Chelator-mediated iron efflux from reticulocytes.
The mechanism by which bipyridine and phenanthroline types of iron chelator inhibit iron uptake from transferrin and iron efflux mediated by pyridoxal isonicotinoyl hydrazone was investigated using rabbit reticulocytes with the aim of providing more information on the normal process of iron uptake by developing erythroid cells. It was shown that the chelators block cellular uptake by chelating the iron immediately after release from transferrin while it is still in the membrane fraction of the cells. The iron-chelator is then released from the cells by a process which is very similar to that of transferrin release with respect to kinetics and sensitivity to incubation temperature and the effects of metabolic inhibitors and other chemical reagents. These results are compatible with the conclusion that both transferrin and the iron-chelators in the cells are mainly present in endocytotic vesicles and are released from the cells by exocytosis. The chelators were also shown to block the pyridoxal isonicotinoyl hydrazone-mediated efflux of iron from cells which had taken up iron in the presence of isoniazid, an inhibitor of haem synthesis, by chelating the iron in the cytosol and the mitochondria. In this case, the iron-chelator complexes were not released from the cells. Measurement of the diethyl ether/water partition coefficients of bipyridine and 1,10-phenanthroline and their iron complexes gave much higher values for the free chelators, supporting the concept that the chelators trap the iron intracellularly because of differences in the lipid solubility and, hence, membrane permeability to the free chelators and their iron complexes.
D015082:2,2'-Dipyridyl / Q000494:pharmacology; D000818:Animals; D002614:Chelating Agents / Q000494:pharmacology*; D003600:Cytosol / Q000378:metabolism; D004705:Endocytosis; D005089:Exocytosis; D007501:Iron / Q000097:blood*; D007700:Kinetics; D010618:Phenanthrolines / Q000494:pharmacology; D011817:Rabbits; D012156:Reticulocytes / Q000187:drug effects / Q000378:metabolism*; D014168:Transferrin / Q000097:blood
D002614:Chelating Agents; D010618:Phenanthrolines; D014168:Transferrin; D015082:2,2'-Dipyridyl; D007501:Iron