Din W S, Frazier J M
Biochem J. 1985 Sep 1;230(2):395-402. doi: 10.1042/bj2300395.
An isolated rat hepatocyte preparation was used to study the cellular toxicity of cadmium and the protective effects of metallothionein on cadmium-induced toxicity. Exposure of primary suspension cultures of isolated rat hepatocytes to Cd2+ (0-35.7 microM) for 15 min resulted in a dose-dependent reduction in the synthesis of cellular proteins during a subsequent 6 h incubation. Such inhibition could not be correlated with cellular lethality or gross membrane damage. Pre-induction of metallothionein in hepatocytes by zinc treatment in vivo of donor rats protected hepatocytes in vitro from cadmium-induced inhibition of protein synthesis. The protective effects in zinc-pre-induced hepatocytes are not due to alterations in the level of total cellular cadmium, but could be accounted for by the redistribution of intracellular cadmium in the presence of high levels of zinc-metallothionein. The data suggest that metallothionein exerts its protective effect by a kinetic detoxification mechanism, i.e. a decrease in reactive intracellular cadmium.
采用分离的大鼠肝细胞制剂来研究镉的细胞毒性以及金属硫蛋白对镉诱导毒性的保护作用。将分离的大鼠肝细胞原代悬浮培养物暴露于Cd2+（0 - 35.7微摩尔）15分钟，在随后6小时的孵育过程中，细胞蛋白质合成呈剂量依赖性减少。这种抑制作用与细胞致死率或明显的膜损伤无关。通过对供体大鼠进行体内锌处理来预先诱导肝细胞中的金属硫蛋白，可保护体外肝细胞免受镉诱导的蛋白质合成抑制。锌预先诱导的肝细胞中的保护作用并非由于细胞内镉总量水平的改变，而是可以由在高水平锌 - 金属硫蛋白存在下细胞内镉的重新分布来解释。数据表明，金属硫蛋白通过动力学解毒机制发挥其保护作用，即细胞内活性镉减少。
