The human ZIP1 transporter mediates zinc uptake in human K562 erythroleukemia cells
The human ZIP1 transporter mediates zinc uptake in human K562 erythroleukemia cells
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DOI：
10.1074/jbc.m101772200
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发表时间：
2001-06-22
影响因子：
4.8
通讯作者：
Eide, DJ
中科院分区：
文献类型：
--
作者：
Gaither, LA;Eide, DJ
ZIP转运蛋白超家族在多种生物体的金属离子吸收中起着重要作用。在人类中有12个ZIP编码基因，我们假设这些蛋白质中的许多是锌转运蛋白。在这项研究中，我们解决了一个人类ZIP基因，hZIP 1，在锌转运的作用。首先，我们检查了过表达hZIP 1的K562红白血病细胞中的Zn-65摄取活性。这些细胞积累更多的锌比对照细胞，因为增加锌流入。此外，与其在锌吸收中的作用一致，hZIP 1蛋白定位于质膜。我们的研究结果还表明，hZIP 1是负责内源性锌摄取活性在K562细胞中，hZIP 1在未转染的K562细胞中表达，和mRNA水平的增加发现在hZIP 1过表达的细胞与增加的锌摄取活性。此外，hZIP 1依赖的Zn-65的摄取是生物化学上无法区分的内源性活性。最后，用反义寡核苷酸抑制内源性hZIP 1表达导致内源性Zn-65摄取活性显著降低。hZIP 1是K562细胞中主要的锌转运蛋白，加上它在许多正常细胞类型中的表达，这一观察表明hZIP 1在人体组织的锌摄取中起重要作用。
The ZIP superfamily of transporters plays important roles in metal ion uptake in diverse organisms. There are 12 ZIP-encoding genes in humans, and we hypothesize that many of these proteins are zinc transporters. In this study, we addressed the role of one human ZIP gene, hZIP1, in zinc transport. First, we examined Zn-65 uptake activity in K562 erythroleukemia cells overexpressing hZIP1. These cells accumulated more zinc than control cells because of increased zinc influx. Moreover, consistent with its role in zinc uptake, hZIP1 protein was localized to the plasma membrane. Our results also demonstrated that hZIP1 is responsible for the endogenous zinc uptake activity in K562 cells, hZIP1 is expressed in untransfected K562 cells, and the increase in mRNA levels found in hZIP1-overexpressing cells correlated with the increased zinc uptake activity. Furthermore, hZIP1-dependent Zn-65 uptake was biochemically indistinguishable from the endogenous activity. Finally, inhibition of endogenous hZIP1 expression with antisense oligonucleotides caused a marked decrease in endogenous Zn-65 uptake activity. The observation that hZIP1 is the major zinc transporter in K562 cells, coupled with its expression in many normal cell types, indicates that hZIP1 plays an important role in zinc uptake in human tissues.