Regulation Mechanisms of Metabolism of Essential Elements by Metal-Interactions

我们研究了一种新的铁结合蛋白的性质，以前从大鼠肝脏中纯化。用胰蛋白酶消化蛋白质并分析肽。胰蛋白酶肽的部分氨基酸序列与大鼠核糖体蛋白P2的氨基酸序列一致。在与铁-转铁蛋白孵育的细胞中，约1.5%的放射性铁<59>在与抗铁结合蛋白血清的免疫沉淀物中被发现。暴露于砷或镉离子的Hela细胞引起血红素加氧酶的合成显着增加，亚硒酸钠的存在抑制诱导。这些结果表明，硒拮抗重金属离子对血红素加氧酶的诱导。用去铁胺处理细胞导致核糖核苷酸还原酶活性、DNA合成和细胞生长减少。将细胞暴露于抗转铁蛋白受体抗体42/6（其阻断铁补充剂进入细胞）引起核糖核苷酸还原酶活性和DNA合成的降低。当红白血病（K562）细胞与Pb^&lt;2+&gt;共同培养时，细胞从转铁蛋白中摄取铁的速率下降到未处理细胞的46%。这种减少是细胞表面上的转铁蛋白受体的数量减少的结果，也证实了铅处理的细胞的转铁蛋白受体的表达减少。通过铅处理的转铁蛋白受体的下调并不是由于受体总量的减少。

We examined the properties of a new iron-binding protein purified previously from rat liver. The protein was digested with trypsin and the peptides were analyzed. The partial amino acid sequences of the tryptic peptides coincided with that of rat ribosomal protein P2. About 1.5% of radioactive iron in cells incubated with ^<59>Fe-transferrin was found in immunoprecipitates with anti-iron-binding protein serum. Exposure of Hela cells to arsenite or cadmium ions caused a marked increase in the synthesis of heme oxygenase, and the presence of sodium selenite suppressed the induction. These results indicated that selenium antagonizes the induction of heme oxygenase by heavy metals ions. Treatment of the cells with desferrioxamine resulted in decreases of ribonucleotide reductase activity, DNA synthesis, and cell growth. Exposure of the cells to anti-transferrin receptor antibody, 42/6, which blocks iron supplement into cells caused decreases of ribonucleotide reductase activity and DNA synthesis. When erythroleukemia (K562) cells were cultured with Pb^<2+>, the rate of cellular iron uptake from transferrin decreased to 46% of that in untreated cells. This reduction was the result of a decrease in the number of transferrin receptors on the cell surface also confirmed the decreased expression of transferrin receptors by lead-treated cells. The down-regulation of transferrin receptors by treatment with lead did not result from a decrease in the total amount of the receptor.