title: Effect of ferriprotoporphyrin IX and non-heme iron on the Ca(2+) pump of intact human red cells.
abstract: Previous studies have shown that ferriprotoporphyrin IX (FP) and non-heme iron have a marked inhibitory effect on the Ca(2+)-Mg(2+)-ATPase activity of isolated red cell membranes, the biochemical counterpart of the plasma membrane Ca(2+) 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 Ca(2+) homeostasis of abnormal cells. Active Ca(2+) extrusion by the plasma membrane Ca(2+) pump was measured in intact red cells that had been briefly preloaded with Ca(2+) 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 ( approximately 20%) of pump-mediated Ca(2+) extrusion and that non-heme iron induced a slight stimulation of the Ca(2+) efflux (11-20%), in contrast to the marked inhibitory effects on the Ca(2+)-Mg(2+)-ATPase of isolated membranes. Thus, FP and non-heme iron are unlikely to play a significant role in the altered Ca(2+) homeostasis of abnormal red cells.
authors.affiliation: Physiological Laboratory, University of Cambridge, Downing Street, Cambridge CB2 3EG, United Kingdom.
authors.forename: T
authors.initials: T
authors.lastname: Tiffert
authors.forename: V L
authors.initials: VL
authors.lastname: Lew
authors.forename: D
authors.initials: D
authors.lastname: Perdomo
authors.forename: H
authors.initials: H
authors.lastname: Ginsburg
mesh_terms: D001692:Biological Transport; D017301:Ca(2+) Mg(2+)-ATPase / Q000378:metabolism*; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D048429:Cell Size; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004910:Erythrocyte Membrane / Q000187:drug effects* / Q000201:enzymology; D006427:Hemin / Q000494:pharmacology*; D006461:Hemolysis; D006801:Humans; D007501:Iron / Q000494:pharmacology*; D007700:Kinetics; D009997:Osmotic Pressure
chemical_list: D004791:Enzyme Inhibitors; D000001:Calcimycin; D006427:Hemin; D007501:Iron; D017301:Ca(2+) Mg(2+)-ATPase; D002118:Calcium