Transferrin and iron release from rat hepatocytes in culture

Abstract

The regulation of transferrin and iron release from the liver was studied using adult rat hepatocytes in primary monolayer culture. The cells were prelabeled by incubation with rat transferrin doubly labeled with iodine-125 and iron-59. Approximately 50% of the 125I-transferrin but only 10% of the iron-59 taken up by the cells was released during reincubation for 24 h. Less than 10% of the refluxed transferrin was catabolized as indicated by the protein-free iodine-125 values. These results suggest that at least part of iron uptake by hepatocytes is mediated by the reversible binding of transferrin in a manner comparable with erythroid cells and placenta. However, several iron chelators mobilized hepatic iron, in contrast to erythroid cells. Apotransferrin and desferrioxamine released a maximum of about 20% iron-59 with little effect on transferrin binding. A greater proportion of the iron-59 was available for chelation after shorter uptake times (1-2 h) than longer times. Hence, there are at least three iron compartments in hepatocytes in culture: rapidly refluxing iron that may be transferrin bound, a fixed pool, and a chelatable pool that may represent iron in transit between plasma transferrin and ferritin.

Low Intracellular Iron Increases the Stability of Matriptase-2

“…The increase in TfR1 is an indirect indicator of iron deprivation. This is consistent with the previous observations that apo-Tf facilitates iron release from hepatic cells (37,38) and the hypothesis that excess apo-Tf reduces the cellular iron uptake by increasing the amount of monoferric Tf (39). Each molecule of monoferric Tf delivers less iron than holo-Tf into the cells.…”

“…Apo-Tf was used to chelate the non-Tf-bound iron in the medium. Previous studies indicate that apo-Tf facilitates iron release from hepatic cells (37,38) and reduces iron uptake into the immature erythroid cells of mice and the cultured K562 cells (39). Incubation with apo-Tf led to increases in both total MT2 (input) and biotinylated cell surface MT2 (Fig.…”

Limited iron export by hepatocytes contributes to hepatic iron-loading in the Hfe knockout mouse

“…The restricted capacity to export Fe in mouse hepatocytes confirms previous studies using rat hepatocytes [7,8,16,17]. Fe release by hepatocytes was rapid in the first 15 min but reached a plateau by 1 h. These results imply that there is a limited labile intracellular Fe pool from which the cells can mobilise Fe.…”

“…2(C)) suggesting that the size of the intracellular Fe pool was greater and/or more accessible for mobilisation during short incubations. It is likely that after longer incubation times more of the Fe taken up was incorporated into the Fe storage protein ferritin rendering the Fe less accessible for release as reported by Baker et al [8].…”

“…Hepatocytes and hepatoma cells generally have a low capacity to mobilise Fe [7][8][9]. Fe release is temperaturedependent [10] and is enhanced by the presence of serum, apo-transferrin and various chelators [7,10].…”