| Project/Area Number |
03454199
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Hygiene
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| Research Institution | HOKKAIDO UNIVERSITY |
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Principal Investigator |
KOJIMA Yutaka Hokkaido Univ., Grad. School of Env. Earth Sci., Prof., 大学院・地球環境科学研究科, 教授 (50135555)
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| Co-Investigator(Kenkyū-buntansha) |
KURASAKI Masaaki Hokkaido Univ., Grad. School of Env. Earth Sci., Inst., 大学院・地球環境科学研究科, 助手 (80161727)
NIIOKA Tadashi Hokkaido Univ., Grad. School of Env. Earth Sci., Assoc. Prof., 大学院・地球環境科学研究科, 助教授 (20123953)
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| Project Period (FY) |
1991 – 1992
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| Project Status |
Completed (Fiscal Year 1992)
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| Budget Amount *help |
¥4,900,000 (Direct Cost: ¥4,900,000)
Fiscal Year 1992: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1991: ¥4,200,000 (Direct Cost: ¥4,200,000)
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| Keywords | hereditary copper metabolism disorders / copper-induced low molecular weight protein / metallothionein / menkes disease / macular mouse / amino acid composition / liver / kidney / 遺伝性重金属代謝異常症 / ウィルソン病 / メンキース病 / ウィルソン病モデル動物 / LECラット / 銅のみと結合する蛋白質 / メンキ-ス病 |
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| Research Abstract |
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.
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