Acquisition, storage and release of iron by cultured human hepatoma cells

Background/Aims: The recovery from iron overload is hampered by the limited number of pathways and therapeutic agents available for the augmentation of iron secretion/excretion. The present study was aimed to investigate the process of iron storage and release by cultured human hepatoma cells, the role of transferrin receptors and ferritin in this process as well as the effect of iron chelators. Methods: We followed the acquisition, storage and release of iron by cultured cells HepG2 and Hep3B by biochemical means and electron microscopy. Results: The uptake of iron from diferric transferrin (Trf) was extremely low, while iron as ferric-ammonium-citrate (FAC) was taken up readily, especially by Hep3B cells. Up to 80% of the iron taken up by hepatoma cells was released to the medium. The rate of spontaneous iron release depended on the extent of iron loading. ApoTrf and deferoxamine facilitated release after 1- and 7-day iron-exposure. Up to a third of the radio-iron released from the cells was associated with ferritin. The release of ferritin-iron was not enhanced by either deferoxamine or Trf. Conclusions: Ferritin-iron release appeared to be an important mechanism of iron discarding in cultured human hepatoma cells, independent of the activity of chelating agents.