Jordan I, Kaplan J
Department of Pathology, University of Utah College of Medicine, Salt Lake City 84102.
Biochem J. 1994 Sep 15;302 ( Pt 3)(Pt 3):875-9. doi: 10.1042/bj3020875.
Mammalian cells accumulate iron from ferric citrate or ferric nitrilotriacetate through the activity of a transferrin-independent iron transport system [Sturrock, Alexander, Lamb, Craven and Kaplan (1990) J. Biol. Chem. 265, 3139-3145]. The uptake system might recognize and transport ferric-anion complexes, or cells may reduce ferric iron at the surface and then transport ferrous iron. To distinguish between these possibilities we exposed cells to either [59Fe]ferric citrate or ferric [14C]citrate and determined whether accumulation of iron was accompanied by the obligatory accumulation of citrate. In HeLa cells and human skin fibroblasts the rate of accumulation of iron was three to five times greater than that of citrate. Incubation of fibroblasts with ferric citrate or ferric ammonium citrate resulted in an enhanced accumulation of iron and citrate; the molar ratio of accumulation approaching unity. A similar rate of citrate accumulation, however, was observed when ferric citrate-incubated cells were exposed to [14C]citrate alone. Further studies demonstrated the independence of iron and citrate accumulation: addition of unlabelled citrate to cells decreased the uptake of labelled citrate without affecting the accumulation of 59Fe; iron uptake was decreased by the addition of ferrous chelators whereas the uptake of citrate was unaffected; reduction of ferric iron by ascorbate increased the uptake of iron but had no effect on the uptake of citrate. When HeLa cells were depleted of calcium, iron uptake decreased, but there was little effect on citrate uptake. These results indicate that transport of iron does not require the obligatory transport of citrate and vice versa. The mammalian transferrin-independent iron transport system appears functionally similar to iron transport systems in both the bacterial and plant kingdoms which require the activities of both a surface reductase and a ferrous metal transporter.
哺乳动物细胞通过一种不依赖转铁蛋白的铁转运系统的活性，从柠檬酸铁或次氮基三乙酸铁中积累铁元素[斯特罗克、亚历山大、兰姆、克雷文和卡普兰（1990年）《生物化学杂志》265卷，3139 - 3145页]。摄取系统可能识别并转运铁阴离子复合物，或者细胞可能在表面将三价铁还原，然后转运二价铁。为了区分这些可能性，我们将细胞暴露于[59Fe]柠檬酸铁或[14C]柠檬酸铁中，并确定铁的积累是否伴随着柠檬酸的必然积累。在HeLa细胞和人皮肤成纤维细胞中，铁的积累速率比柠檬酸的积累速率大三到五倍。用柠檬酸铁或柠檬酸铁铵培养成纤维细胞，会导致铁和柠檬酸的积累增加；积累的摩尔比接近1。然而，当用柠檬酸铁培养的细胞单独暴露于[14C]柠檬酸时，观察到类似的柠檬酸积累速率。进一步的研究证明了铁和柠檬酸积累的独立性：向细胞中添加未标记的柠檬酸会降低标记柠檬酸的摄取，而不影响59Fe的积累；添加二价铁螯合剂会降低铁的摄取，而柠檬酸的摄取不受影响；抗坏血酸将三价铁还原会增加铁的摄取，但对柠檬酸的摄取没有影响。当HeLa细胞缺钙时，铁的摄取减少，但对柠檬酸的摄取影响很小。这些结果表明，铁的转运不需要柠檬酸的必然转运，反之亦然。哺乳动物不依赖转铁蛋白的铁转运系统在功能上似乎类似于细菌和植物界的铁转运系统，后者需要表面还原酶和二价金属转运蛋白的共同作用。
