Iron Transport through Ferroportin Is Induced by Intracellular Ascorbate and Involves IRP2 and HIF2 alpha

Journal article, 2014

A few tightly regulated transport proteins mediate iron absorption across the intestinal epithelium. At the basolateral border of intestinal cells there is one identified transporter, ferroportin, for the transfer of intracellular iron to the vascular system. Here, we investigate the effects of ascorbate (vitamin C) on the regulation of ferroportin in human intestinal Caco-2 cells using ELISA and Western Blot analyses. The results indicate that ferroportin protein levels peak at 100 mu M of added ascorbate with an increase of 274% (p = 0.02). At 150 mu M of ascorbate, the increase was only 28% (p = 0.04), and at 200 mu M there was no significant change from the baseline control. In addition, the ascorbate-induced, (at 150 mu M) up-regulated ferroportin levels were associated with increased Fe-55 transport across the basolateral border (19%, p = 0.03). Ascorbate-induced up-regulation of cellular ferroportin levels (no added iron) was associated with increased levels of the iron regulatory protein IRP2 (230%, p = 0.0009), and the hypoxia-inducible factor HIF2 alpha (69%, p = 0.03). Thus, iron transport across the basal border via ferroportin is influenced by the intracellular status of ascorbate and IRP2 and HIF2 alpha are involved. We discuss possible reasons for the ascorbate-effects and the dependence of cellular growth conditions for iron transport-related protein expression.