The process of cellular uptake of iron from transferrin

Bakøy, O. E.; Thorstensen, Ketil

doi:10.1111/j.1432-1033.1994.tb18847.x

Cited by 8 publications

(3 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Several studies have indicated the presence of a nonspecific, non-receptor-mediated iron-uptake mechanism [2-41. Recently, it was suggested that the main difference in iron-uptake mechanism between hepatocytes and reticulocytes was the former's ability to utilize pinocytosis for iron uptake from transferrin [8]. Many components taken up by cells via pinocytosis enter the lysosomal compartment and are subsequently degraded [21].…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Uptake of Iron from N‐Terminal Half‐Transferrin by Isolated Rat Hepatocytes Evidence of Transferrin‐Receptor‐Independent Iron Uptake

Thorstensen¹,

Trinder²,

Zak³

et al. 1995

European Journal of Biochemistry

Self Cite

View full text Add to dashboard Cite

The aim of the present study was to determine if human N-terminal half-transfenin (N-fragment), prepared by thermolysin cleavage of difemc transferrin, would bind to the rat hepatocyte transfenin receptor and donate iron to the cell. Competition experiments between 'Z51-labelled N-fragment and diferric transferrin revealed no receptor binding of the half-transferrin. Still, the N-fragment delivered iron to the cells in amounts approximately 30-fold above what could be accounted for by uptake of the fragment itself. The rate of celluar iron uptake from the fragment was comparable to what is seen with the intact transferrin. The uptake of '251-labelled N-fragment was not inhibited by excess non-radioactive diferric transferrin. By comparison, the uptake of 59Fe from the N-fragment was inhibited 70% by excess nonradioactive diferric transferrin. This suggests that iron derived from diferric transferrin competes with the iron derived from the N-fragment for a common transport pathway. Although some cellular degradation of the N-fragment occurred, the extent of degradation was too low to explain the amount of iron accumulated by the cells. The results show that the hepatocyte has an effective transferrin-receptor-independent mechanism for accumulation of iron from transfenin.Keywords: half-transferrin; hepatocyte; iron; transferrin receptor.For the majority of cell types, the mechanism of cellular uptake of iron from transferrin is receptor-mediated endocytosis. However, at least for the hepatocyte, alternative mechanisms appear to exist [I]. Non-specific mechanisms such as adsorptive endocytosis or pinocytosis were long since suggested [2-71, and recently pinocytosis was shown to possibly be a major factor in hepatocyte transferrin iron uptake [S]. Recently, studies with cell types other than hepatocytes, e.g. fibroblasts, melanoma cells, bone marrow macrophages, reticulocytes, or transferrin-receptor-depleted Chinese hamster ovary (CHO) cells, have also suggested the presence of a transferrin-receptor-independent route of iron uptake from transfemn 19-13]. In addition, a plasma membrane process driven by an oxidoreductase has been described, but remains uncertain and controversial 114, 151. Thus, receptor-mediated endocytosis may not be the exclusive mechanism by which cells acquire iron from transferrin.To investigate a receptor-independent mechanism for transferrin iron uptake without interfering with the cells by use of inhibitors, one would need either a cell type without any transferrin receptors, or a transferrin that does not bind to the cellular receptors. The fact that transferrin may be proteolytically cleaved to yield N-terminal or C-terminal half-transferrins (N-or C-fragments) that have retained the characteristics of the intact protein with regard to iron binding [16, 171, The present study has examined the interaction of the Nterminal half-transferrin with isolated hepatocytes in terms of receptor binding, and the cell's ability to take up iron from the fragment. We show that the isolated hepatocyt...

show abstract

Section: Discussionmentioning

confidence: 99%

“…By utilizing a computer program [8] the uptake of '%labelled N-fragment could be simulated with rate constants similar to those published for pinocytosis in hepatocytes. This argues in favour of pinocytosis as the mechanism.…”

Section: Discussionmentioning

confidence: 99%

Uptake of Iron from N‐Terminal Half‐Transferrin by Isolated Rat Hepatocytes Evidence of Transferrin‐Receptor‐Independent Iron Uptake

Thorstensen¹,

Trinder²,

Zak³

et al. 1995

European Journal of Biochemistry

Self Cite

View full text Add to dashboard Cite

show abstract

“…Also, transferrin may be internalized by a low affinity system, possibly pinocytotic (Hodgson et al, 1994), that is receptor independent and capable of delivering iron to haemoglobin. The latter pathway appears to be a minor pathway in reticulocytes (Bakoy & Thorstensen, 1994).…”

Section: Discussionmentioning

confidence: 91%

The alternate iron transport pathway: mobilferrin and integrin in reticulocytes

et al. 1997

View full text Add to dashboard Cite

Iron transport in reticulocytes is known to occur via the well‐described transferrin‐receptor–endosome pathway. An alternative pathway for iron transport independent of transferrin has been postulated in reticulocytes and other cells. Transport of iron into reticulocytes from ferric citrate solutions was shown to be saturable and independent of transferrin. During transport of iron from ferric citrate, both cell surface integrins, and a soluble protein, mobilferrin, were labelled. This demonstrated that the reticulocyte transferrin independent pathway for iron transport involved integrins and mobilferrin similar to intestinal absorptive cells. This pathway would be expected to transport iron into cells under conditions of iron overload and was capable of providing iron for haemoglobin synthesis. Mobilferrin was also radiolabelled when radioiron labelled transferrin was incubated with reticulocytes and this occurred with a different time course than was observed following reticulocyte exposure to radiolabelled ferric citrate. This suggested that mobilferrin may serve as an intermediary in both pathways.

show abstract