Iron transport in a lymphoid cell line with the hemochromatosis C282Y mutation.
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 cells than in WT cells. Our results indicate that in this B-lymphoid cell line, the HFE C282Y mutation affects both Tf-dependent and -independent iron uptake and enhances cell sensitivity to oxidative stress. The role of HFE in iron uptake by B cells may extend beyond its known interaction with the TfR.
Chitambar
C R
CR
Division of Hematology/Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee 53226, USA. chitambr@mcw.edu
Wereley
J P
JP
D001402:B-Lymphocytes / Q000378:metabolism*; D002460:Cell Line; D006432:Hemochromatosis / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D017136:Ion Transport / Q000235:genetics; D007501:Iron / Q000378:metabolism*; D009154:Mutation
D007501:Iron