Iron transport in a lymphoid cell line with the hemochromatosis C282Y mutation.

Blood
C R Chitambar, J P Wereley

Abstract

The gene for hemochromatosis (HFE) is expressed in a variety of cells, including those not thought to be affected by this disease. The impact of HFE on iron transport was examined in B-lymphoid cell lines developed from a patient with hemochromatosis with the HFE C282Y mutation (C282Y cells) and an individual with the wild-type HFE gene (WT cells). Whereas both cell lines expressed HFE protein, C282Y cells displayed less HFE protein at the cell surface. Transferrin receptor (TfR) number was 2- to 3-fold greater in WT cells than in C282Y cells, while TfR affinity for transferrin (Tf) was slightly lower in C282Y cells. TfR distribution between intracellular and cell-surface compartments was similar in both cell lines. Iron uptake per cell was greater in WT cells but was not increased proportional to TfR number. When considered relative to cell-surface TfR number, however, iron uptake and Tf internalization were actually greater in C282Y cells. Surprisingly, Tf-independent iron uptake was also significantly greater in C282Y cells than in WT cells. The ferritin content of C282Y cells was approximately 40% that of WT cells. Exposure of cells to pro-oxidant conditions in culture led to a greater inhibition of proliferation in C282Y c...Continue Reading

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Citations

Nov 26, 2002·Journal of Hepatology·Giovanna FabioGemino Fiorelli
Apr 23, 2003·Free Radical Biology & Medicine·Richard G StevensLyle B Sasser
Mar 19, 2005·Genetics in Medicine : Official Journal of the American College of Medical Genetics·M Tevfik DorakMark Worwood
Nov 17, 2006·Leukemia & Lymphoma·Assunta ViolaFelicetto Ferrara
Jul 11, 2006·International Journal of Cancer. Journal International Du Cancer·Christopher R ChitambarJanine P Wereley
Mar 20, 2014·European Journal of Immunology·Alexandre ReubenRéjean Lapointe
May 11, 2002·Leukemia & Lymphoma·M Tevfik DorakMark Worwood

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