Human ZIP1 is a major zinc uptake transporter for the accumulation of zinc in prostate cells

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 Vmax for zinc uptake was increased with no change in Km. Along with the increased intracellular accumulation of zinc, the overexpression of hZIP1 also results in the inhibition of growth of PC-3 cells. Down-regulation of hZIP1 by treatment of PC-3 cells with hZIP1 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.