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 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 lift: 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 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 of those applied to the isolated red cell membrane preparations. The results showed that FP caused a marginal inhibition (similar to 20%) of pump-mediated Ca2+ extrusion and that nonheme 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, EP and non-he me iron are unlikely to play a significant role in the altered Ca2+ homeostasis of abnormal red cells.