title: Iron-chelator complexes as iron sources for early developing human erythroid precursors.
abstract: Developing erythroid cells are dependent on transferrin (Tf) to acquire iron in amounts sufficient for hemoglobin production. Previously, we showed that although these cells cannot grow in culture in the absence of Tf, ferritin (Ft) can substitute Tf to some extent and support the development of hemoglobin-containing cells. In the current study, we investigated the ability of various iron sources to replace Tf in cultures of normal human erythroid precursors. The results showed that whereas Ft and hemin supported erythroid cell proliferation and hemoglobinization in Tf-free cultures to some extent, ferric amonium citrate and iron complexed with several chelators had little or no effect. Although salicylaldehyde-isonicotinoyl-hydrazone, which is a tridentate lipid-soluble chelator, complexed with iron increased both cytosolic and mitochondrial labile iron pools, it failed to support heme synthesis and did not decrease the surface Tf receptors, suggesting that its iron is not recognized by the cells. Moreover, this iron-chelator complex did not support erythroid precursor proliferation and hemoglobinization. Thus, although under normal conditions, Tf is the major route of iron uptake, Ft and hemin, but not iron-chelator complexes, may serve as alternative iron sources under Tf-poor conditions.
authors.affiliation: Department of Human Nutrition and Metabolism, Faculty of Medicine, The Hebrew University, Jerusalem, Israel.
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Leimberg
authors.forename: Eugenia
authors.initials: E
authors.lastname: Prus
authors.forename: Gabriela
authors.initials: G
authors.lastname: Link
authors.forename: Eitan
authors.initials: E
authors.lastname: Fibach
authors.forename: Abraham M
authors.initials: AM
authors.lastname: Konijn
mesh_terms: D000447:Aldehydes / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D015672:Erythroid Precursor Cells / Q000187:drug effects* / Q000378:metabolism; D005290:Ferric Compounds / Q000494:pharmacology*; D005293:Ferritins / Q000494:pharmacology; D006427:Hemin / Q000494:pharmacology; D006454:Hemoglobins / Q000096:biosynthesis; D006801:Humans; D006835:Hydrazones / Q000494:pharmacology*; D007501:Iron / Q000378:metabolism*; D007502:Iron Chelating Agents / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology*
chemical_list: D000447:Aldehydes; D005290:Ferric Compounds; D006454:Hemoglobins; D006835:Hydrazones; D007502:Iron Chelating Agents; D000644:Quaternary Ammonium Compounds; C413684:salicylaldehyde isonicotinoyl hydrazone; D006427:Hemin; D005293:Ferritins; D007501:Iron; C013531:ferric ammonium citrate