Elucidation of the mechanism of membrane transport, metallochaperone of essential trace metals related to central nervous activities

在本研究中，我们打算澄清微量金属的代谢，影响中枢神经系统的活动。用各种培养的细胞，我们研究了铜的金属伴侣，CCS，Cu，Zn-SOD，其中接受铜从CCS，和Ctr 1，这是铜转运蛋白在铜缺乏和过多的状态下的变化。在铜缺乏状态下，CCS和Cu，Zn-SOD的蛋白质含量增加。另一方面，在铜过多的状态下，CCS和Cu，Zn-SOD的蛋白质量表现出显著的下降。此外，我做了一个动物有太多的锌摄入量。在具有过多锌的状态下，发生肠道中的铜吸收障碍。提示肠道细胞中的铜减少，铜转运蛋白ATP 7A也减少，在神经细胞来源的培养细胞中添加铜螯合物，细胞中的花生四烯酸代谢发生变化。铜缺乏导致Cu，Zn-SOD活性下降，导致NO和活性氧升高，影响细胞内的花生四烯酸代谢。我们研究了中枢神经系统特异性出现的金属硫蛋白3（MT-3）的金属结合能力。通过直观观察神经传递的方法，阐明了三丁基锡对神经传递的影响。结果表明，三丁基锡阻断了与学习记忆有关的长时程增强，并进一步将金属结合蛋白引入中枢神经系统，研究了活性氧自由基的障碍爆发机制。

In the present study, we intended to clarify a metabolism of trace metals, which affected central nervous system activity. With various cultured cells, we examined changes of a metallochaperone of copper, CCS, Cu,Zn-SOD, which received copper from CCS, and Ctr1, which was copper transporter in a copper lack and too much states. In a copper lack state, the quantity of protein of CCS and Cu,Zn-SOD increased. On the other hand, in a state having too much copper, the quantity of protein of CCS and Cu,Zn-SOD showed a significant fall. Furthermore, I made an animal having too much a zinc intake. In a state having too much zinc, a copper absorption obstruction in an intestinal tract was occurred. It was suggested that the copper in intestinal tract cell decreased, and a copper transporter protein ATP7A decreased as well.When it added copper chelate in a cultured cell of a nerve cell origin, it became clear that arachidonic acid metabolism changed in a cell. A fall of Cu,Zn-SOD activity by copper lack caused rises of NO and active oxygen species as the cause and affected arachidonic acid metabolism in a cell.We examined metal binding ability of metallothionein-3 (MT-3), which specifically emerged to a central nervous system. It became clear that copper-binding affinity of MT-3 is very much higher in comparison with other metallothioneins.With a visual observation method of neurotransmission, we clarified influence of tributyltin on the neurotransmission. As a result, tributyltin obstructed the long-term potentiation, which was related to learning and memory.Furthermore, I put the metal-binding protein, which caused the central nervous disorder and examination of obstacle outbreak mechanism of active oxygen species.