Human ZIP1 is a major zinc uptake transporter for the accumulation of zinc in prostate cells
Human ZIP1 is a major zinc uptake transporter for the accumulation of zinc in prostate cells
复制标题
DOI：
10.1016/s0162-0134(03)00249-6
复制
发表时间：
2003-08-01
影响因子：
3.9
通讯作者：
Costello, LC
中科院分区：
文献类型：
--
作者：
Franklin, RB;Ma, J;Costello, LC
人类和其他动物的前列腺积累的锌水平是其他组织中发现的锌水平的3-10倍。与这种积累锌的能力相关的是人类前列腺细胞中的快速锌摄取过程，我们先前将其鉴定为hZIP 1锌转运蛋白。我们现在提供了额外的证据，证明hZIP 1是一种重要的操作转运蛋白，允许锌的运输和积累。研究表明，hZIP 1（SLC 39 A1）而不是hZIP 2（SLC 39 A2）在锌积累的人前列腺细胞系LNCaP和PC-3中表达。过表达hZIP 1的转染PC-3细胞表现出增加的锌摄取和积累。锌吸收的Vmax增加，而K-m无变化。沿着细胞内锌积累的增加，hZIPI的过表达也导致PC-3细胞生长的抑制。通过用hZIPI反义寡核苷酸处理PC-3细胞下调hZIPI导致锌摄取减少。从锌螯合与柠檬酸盐的锌的摄取是从游离锌离子一样快，但是，细胞不采取锌螯合与EDTA。锌的细胞摄取不依赖于游离Zn 2+离子的可用池。相反，转运机制似乎涉及从低分子量配体转运锌，所述低分子量配体作为与锌的相对松散结合的络合物存在于循环中。(C)2003年爱思唯尔公司All rights reserved.
The prostate gland of humans and other animals accumulates a level of zinc that is 3-10 times greater than that found in other tissues. Associated with this ability to accumulate zinc is a rapid zinc uptake process in human prostate cells, which we previously identified as the hZIP1 zinc transporter. We now provide additional evidence that hZIP1 is an important operational transporter that allows for the transport and accumulation of zinc. The studies reveal that hZIP1 (SLC39A1) but not hZIP2 (SLC39A2) is expressed in the zinc-accumulating human prostate cell lines, LNCaP and PC-3. Transfected PC-3 cells that overexpress hZIP1 exhibit increased uptake and accumulation of zinc. The V-max for zinc uptake was increased with no change in K-m,. Along with the increased intracellular accumulation of zinc, the overexpression of hZIPI also results in the inhibition of growth of PC-3 cells. Down-regulation of hZIPI by treatment of PC-3 cells with hZIPI antisense oligonucleotide resulted in a decreased zinc uptake. Uptake of zinc from zinc chelated with citrate was as rapid as from free zinc ions; however, the cells did not take up zinc chelated with EDTA. The cellular uptake of zinc is not dependent upon an available pool of free Zn2+ ions. Instead, the mechanism of transport appears to involve the transport of zinc from low molecular weight ligands that exist in circulation as relatively loosely bound complexes with zinc. (C) 2003 Elsevier Inc. All rights reserved.