Abstract

Introduction

Materials & Methods

Results

Discussion & Conclusion

References

Discussion
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A role for ceruloplasmin (Cp) in iron homeostasis is suggested by its ferroxidase activity, by the correction of certain experimental anemias by Cp, by Cp stimulation of iron efflux from perfused organs, and by hemochromatosis in aceruloplasminemia patients. These findings are consistent with a role for Cp in tissue iron efflux. However, recent studies in yeast indicate that the Cp homologue Fet3p is required for iron uptake. We have investigated the specific role of Cp in iron metabolism in vertebrate cells. Cp enhanced iron uptake in iron-deficient (but not iron-sufficient) HepG2 cells. The uptake did not require transferrin or its cell-surface receptor. Cp was synthesized by HepG2 cells in an amount sufficient to cause iron uptake. Since key proteins that regulate vertebrate iron homeostasis are themselves regulated by iron, we examined whether Cp was similarly regulated. Iron depletion of HepG2 cells increased Cp synthesis and Cp transcript levels 5-fold, a finding consistent with a role in cell iron uptake. In contrast to the post-transcriptional regulation of several proteins involved in iron metabolism, Cp was transcriptionally regulated. Thus our cellular studies which show a role of Cp in iron uptake, and previous organ culture and in vivo studies which suggest a role in tissue iron release, present a paradox that awaits resolution.

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Presentation Number SAfox0706
Keywords: ceruloplasmin, iron, transport, transcription, liver