Kohno H, Taketani S, Tokunaga R
Department of Hygiene, Kansai Medical University, Osaka, Japan.
Biometals. 1993 Summer;6(2):77-83. doi: 10.1007/BF00140107.
The effect of lead on cellular iron metabolism has been investigated using human erythroleukemia (K562) cells. When the cells were cultured with 100 microM Pb2+ for 48 h, the rate of cellular iron uptake from transferrin decreased to 46% of that in untreated cells. Scatchard analysis of the binding data revealed that this reduction was the result of a decrease in the number of transferrin receptors rather than an alteration in ligand-receptor affinity. The results of immunoprecipitation 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, as determined by immunoblotting. Moreover, the biosynthesis of the receptor was unaffected by lead treatment. Thus, the down-regulation of surface transferrin receptors in lead-treated cells might be due to a redistribution of receptors rather than an actual loss of receptors from the cell. Using kinetic analysis, it was shown that redistribution of the receptor did not result from the alteration in the rates of transferrin receptor recycling. A comparison of the amounts of transferrin receptor on the cell surface and in the cycling pool revealed that the sequestration of the receptor from normal flow through the cycle might cause down-regulation of the surface receptor.
利用人红白血病（K562）细胞研究了铅对细胞铁代谢的影响。当细胞用100微摩尔/升的Pb2+培养48小时后，细胞从转铁蛋白摄取铁的速率降至未处理细胞的46%。对结合数据进行Scatchard分析表明，这种降低是转铁蛋白受体数量减少的结果，而非配体-受体亲和力的改变。对细胞表面转铁蛋白受体进行免疫沉淀的结果也证实，经铅处理的细胞中转铁蛋白受体的表达降低。如免疫印迹法所测定，用铅处理导致转铁蛋白受体下调并非是由于受体总量减少。此外，受体的生物合成不受铅处理的影响。因此，经铅处理的细胞表面转铁蛋白受体下调可能是由于受体的重新分布，而非细胞实际丢失了受体。通过动力学分析表明，受体的重新分布并非是由于转铁蛋白受体循环速率的改变所致。对细胞表面和循环池中转铁蛋白受体的量进行比较发现，受体从正常的循环流动中被隔离可能导致表面受体下调。
