INFLUENCE ON IMMUNOREACTIVE FOLATE-BINDING PROTEINS OF EXTRACELLULAR FOLATE CONCENTRATION IN CULTURED HUMAN-CELLS
INFLUENCE ON IMMUNOREACTIVE FOLATE-BINDING PROTEINS OF EXTRACELLULAR FOLATE CONCENTRATION IN CULTURED HUMAN-CELLS
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DOI：
10.1172/jci113469
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发表时间：
1988-05-01
影响因子：
15.9
通讯作者：
KOLHOUSE, JF
中科院分区：
文献类型：
--
作者：
KANE, MA;ELWOOD, PC;KOLHOUSE, JF
在培养的人鼻咽癌（KB）细胞中直接研究了细胞外叶酸浓度对叶酸转运蛋白及其可溶性产物细胞水平的影响。通过放射免疫测定，叶酸运输组分和可溶性叶酸结合蛋白的水平为58。17（平均+-）SD)和5 .+-。在标准培养基（含2,300 mM叶酸）中维持的KB细胞中，分别为2 pmol/mg细胞蛋白。这些水平显著增加到182 +-。34和26，+-在低叶酸培养基（含2-10 mM 5-甲基四氢叶酸）中连续传代的KB细胞中，分别为6 pmol/mg细胞蛋白。在含有< 2 nM叶酸的极低叶酸培养基中连续传代的KB细胞中，叶酸结合蛋白水平的增加更快，并且通过添加100 mM 5-甲基四氢叶酸或0.1-1 .mu来阻止。M - 5-甲酰基四氢叶酸。当将在低叶酸培养基中传代的KB细胞传代回标准培养基或添加了还原叶酸的低叶酸培养基时，两种叶酸结合蛋白的水平都向在标准培养基中持续保持的KB细胞水平线性填充。叶酸转运蛋白在人和小鼠乳腺肿瘤细胞中发现并发生了类似的变化。这些研究表明，叶酸转运系统可能通过细胞内代谢物水平的变化受到细胞外叶酸浓度的调节。
The influence of extracellular folate concentration on cellular levels of the folate transport protein and its soluble product was studied directly in cultured human nasopharyngeal carcinoma (KB) cells. As determined by radioimmunoassay, levels of the folate transport portien and the soluble folate-binding protein were 58 .+-. 17 (mean .+-. SD) and 5 .+-. 2 pmol/mg cell protein, respectively, in KB cells maintained in standard medium (containing 2,300 mM folic acid). These levels significantly increased to 182 .+-. 34 and 26 .+-. 6 pmol/mg cell protein, respectively, in KB cells serially passaged in low folate medium (containing 2-10 mM 5-methyltetrahydrofolate). Increases in folate-binding protein levels occurred more rapidly in KB cells serially passaged in very low folate medium containing < 2 nM folate and were prevented by the addition of 100 mM 5-methyltetrahydrofolate or 0.1-1 .mu.M 5-formyltetrahydrofolate to this medium. When KB cells which had been passaged in low folate medium were passaged back into either standard medium or low folate medium supplemented with reduced folates, the levels of both folate-binding proteins fill linearly towards the levels in KB cells continuously maintained in standard medium. The folate transport protein was identified in and underwent similar changes in human and mouse mammary tumor cells. These studies indicate that the folate transport system is probably regulated by the extracellular folate concentration through changes in intracellular metabolite levels.