pyridoxal-isonicotinoyl-hydrazone and Leukemia--Promyelocytic--Acute

We have previously shown that human leukemic HL60 cells release from their surface a soluble form of the transferrin receptor. Because of the regulatory role of iron in transferrin receptor expression, we have now examined the relationship between iron and the release of soluble transferrin receptor from HL60 cells. Cells grown in serum-free, transferrin-free medium containing iron-pyridoxal isonicotinoyl hydrazone (Fe-PIH) displayed approximately 70% less iodine 125-labeled transferrin surface binding and released 60% less soluble transferrin receptor than cells grown in serum-supplemented medium. Incubation of cells with increasing concentrations of Fe-PIH resulted in a progressive decrease in the release of soluble transferrin receptor over 18 hours of incubation. In contrast, receptor release was increased after incubation of cells with the iron chelator deferoxamine. This effect was completely blocked by cycloheximide. Transferrin receptor release from cells over 2 hours was unaffected by the presence of transferrin-iron, suggesting that transferrin receptor release occurs independent of the cellular handling of its ligand. Exposure of cells to phorbol myristate acetate resulted in a decrease in cell surface transferrin receptor and a decrease in the release of soluble transferrin receptor. Our studies show that transferrin receptor release from HL60 cells changes during iron excess or iron deficiency and that these changes are the result of alterations in cell surface transferrin receptor density. Our studies suggest that elevated serum transferrin receptor levels seen in clinical iron deficiency reflect corresponding increases in transferrin receptors at the cellular level.

Topics: Cell Membrane; Chromatography, Gel; Humans; Iron; Isoniazid; Leukemia, Promyelocytic, Acute; Ligands; Pyridoxal; Receptors, Transferrin; Solubility; Tumor Cells, Cultured