Regulation of the erythroid zinc transporters Zip10, Zip8 and ZnT1 during zinc deficiency

Abstract

Red blood cell (RBC) zinc uptake can be regulated in a zinc-responsive and a bicarbonate-dependent manner. However, the zinc transporters involved in zinc trafficking of RBCs have not been clarified yet. Previously, we showed ZnT1 expression in differentiating erythroid progenitors. In our current studies, the presence of Zip8 and Zip10 was detected in these cells. Consequently, the temporal expression pattern of these transporters was evaluated during the terminal differentiation of murine erythroid progenitor cells following EPO-induction. Upregulation of Zip8 and Zip10 was observed at the early time-points of EPO-induction while the EPO-dependent expression of ZnT1 was detectable only at the later stage. To determine whether these transporters contribute to the higher RBC 65Zn uptake in zinc deficient conditions, a controlled dietary zinc intake study was conducted with mice. Higher 65Zn accumulation in vitro, and a prominent increase of Zip10 protein levels in RBCs were observed during deficiency, whereas only a slight decrease in ZnT1 was detected. However, Zip8 did not show any responsiveness to zinc status. These results support the involvement of Zip10 and ZnT1 as the transporters mediating changes in zinc metabolism in RBCs. On the other hand, Zip8 may facilitate the constitutive bicarbonate-mediated zinc uptake in a zinc status-independent manner. Supported by NIH Grant DK 31127 (RJC) and CALS Alumni Fellowship (MSR).