Regulation Mechanisms of Metabolism of Essential Elements by Metal-Interactions

我们研究了先前从大鼠肝脏中纯化的一种新的铁结合蛋白的性质。用胰酶消化蛋白，并对其多肽进行分析。其部分氨基酸序列与大鼠核糖体蛋白P2的氨基酸序列一致。在与转铁蛋白共同孵育的细胞中，约有1.5%的放射性铁存在于含抗铁结合蛋白血清的免疫沉淀物中。亚砷酸盐或镉离子可引起Hela细胞血红素加氧酶的合成显著增加，而亚硒酸钠的存在则抑制这种诱导作用。这些结果表明，硒对重金属离子诱导的血红素加氧酶有拮抗作用。用去铁胺处理细胞后，核糖核苷酸还原酶活性、DNA合成和细胞生长均下降。将细胞暴露在抗转铁蛋白受体抗体42/6中，阻断细胞内的铁补充，导致核糖核苷酸还原酶活性和DNA合成减少。红白血病(K562)细胞与Pb2+、Gt+共同培养后，细胞铁摄取率下降至未处理细胞的46%。这种减少是细胞表面转铁蛋白受体数量减少的结果，也证实了铅处理细胞转铁蛋白受体表达的减少。用铅处理后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.