Satoh Masahiko, Kaji Toshiyuki, Tohyama Chiharu
Gifu Pharmaceutical University 5-6-1, Mitahora-higashi, Gifu 502-8585, Japan.
Nihon Eiseigaku Zasshi. 2003 Jan;57(4):615-23. doi: 10.1265/jjh.57.615.
We have reviewed studies on cadmium (Cd) toxicity in laboratory animals and cultured cells with special attention to the disruption in cellular signal transduction, involvement in apoptosis of Cd, the cellular transport system for Cd and roles of metallothionein as a protective factor against Cd. Cd affects cellular functions by perturbing signal transductions, such as protein kinase C, mitogen-activated protein kinase and cyclic AMP pathways, but how the disruption of these pathways by Cd leads to the manifestation of toxicity in vivo is largely unknown. Exposure to cadmium at relatively high and low levels causes necrosis and apoptosis, respectively, which suggests that the mode of cell death by cadmium is dependent upon its exposure level. On the other hand, utilization of Ca2+ channels, DMT1 (divalent metal transporter 1) and a novel transport system having high-affinity for Mn2+ and Cd2+ were found to act as Cd transport systems via the cellular membrane. Metallothionein-I/II-null mice are highly susceptible to renal toxicity, hepatotoxicity, bone injury, hematotoxicity and immunotoxicity caused by chronic Cd exposure. Thus, metallothionein plays an important role in detoxification of Cd toxicity.
我们回顾了关于实验室动物和培养细胞中镉（Cd）毒性的研究，特别关注细胞信号转导的破坏、镉参与的细胞凋亡、镉的细胞转运系统以及金属硫蛋白作为镉保护因子的作用。镉通过干扰信号转导来影响细胞功能，如蛋白激酶C、丝裂原活化蛋白激酶和环磷酸腺苷途径，但镉对这些途径的破坏如何导致体内毒性表现，目前尚不清楚。相对高剂量和低剂量的镉暴露分别导致坏死和凋亡，这表明镉导致的细胞死亡方式取决于其暴露水平。另一方面，发现钙离子通道、二价金属转运体1（DMT1）以及对锰离子和镉离子具有高亲和力的新型转运系统可作为镉通过细胞膜的转运系统。金属硫蛋白-I/II基因敲除小鼠对慢性镉暴露引起的肾毒性、肝毒性、骨损伤、血液毒性和免疫毒性高度敏感。因此，金属硫蛋白在镉毒性解毒中起重要作用。
