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-hems i ron have a marked inhibitory effect on the Ca2+-Mg2+-ATPase activity of iso lated red cell membranes, the biochemical counterpart of the plasma membran e 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 lift: span. It was important to estab lish whether sublytic concentrations of FP and non-heme iron would also inh ibit the PMCA in normal red cells, to assess the possible role of these age nts in the altered Ca2+ homeostasis of abnormal cells. Active Ca2+ extrusio n by the plasma membrane Ca2+ pump was measured in intact red cells that ha d bren briefly preloaded with Ca2+ by means of the ionophore A23187. The FP and nonheme iron concentrations used in this study were within the range o f those applied to the isolated red cell membrane preparations. The results showed that FP caused a marginal inhibition (similar to 20%) of pump-media ted Ca2+ extrusion and that nonheme iron induced a slight stimulation of th e Ca2+ efflux (11-20%), in contrast to the marked inhibitory effects on the Ca2+-Mg2+-ATPase of isolated membranes. Thus, EP and non-he me iron are un likely to play a significant role in the altered Ca2+ homeostasis of abnorm al red cells.