title: Substantial changes of cellular iron homeostasis during megakaryocytic differentiation of K562 cells.
abstract: We investigated the remodeling of iron metabolism during megakaryocytic development of K562 cells. Differentiation was successfully verified by increase of the megakaryocytic marker CD61 and concomitant decrease of the erythroid marker γ-globin. The reduction of erythroid properties was accompanied by changes in the cellular iron content and in the expression of proteins regulating cellular iron homeostasis. Independent of available inorganic or transferrin-bound extracellular iron, total intracellular iron increases while the iron-to-protein ratio decreases. The iron exporter ferroportin is downregulated within 1-6 h, followed by downregulation of transferrin receptor-1 (TfR1) and ferritin heavy chain (H-ferritin) mainly after 24-48 h. The hemochromatosis protein-1, a ligand of TfR1, peaked after 24 h. All effects were independent of iron supply with the exception of H-ferritin, which was restored by excess iron. While alterations of CD61, TfR1 and ferritin expression were revoked by a protein kinase C inhibitor, downregulation of ferroportin remained unaffected.
authors.affiliation: Zentralinstitut für Laboratoriumsmedizin und Pathobiochemie, Charité- Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Wandzik
authors.forename: Claudia
authors.initials: C
authors.lastname: Zahn
authors.forename: Katrin
authors.initials: K
authors.lastname: Dassler
authors.forename: Hendrik
authors.initials: H
authors.lastname: Fuchs
mesh_terms: D015703:Antigens, CD / Q000235:genetics; D001052:Apoferritins / Q000235:genetics; D015153:Blotting, Western; D027682:Cation Transport Proteins / Q000235:genetics; D002454:Cell Differentiation; D015870:Gene Expression; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I / Q000235:genetics; D006706:Homeostasis; D006801:Humans; D039661:Integrin beta3 / Q000235:genetics; D007501:Iron / Q000378:metabolism*; D020014:K562 Cells; D008533:Megakaryocytes / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics; D016133:Polymerase Chain Reaction; D011493:Protein Kinase C / Q000378:metabolism; D011990:Receptors, Transferrin / Q000235:genetics; D034061:Thrombopoiesis; D055545:gamma-Globins / Q000235:genetics; D000098742:Ferroportin
chemical_list: D015703:Antigens, CD; C068126:CD71 antigen; D027682:Cation Transport Proteins; C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D039661:Integrin beta3; D008565:Membrane Proteins; D011990:Receptors, Transferrin; D055545:gamma-Globins; D000098742:Ferroportin; D001052:Apoferritins; D007501:Iron; D011493:Protein Kinase C