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

研究了一氧化氮及其s-亚硝基化代谢物对小鼠体内金属和必需元素代谢的影响。第一个实验用内毒素（100 ~ 1000 ug/kg, i.p）处理小鼠，用HPLC（测定NOx）和ICP-MS（测定锌和铜）测定微透析所得海马C3A区灌注液中NOx和金属的浓度。结果表明，内毒素处理显著提高了灌注液中NOx和锌的浓度。这些结果提示，脑内一氧化氮的过量产生可能调动了细胞内锌。在第二个实验中，小鼠在出生前暴露于甲基汞中，以制作动物模型，以检查一氧化氮在神经发育中的功能作用。甲基汞可以诱导NO合成酶。研究了新行为改变与海马CA3区谷氨酸代谢的关系。虽然甲基汞处理没有增加细胞外谷氨酸浓度，但谷氨酸的动员明显受到抑制。还有一些数据显示，在甲基汞治疗后，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生成与金属代谢的变化之间存在正相关。为了进一步了解金属及其结合蛋白的生物学作用，需要进一步研究NO生成与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.