HFE downregulates iron uptake from transferrin and induces iron-regulatory protein activity in stably transfected cells

• Verfasst von: Riedel, Hans-Dieter [VerfasserIn]
• Verfasst von: Muckenthaler, Martina [VerfasserIn]
• Verfasst von: Gehrke, Sven [VerfasserIn]
• Verfasst von: Mohr, I. [VerfasserIn]
• Verfasst von: Brennan, K. [VerfasserIn]
• Verfasst von: Herrmann, Thomas [VerfasserIn]
• Verfasst von: Fitscher, Barbara [VerfasserIn]
• Verfasst von: Hentze, Matthias W. [VerfasserIn]
• Verfasst von: Stremmel, Wolfgang [VerfasserIn]
• Titel: HFE downregulates iron uptake from transferrin and induces iron-regulatory protein activity in stably transfected cells
• Verf.angabe: H.D. Riedel, M.U. Muckenthaler, S.G. Gehrke, I. Mohr, K. Brennan, T. Herrmann, B.A. Fitscher, M.W. Hentze, and W. Stremmel
• Jahr: 1999
• Umfang: 7 S.
• Fussnoten: Available online 14 December 2020 ; Gesehen am 12.05.2021
• Titel Quelle: Enthalten in: Blood
• Ort Quelle: Washington, DC : American Society of Hematology, 1946
• Jahr Quelle: 1999
• Band/Heft Quelle: 94(1999), 11, Seite 3915-3921
• ISSN Quelle: 1528-0020
• DOI: doi:10.1182/blood.V94.11.3915
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1757730850

Abstract

Hereditary hemochromatosis (HH) is a common autosomal-recessive disorder of iron metabolism. More than 80% of HH patients are homozygous for a point mutation in a major histocompatibility complex (MHC) class I type protein (HFE), which results in a lack of HFE expression on the cell surface. A previously identified interaction of HFE and the transferrin receptor suggests a possible regulatory role of HFE in cellular iron absorption. Using an HeLa cell line stably transfected with HFE under the control of a tetracycline-sensitive promoter, we investigated the effect of HFE expression on cellular iron uptake. We demonstrate that the overproduction of HFE results in decreased iron uptake from diferric transferrin. Moreover, HFE expression activates the key regulators of intracellular iron homeostasis, the iron-regulatory proteins (IRPs), implying that HFE can affect the intracellular “labile iron pool.” The increase in IRP activity is accompanied by the downregulation of the iron-storage protein, ferritin, and an upregulation of transferrin receptor levels. These findings are discussed in the context of the pathophysiology of HH and a possible role of iron-responsive element (IRE)-containing mRNAs.