The inhibitory action of aluminum on mouse bone marrow cell growth: evidence for an erythropoietin- and transferrin-mediated mechanism.
Aluminum (Al) has been associated with anemia in chronic renal failure patients under hemodialysis as well as in Al-overloaded animals. In an attempt to elucidate further the mechanism of Al toxicity we have investigated the effect of this ion on erythropoiesis in vitro. Mouse bone marrow cells were stimulated in vitro with erythropoietin (Epo) in the presence of Al3+ ion and erythroid colony-forming units were then determined. Results of this study indicate that Al compounds (chloride and citrate) at concentrations as low as 0.37 mumol Al/l inhibit erythropoiesis in vitro through a mechanism dependent upon the availability of transferrin to bind to aluminum. This process cannot be reversed by increasing Epo doses. This inhibition only occurs in the presence of Epo at early stages during the interaction of the hormone with its target cell.
Garbossa
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G
Departamento de Quimica Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Argentina.
Gutnisky
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A
Nesse
A
A
D000535:Aluminum / Q000378:metabolism / Q000633:toxicity*; D000818:Animals; D001853:Bone Marrow / Q000187:drug effects*; D001854:Bone Marrow Cells; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D015672:Erythroid Precursor Cells / Q000187:drug effects; D004920:Erythropoiesis / Q000187:drug effects; D004921:Erythropoietin / Q000494:pharmacology*; D051379:Mice; D014168:Transferrin / Q000378:metabolism*
D014168:Transferrin; D004921:Erythropoietin; D000535:Aluminum