pyridoxal-isonicotinoyl-hydrazone and Leukemia--Erythroblastic--Acute

Transferrin bound to K 562 cells at 4 degrees C was internalized quickly on temperature shift to 37 degrees C. Endosomes were isolated according to two different procedures. The endosome fraction was shown to be heterogeneous and consisted of two vesicle populations, differing in density properties and iron content. Iron was partially released from endosomes to the supernatant after 3 and 5 min endocytosis. Isolated endosomes, still capable of internal acidification, did not release iron on incubation with ATP. However, endosomes did release iron on incubation with the iron chelator pyridoxal-isonicotinoyl hydrazone. Gel-filtration of solubilized endosomes demonstrated the presence of the transferrin-transferrin receptor complexes, free transferrin and free low molecular weight iron.

Topics: Adenosine Triphosphate; Cell Fractionation; Cell Line; Centrifugation; Endocytosis; Endosomes; Humans; Iron; Iron Chelating Agents; Iron Radioisotopes; Isoniazid; Leukemia, Erythroblastic, Acute; Pyridoxal; Transferrin

Iron metabolism is important for proliferation, but in erythroid cells it is also required for haem synthesis. In erythroleukaemia cells, there is both a continuous proliferation and a synthesis of haem, and these cell lines are therefore especially interesting for studies on iron metabolism. Iron can be efficiently delivered intracellularly by certain chelators which bypass the transferrin-receptor-mediated pathway of iron uptake. We now show that the human erythroleukaemia cell line, HEL, displays a greatly enhanced cell proliferation when cultured in the presence of the lipophilic iron chelator, ferric pyridoxal isonicotinoyl hydrazone. The proliferation is not accompanied by an increase in haemoglobin synthesis. The response is apparently not typical for all erythroleukaemia cells, since a similar cell line, K 562, did not respond to the chelator by enhanced proliferation.

Topics: Cell Cycle; Cell Line; Chelating Agents; Humans; Iron; Iron Chelating Agents; Isoniazid; Leukemia, Erythroblastic, Acute; Pyridoxal; Transferrin