Expression of the Hereditary Hemochromatosis Protein HFE Increases Ferritin Levels by Inhibiting Iron Export in HT29 Cells

Iron is essential for life in almost all organisms and, in mammals, is absorbed through the villus cells of the duodenum. Using a human colonic carcinoma cell line that has many duodenal characteristics, HT29, we show that genes involved in intestinal iron transport are endogenously expressed. When...

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Veröffentlicht in:The Journal of biological chemistry 2004-06, Vol.279 (24), p.25085-25092
Hauptverfasser: Davies, Paige S., Enns, Caroline A.
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description Iron is essential for life in almost all organisms and, in mammals, is absorbed through the villus cells of the duodenum. Using a human colonic carcinoma cell line that has many duodenal characteristics, HT29, we show that genes involved in intestinal iron transport are endogenously expressed. When stably transfected to express the hereditary hemochromatosis protein HFE these cells have increased ferritin levels. We demonstrate that this is not due to an effect on the transferrin (TF)-mediated iron uptake pathway but rather due to inhibition of iron efflux from the cell. The effect of HFE was independent of its interaction with TF receptor 1 as indicated by similar results using both the wild type HFE and the W81A mutant that binds TF receptor 1 with greatly reduced affinity. HFE expression did not affect the mRNA levels of most of the genes involved in iron absorption that were tested; however, it did correspond to a decrease in hephaestin message levels. These results point to a role for HFE in inhibition of iron efflux in HT29 cells. This is a distinct role from that in HeLa and human embryonic kidney 293 cells where HFE has been shown to inhibit TF-mediated iron uptake resulting in decreased ferritin levels. Such a distinction suggests a multifunctional role for HFE that is dependent upon expression levels of proteins involved in iron transport.
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subjects Antigens, CD
Biological Transport
Cell Polarity
Ferritins - blood
Hemochromatosis Protein
Histocompatibility Antigens Class I - physiology
Homeostasis
HT29 Cells
Humans
Iron - metabolism
Membrane Proteins - physiology
Receptors, Transferrin - physiology
RNA, Messenger - analysis
title Expression of the Hereditary Hemochromatosis Protein HFE Increases Ferritin Levels by Inhibiting Iron Export in HT29 Cells
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