Inhibition of cellular iron uptake by haem in mouse erythroleukaemia cells

Haemin inhibited iron uptake from transferrin (Tf) by mouse erythroleukaemia cells (MELC) induced for differentiation by hexamethylene bisacetamide (HMBA). The rate of 59Fe internalization was decreased, but the rate and the extent of 125I-Tf endocytosis was unaffected by the addition of haemin. Haemin inhibited 59Fe incorporation into haem by a greater proportion than the overall uptake of 59Fe from Tf. The reduction of total cellular 59Fe uptake was more pronounced at 59Fe-Tf concentrations closer to saturation. Exogenous 5-aminolaevulinic acid stimulated 59Fe utilization for haem synthesis in MELC but did not revert the inhibition induced by haemin. Haem synthesis measured by 14C-glycine incorporation into haem was maintained for at least 1 h without an external transferrin iron source and was inhibited by the addition of haemin equally over the whole range of Tf concentrations studied. Desferrioxamine (DFO) stimulated cellular uptake of 59Fe by the uninduced cells and reverted the inhibition of 59Fe transport into HMBA treated cells caused by haemin. Addition of DFO within a short-term incubation had no effect on haem synthesis measured by 14C-glycine incorporation into haem. No evidence for a direct effect of haem on the transferrin cycle or iron release was found. It was concluded that the reduction of iron uptake by haemin treated MELC is secondary to the decrease in iron utilization for haem synthesis.