Synergistic accumulation of iron and zinc by cultured astrocytes

Iron and zinc are essential for normal brain function, yet the mechanisms used by astrocytes to scavenge non-transferrin-bound iron (NTBI) and zinc are not well understood. Ischaemic stroke, traumatic brain injury and Alzheimer's disease are associated with perturbations in the metabolism of NTBI and zinc, suggesting that these two metals may collectively contribute to pathology. The present study has investigated the accumulation of NTBI and zinc by rat primary astrocyte cultures. It was found that astrocytes express mRNA for both divalent metal transporter 1 (DMT1) and Zip14, indicating the potential for these transporters to contribute to the accumulation of NTBI and zinc by these cells. Astrocytes were found to accumulate iron from ferric chloride in a time- and dose-dependent manner, and the rate of accumulation was strongly stimulated by co-incubation with zinc acetate. In addition, cultured astrocytes rapidly accumulated zinc from zinc acetate, and this accumulation was stimulated by co-incubation with ferric chloride. Because a synergistic stimulation of iron and zinc accumulation is inconsistent with the known properties of DMT1 and Zip14, the present results suggest that additional mechanisms assist astrocytes to scavenge iron and zinc when they are present together in the extracellular compartment. These mechanisms may be involved in disorders that involve elevations in the extracellular concentrations of these metal ions.