Abstract

Introduction

Materials & Methods

Results

Discussion & Conclusion

References

Discussion
Board

Previously, we demonstrated that uptake of non-transferrin bound Fe (NTBI) by cultured human hepatocarcinoma (HepG2) cells was mediated by a specific, saturable and temperature-sensitive process that was up-regulated in a dose-dependent fashion by Fe loading. It has been suggested that Fe-catalyzed free radical formation may contribute to this up-regulation via damaging plasma membrane integrity; however, membrane permeability was maintained with a minimal leakage of radiolabelled Fe or lactate dehydrogenase over 24 h . Trypan blue dye exclusion also showed viability was unaffected by Fe loading 3 days in the presence of 5-80 micrograms Fe /ml extracellular Fe, the time of maximal transport up-regulation. Chelation with deferroxamine or deferiprone reversed up-regulation of NTBI uptake within hours, a time considerably shorter than that required for membrane repair. These data are more consistent with carrier mediated uptake coupled to the chelatable intracellular Fe pool, possibly through the iron response element binding protein, IRP-1. This hypothesis is currently being tested utilizing transfection with IRP-1 antisense expression vectors.

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Presentation Number SAparkes0715
Keywords: iron transport, chelation, NTBI, IRP, hepatocyte