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Effects of the s-nitrosylation of metal-binding proteins bu nitric oxides on the metabolism of metals

一氧化氮金属结合蛋白的s-亚硝基化对金属代谢的影响

基本信息

批准号：
11470093
负责人：
NAKAI Kunihiko
金额：
$ 8.83万
依托单位：
Tohoku University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2001
项目状态：
已结题

项目摘要

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.

本文研究了一氧化氮及其s-亚硝基化代谢产物对小鼠体内金属和必需元素代谢的影响。在第一个实验中，用内毒素（100-1000 ug/kg，i. p.）然后使用HPLC（对于NOx）和ICP-MS（对于锌和铜）测定用微量透析法获得的海马C3 A区灌流液中的NOx和金属浓度。结果表明，内毒素处理后，灌流液中氮氧化物和锌的浓度均显著增加。提示脑组织中NO的过量产生可能是对细胞内锌的动员。第二个实验采用小鼠出生前暴露于甲基汞的方法建立动物模型，研究一氧化氮在神经发育中的作用。已知甲基汞可诱导NO合酶。观察神经行为学改变与海马CA 3区谷氨酸代谢的关系。虽然甲基汞处理并没有增加细胞外谷氨酸浓度，但谷氨酸的动员被显著抑制。还有一些数据显示，在甲基汞处理后，大脑中某些金属成分的浓度出现了紊乱。然而，没有直接证据表明甲基汞诱导的NO产生与金属代谢的改变之间的正相关。需要进一步研究NO生成和金属动员之间的生物学关系，以了解金属和金属结合蛋白的生物学作用。