吸速率下降也更低，而mtETC干扰是Zn(2+)细胞毒性机制中的早期关键事件。将受试金属/类金属导致的线粒体功能障碍所表现出的事件顺序，与之前在同一模型系统上获得的镉离子（Cd(2+)）、汞离子（Hg(2+)）和铜离子（Cu(2+)）的相关结果进行了比较。
