Effects of cell proliferation on the uptake of transferrin-bound iron by human hepatoma cells

Authors

  • Adrian W. M. Lee,

    1. Department of Physiology, School of Biomedical and Chemical Sciences, The University of Western Australia, Crawley
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  • Phillip S. Oates,

    1. Department of Physiology, School of Biomedical and Chemical Sciences, The University of Western Australia, Crawley
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  • Deborah Trinder Ph.D.

    Corresponding author
    1. School of Medicine and Pharmacology, The University of Western Australia, Fremantle Hospital, Western Australia, Australia
    2. Western Australian Institute for Medical Research, Nellands, Western Australia, Australia
    • School of Medicine and Pharmacology, The University of Western Australia, Fremantle Hospital, P.O. Box 480, Fremantle 6959, Western Australia. fax: (61) 8–9431–2977
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Abstract

The effects of cellular proliferation on the uptake of transferrin-bound iron (Tf-Fe) and expression of transferrin receptor-1 (TfR1) and transferrin receptor-2 (TfR2) were investigated using a human hepatoma (HuH7) cell line stably transfected with TfR1 antisense RNA expression vector to suppress TfR1 expression. At transferrin (Tf) concentrations of 50 nmol/L and 5 μmol/L, when Tf-Fe uptake occurs by the TfR1- and TfR1-independent (NTfR1)-mediated process, respectively, the rate of Fe uptake by proliferating cells was approximately 250% that of stationary cells. The maximum rate of Fe uptake by the TfR1- and NTfR1-mediated process by proliferating cells was increased to 200% and 300% that of stationary cells, respectively. The maximum binding of Tf by both TfR1- and NTfR1-mediated processes by proliferating cells was increased significantly to 160% that of stationary cells. TfR1 and TfR2-α protein levels expressed by proliferating cells was observed to be approximately 300% and 200% greater than the stationary cells, respectively. During the proliferating growth phase, expression of TfR1 messenger RNA (mRNA) increased to 300% whereas TfR2-α mRNA decreased to 50% that of stationary cells. In conclusion, an increase in Tf-Fe uptake by TfR1-mediated pathway by proliferating cells was associated with increased TfR1 mRNA and protein expression. An increase in Tf-Fe uptake by NTfR1-mediated pathway was correlated with an increase in TfR2-α protein expression but not TfR2-α mRNA. In concluion, TfR2-α protein is likely to have a role in the mediation of Tf-Fe uptake by the NTfR1 process by HuH7 hepatoma cell in proliferating and stationary stages of growth. (Hepatology 2003;38:967–977).

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