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Physiological roles of a new copper-binding protein : relationship between new copper-binding protein and hereditary copper

新型铜结合蛋白的生理作用：新型铜结合蛋白与遗传性铜之间的关系

基本信息

批准号：
03454199
负责人：
KOJIMA Yutaka
金额：
$ 3.14万
依托单位：
HOKKAIDO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1991
资助国家：
日本
起止时间：
1991 至 1992
项目状态：
已结题

项目摘要

Cu is an essential trace element which requires a delicate cellular balance between a necessary concentration and toxicity. Metallothionein (MT), a low molecular weight heavy-binding protein, plays an important role in Cu homeostasis and detoxification. In this study, the Cu-binding low molecular weight proteins induced by single or multiple Cu-injection rats were identified as Cu-MTs and/or a new Cu-binding protein using a new purification procedure of both of the new protein and Cu-MT under the aerobic condition.There were many debate on the existence of MT and other Cu-binding proteins which appeared in tissues of Cu-loaded animals. We settled the confusion by demonstrating of the presence of a new Cu-induced protein which did not belong to MT group, because the protein was a low cystein content and bound two Cu atoms per a molecule. We did show that only Cu-MT was induced by a single injection of Cu in rat liver and both of Cu-MT and the new protein appeared by the multiple injections of Cu. This result suggests that new protein was synthesized by excessive Cu which was not sufficiently detoxified by Cu-MT to serve detoxification of Cu when the hepatic Cu content increased and reached a certain threshold value.In addition, we established that excess amounts of Cu in the kidney of Macular mice, a model for Menke's disease (X-linked disorder of Cu metabolism), were found as Cu-MT. The Cu-MT was predominant in the proximal convoluted tubule cells of the cortex. MT mRNA was also observed in the cortex, indicating that the protein was biosynthesized in this region. On the other hand, the new Cu-binding protein was hardly detected in the kidney of macular mice. From these results the new protein was considered to play a key role in Cu-metabolism.

铜是一种必需的微量元素，需要在必要的浓度和毒性之间保持微妙的细胞平衡。金属硫蛋白（MT）是一种低分子量重结合蛋白，在铜稳态和解毒中发挥重要作用。在这项研究中，单次或多次注射铜的大鼠诱导的铜结合低分子量蛋白被鉴定为Cu-MT和/或新的铜结合蛋白，使用新蛋白和Cu-MT在有氧条件下的新纯化程序。对于MT和出现在铜负载动物组织中的其他铜结合蛋白的存在存在很多争论。我们通过证明一种新的铜诱导蛋白的存在来解决这个困惑，该蛋白不属于 MT 组，因为该蛋白半胱氨酸含量低，并且每个分子结合两个铜原子。我们确实表明，在大鼠肝脏中单次注射 Cu 仅诱导 Cu-MT，而多次注射 Cu 则同时出现 Cu-MT 和新蛋白。这一结果表明，当肝脏铜含量增加并达到一定阈值时，过量的铜合成了新的蛋白质，而铜-MT不能充分解毒以服务铜的解毒作用。此外，我们建立了黄斑小鼠肾脏中过量的铜，门克病（X连锁铜代谢障碍）模型，被发现为铜-MT。 Cu-MT 在皮质的近曲小管细胞中占主导地位。在皮质中也观察到了 MT mRNA，表明该蛋白质是在该区域生物合成的。另一方面，在黄斑小鼠的肾脏中几乎检测不到新的铜结合蛋白。从这些结果来看，新蛋白质被认为在铜代谢中发挥关键作用。