TY - JOUR
T1 - Overexpression of the hereditary hemochromatosis protein, HFE, in HeLa cells induces an iron-deficient phenotype
AU - Corsi, Barbara
AU - Levi, Sonia
AU - Cozzi, Anna
AU - Corti, Angelo
AU - Altimare, Domenico
AU - Albertini, Alberto
AU - Arosio, Paolo
PY - 1999/10/22
Y1 - 1999/10/22
N2 - A transfectant HeLa cell clone expressing HFE under the control of a tetracycline-repressible promoter was generated. HFE expression was fully repressed by the presence of doxycycline, while it was strongly induced by growth in the absence of doxycycline. HFE accumulation was accompanied by a large (~10-fold) decrease in H- and L-ferritin levels, by a ~3-4-fold increase in transferrin receptor, and a ~2-fold increase in iron regulatory protein activity. These indices of cellular iron deficiency were reversed by iron supplementation complexes. The overexpressed HFE immunoprecipitated together with transferrin receptor, indicating a physical association which is the likely cause for the observed ~30% decrease in 55Fe-transferrin incorporation after 18 h incubation. In the HFE-expressing cells the reduction in transferrin-mediated iron incorporation was partially compensated by a ~30% increase in non-transferrin iron incorporation from 55Fe-NTA, evident after prolonged, 18 h, incubations. The findings indicate that HFE binding to transferrin receptor reduces cellular iron availability and regulates the balance between transferrin-mediated and non-transferrin-mediated cellular iron incorporation. Copyright (C) 1999 Federation of European Biochemical Societies.
AB - A transfectant HeLa cell clone expressing HFE under the control of a tetracycline-repressible promoter was generated. HFE expression was fully repressed by the presence of doxycycline, while it was strongly induced by growth in the absence of doxycycline. HFE accumulation was accompanied by a large (~10-fold) decrease in H- and L-ferritin levels, by a ~3-4-fold increase in transferrin receptor, and a ~2-fold increase in iron regulatory protein activity. These indices of cellular iron deficiency were reversed by iron supplementation complexes. The overexpressed HFE immunoprecipitated together with transferrin receptor, indicating a physical association which is the likely cause for the observed ~30% decrease in 55Fe-transferrin incorporation after 18 h incubation. In the HFE-expressing cells the reduction in transferrin-mediated iron incorporation was partially compensated by a ~30% increase in non-transferrin iron incorporation from 55Fe-NTA, evident after prolonged, 18 h, incubations. The findings indicate that HFE binding to transferrin receptor reduces cellular iron availability and regulates the balance between transferrin-mediated and non-transferrin-mediated cellular iron incorporation. Copyright (C) 1999 Federation of European Biochemical Societies.
KW - Hemochromatosis
KW - HFE protein
KW - Iron metabolism
KW - Recombinant protein
KW - Transferrin receptor
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U2 - 10.1016/S0014-5793(99)01330-7
DO - 10.1016/S0014-5793(99)01330-7
M3 - Article
C2 - 10571078
AN - SCOPUS:0032866573
VL - 460
SP - 149
EP - 152
JO - FEBS Letters
JF - FEBS Letters
SN - 0014-5793
IS - 1
ER -