Substantial changes of cellular iron homeostasis during megakaryocytic differentiation of K562 cells |
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Authors: | Wandzik Krzysztof Zahn Claudia Dassler Katrin Fuchs Hendrik |
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Institution: | 1. Zentralinstitut für Laboratoriumsmedizin und Pathobiochemie, Charité– Universit?tsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany;2. Present address: Bayer Schering Pharma AG, Targeted Biological Therapeutics, Oncology Berlin, D‐13353 Berlin, Germany. |
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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. |
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Keywords: | ferroportin human hemochromatosis protein‐1 iron metabolism disorders megakaryocytopoiesis transferrin receptor |
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