Uptake and intracellular distribution of iron from transferrin and chelators in erythroid cells.
Iron chelators of different physicochemical properties were studied for their ability to donate iron in vitro to uninduced K562 cells, human bone marrow cells and purified human erythroblasts. To a large extent uptake was found to be related to lipophilicity and those chelators able to deliver iron to the cells in significant amounts were also able to deliver iron to ferritin and haem. Some differences in the distribution of iron delivered was observed but no chelator showed exclusive delivery to or rejection of a particular cellular iron compartment. Several chelators could probably substitute for transferrin and be used to probe metabolic events subsequent to iron removal from transferrin. Two chelators which were excellent iron donors were also found to cause considerable inhibition of iron incorporation into haem from transferrin. The implications of this for in vivo toxicity are briefly discussed.
Kontoghiorghes
G J
GJ
Royal Free Hospital School of Medicine, London, UK.
May
A
A
D001692:Biological Transport / Q000187:drug effects; D002460:Cell Line; D004900:Erythroblasts / Q000187:drug effects / Q000378:metabolism*; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000378:metabolism*; D006418:Heme / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007501:Iron / Q000378:metabolism*; D007502:Iron Chelating Agents / Q000378:metabolism / Q000494:pharmacology*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive; D014168:Transferrin / Q000378:metabolism*
D007502:Iron Chelating Agents; D014168:Transferrin; D006418:Heme; D007501:Iron