Disturbance of cellular iron uptake and utilisation by aluminium

Aluminium (Al) affects erythropoiesis but the real mechanism of action is s till unknown. Transferrin receptors (TfR) in K562 cells are able to bind Tf , when carrying either iron (Fe) or Al, with similar affinity. Then, the ai m of this work was to determine whether Al could interfere with the cellula r Fe uptake and utilisation. K562 cells were induced to erythroid different iation by either haemin (H) or sodium butyrate (B) and cultured with and wi thout Al. The effect of Al on cellular Fe uptake, Fe incorporation to haem and cell differentiation was studied. H- and B-stimulated cells grown in th e presence of 10 muM Al showed a reduction in the number of haemoglobinised cells (by 18% and 56%, respectively) and high amounts of Al content. Al2Tf inhibited both the Fe-59 cellular uptake and its utilisation for haem synt hesis. The removal of Al during the Fe-59 pulse, after a previous incubatio n with the metal, allowed the cells to acquire Fe quantities in the normal range or even exceeding the amounts incorporated by the respective control cells. However, the Fe incorporated to haem could not reach control values in B-stimulated cells despite enough Fe acquisition was observed after remo ving Al. Present results suggest that Al might exert either reversible or i rreversible effects on the haemoglobin synthesis depending on cellular cond itions. (C) 2001 Elsevier Science B.V. All rights reserved.