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

本文研究了一氧化氮及其S亚硝酸盐代谢产物对小鼠体内金属元素和必需元素代谢的影响。在第一个实验中，给小鼠注射内毒素(100-1000微克/公斤，ip)。用高效液相色谱(NOx)和电感耦合等离子体质谱(ICPMS)分别测定用微量分析仪测得的海马区C3A区灌流液中NOx和金属的浓度。结果表明，经内毒素处理后，灌流液中NOx和锌的浓度均显著升高。这些结果表明，脑内NO的过量产生可能动员了细胞内的锌。在第二个实验中，将小鼠产前暴露于甲基汞，以制作动物模型，以考察一氧化氮在神经发育中的功能作用。已知甲基汞可诱导一氧化氮合酶。观察海马CA3区神经行为改变与谷氨酸代谢的关系。甲基汞处理虽然没有提高胞外谷氨酸浓度，但对谷氨酸的动员有明显的抑制作用。还有一些数据显示，甲基汞处理后，大脑中一些金属成分的浓度发生了变化。然而，没有直接证据表明甲基汞诱导的NO产生与金属代谢的变化呈正相关。为了了解金属和金属结合蛋白的生物学作用，需要进一步研究NO产生和金属动员之间的生物学关系。

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.