| Project/Area Number |
11470093
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Hygiene
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| Research Institution | Tohoku University |
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Principal Investigator |
NAKAI Kunihiko Tohoku University, Graduate School of Medicine, Department of Environmental Health Sciences, Associate Professor, 大学院・医学系研究科, 助教授 (00291336)
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| Co-Investigator(Kenkyū-buntansha) |
KAMEO Satomi Tohoku University, Graduate School of Medicine, Department of Environmental Health Sciences, Research Associate, 大学院・医学系研究科, 助手 (40312558)
NAGANUMA Akira Tohoku University, Graduate School of Science, Laboratory of Molecular and Biochemical Toxicology, Professor, 大学院・薬学研究科, 教授 (80155952)
SATOH Hiroshi Tohoku University, Graduate School of Medicine, Department of Environmental Health Sciences, Professor, 大学院・医学系研究科, 教授 (40125571)
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| Project Period (FY) |
1999 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥13,800,000 (Direct Cost: ¥13,800,000)
Fiscal Year 2001: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 2000: ¥3,900,000 (Direct Cost: ¥3,900,000)
Fiscal Year 1999: ¥7,900,000 (Direct Cost: ¥7,900,000)
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| Keywords | Nitric Oxides / S-nitrosylation / Metal-binding proteins / Metal metabolism / Glutamate / Metallothionein / Methylmercury / Endotoxin / S-ニシロソ化 / メタラチオネイン / s-ニトロソ化 / ノックアウトマウス |
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| Research Abstract |
The influence of nitric oxides and its s-nitrosylated metabolites on the metabolism of metal and essential elements had been examined in mice. In the first experiment, the mice were treated with endotoxin (100-1000 ug/kg, i.p.) and then the NOx and metal concentrations in the perfusate of the hippocampus C3A region obtained with the microdialisys were determined using HPLC (for Nox) and ICP-MS (for zinc and cupper). The results showed that the treatment with endotoxin significanytly increased in the concentrations of both NOx and zinc in the perfusates. These results suggest that the overproduction of NO in the brain might mobilized the intracellular zinc. In the second experiment, the mice were exposed prenataly to methylmercury to make the animal model to examine the functional roles of nitric oxides in the neurodevelopment. Methylmercury is known to induce the NO synthase. The association of the neu robehavioral changes with the metabolism of glutamate in the hippocampus CA3 region was examined. Although the treatment with methylmercury did not increase the extracellular glutamate concentration, the mobilization of glutamate was significantly inhibited. There were also some data showing the disturbance in the concentrations of some metal components in the brain after the methylmercury treatment. However, no direct evidence indicating the positive association between methylmercury-induced NO production and the alternation of metal metabolism. Further studies regarding the biological relationship between NO generation and the metal mobilization is required to understand the biological roles of metals and the metal-binding proteins.
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