Transport mechanisms for iron and other transition metals in rat and rabbit erythroid cells

Abstract

Earlier studies have shown that Fe2+ transport into erythroid cells is inhibited by several transition metals (Mn2+, Zn2+, Co2+, Ni2+) and that Fe2+ transport can occur by two saturable mechanisms, one of high affinity and the other of low affinity. Also, the transport of Zn2+ and Cd2+ into erythroid cells is stimulated by NaHCO3 and NaSCN. The aim of the present investigation was to determine whether all of these transition metals can be transported by the processes described for Fe2+, Zn2+ and Cd2+ and to determine the properties of the transport processes. Rabbit reticulocytes and mature erythrocytes and reticulocytes from homozygous and heterozygous Belgrade rats were incubated with radiolabelled samples of the metals under conditions known to be optimal for high‐ and low‐affinity Fe2+ transport and for the processes mediated by NaHCO3 and NaSCN. All of the metals were transported by the high‐ and low‐affinity Fe2+ transport processes and could compete with each other for transport. The Km and Vmax values and the effects of incubation temperature and metabolic inhibitors were similar for all the metals. NaHCO3 and NaSCN increased the uptake of Zn2+ and Cd2+ but not the other metals. The uptake of all of the metals by the high‐affinity process was much lower in reticulocytes from homozygous Belgrade rats than in those from heterozygous animals, but there was no difference with respect to low‐affinity transport. It is concluded that the high‐ and low‐affinity ‘iron’ transport mechanisms can also transport several other transition metals and should therefore be considered as general transition metal carriers.

Metal ion transporters in mammals: structure, function and pathological implications

“…In addition, mkÏmk mice also suffer from skin lesions reminiscent of defective zinc uptake. b rats are also reported to have widespread abnormalities in manganese metabolism, including impaired duodenal and reticulocyte uptake (Chua & Morgan, 1997;Savigni & Morgan, 1998). Thus, consistent with the substrate range which we determined for DCT1, the metabolism of a variety of metal A. Rolfs and M. A. Hediger J. Physiol.…”

Functional Expression of the Human hZIP2 Zinc Transporter

“…One explanation for this effect is that as pH increases, the concentration of HCO 3 Ϫ , which is present in the assay solution because of equilibration with atmospheric CO 2 , also increases. HCO 3 Ϫ treatment is known to stimulate zinc uptake activity in cultured fibroblasts and erythrocytes (6,22,23). Therefore, we examined the effects of HCO 3 Ϫ on the endogenous and hZip2 activities.…”

Characterization of the iron transporter DMT1 (NRAMP2/DCT1) in red blood cells of normal and anemic mk/mkmice

“…Importantly, the rates of 59 Fe transfer from 59 Fe-Tf to DP or SIH were not decreased in mk/mk reticulocytes, suggesting that in mk/mk reticulocytes the endosomal Fe metabolism (Fe release from Tf and its reduction by a putative Fe ϩϩϩ reductase) are functionally normal. These results indicate that the basic defect in mk/mk reticulocytes, as in those from b rats, 22,[25][26][27] resides in an impaired Fe ϩϩ transport efficiency across the endosomal membrane.…”

“…23,24 The metal is then transported through the endosomal membrane via a Fe ϩϩ transporter, a step found to be impaired in b reticulocytes. 22,[25][26][27] In different cell lines, including murine erythroleukemia (MEL) cells, as well as in Chinese hamster ovary (CHO), HEK293, and RAW cells expressing a transfected DMT1 complementary DNA (cDNA), the protein is detected primarily in Tf-positive compartments, a colocalization that supports a role for DMT1 in Tf-derived iron uptake within acidified endosomes. 9,28 Therefore, a large body of experimental data support the proposal that, in addition to its demonstrated role in iron acquisition at the intestinal brush border, DMT1 also transports iron across the membrane of acidified endosomes into the cytoplasm.…”