Effect of ferriprotoporphyrin IX and non-heme iron on the Ca²⁺ pump of intact human red cells

Previous studies have shown that ferriprotoporphyrin IX (FP) and non- heme iron have a marked inhibitory effect on the Ca²⁺-Mg²⁺-ATPase activity of isolated red cell membranes, the biochemical counterpart of the plasma membrane Ca²⁺ pump (PMCA). High levels of membrane-bound FP and non- heme iron have been found in abnormal red cells such as sickle cells and malaria-infected red cells, associated with a reduced life span. It was important to establish whether sublytic concentrations of FP and non-heme iron would also inhibit the PMCA in normal red cells, to assess the possible role of these agents in the altered Ca²⁺ homeostasis of abnormal cells. Active Ca²⁺ extrusion by the plasma membrane Ca²⁺ pump was measured in intact red cells that had been briefly preloaded with Ca²⁺ by means of the ionophore A23187. The FP and non-heme iron concentrations used in this study were within the range of those applied to the isolated red cell membrane preparations. The results showed that FP caused a marginal inhibition (~20%) of pump-mediated Ca²⁺ extrusion and that non-heme iron induced a slight stimulation of the Ca²⁺ efflux (11-20%), in contrast to the marked inhibitory effects on the Ca²⁺-Mg²⁺-ATPase of isolated membranes. Thus, FP and non-heme iron are unlikely to play a significant role in the altered Ca²⁺ homeostasis of abnormal red cells.