Effect of iron chelators on the transferrin receptor in K562 cells.
Delivery of iron to K562 cells by diferric transferrin involves a cycle of binding to surface receptors, internalization into an acidic compartment, transfer of iron to ferritin, and release of apotransferrin from the cell. To evaluate potential feedback effects of iron on this system, we exposed cells to iron chelators and monitored the activity of the transferrin receptor. In the present study, we found that chelation of extracellular iron by the hydrophilic chelators desferrioxamine B, diethylenetriaminepentaacetic acid, or apolactoferrin enhanced the release from the cells of previously internalized 125I-transferrin. Presaturation of these compounds with iron blocked this effect. These chelators did not affect the uptake of iron from transferrin. In contrast, the hydrophobic chelator 2,2-bipyridine, which partitions into cell membranes, completely blocked iron uptake by chelating the iron during its transfer across the membrane. The 2,2-bipyridine did not, however, enhance the release of 125I-transferrin from the cells, indicating that extracellular iron chelation is the key to this effect. Desferrioxamine, unlike the other hydrophilic chelators, can enter the cell and chelate an intracellular pool of iron. This produced a parallel increase in surface and intracellular transferrin receptors, reaching 2-fold at 24 h and 3-fold at 48 h. This increase in receptor number required ongoing protein synthesis and could be blocked by cycloheximide. Diethylenetriaminepentaacetic acid or desferrioxamine presaturated with iron did not induce new transferrin receptors. The new receptors were functionally active and produced an increase in 59Fe uptake from 59Fe-transferrin. We conclude that the transferrin receptor in the K562 cell is regulated in part by chelatable iron: chelation of extracellular iron enhances the release of apotransferrin from the cell, while chelation of an intracellular iron pool results in the biosynthesis of new receptors.
D001059:Apoproteins / Q000494:pharmacology*; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D003676:Deferoxamine / Q000494:pharmacology*; D006801:Humans; D007501:Iron / Q000378:metabolism; D007502:Iron Chelating Agents; D007700:Kinetics; D007781:Lactoferrin / Q000494:pharmacology*; D007782:Lactoglobulins / Q000494:pharmacology*; D015470:Leukemia, Myeloid, Acute; D004369:Pentetic Acid / Q000494:pharmacology*; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism*; D011990:Receptors, Transferrin; D014168:Transferrin / Q000378:metabolism*
D001059:Apoproteins; D007502:Iron Chelating Agents; D007782:Lactoglobulins; D011956:Receptors, Cell Surface; D011990:Receptors, Transferrin; D014168:Transferrin; C039223:apolactoferrin; D004369:Pentetic Acid; D007501:Iron; D007781:Lactoferrin; D003676:Deferoxamine