Aluminum exposure affects transferrin-dependent and -independent iron uptake by K562 cells

PÉREZ GLADYS; PREGI NICOLÁS; VITTORI DANIELA; DI RISIO CECILIA; GARBOSSA GRACIELA; NESSE ALCIRA

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH

Elsevier

Año: 2005 vol. 1745 p. 124 - 130

0167-4889

Aluminum (Al) and iron (Fe) share several physicochemical characteristics and they both bind to transferrin (Tf), entering the cell via Tfreceptors (TfR). Previously, we found similar values of affinity constant for the binding of TfR to Tf carrying either Al or Fe. The competitiveinteraction between both metals prevented normal Fe incorporation into K562 cells and triggered the upregulation of Fe transport. In thepresent work we demonstrated that Al modified Fe uptake without affecting the expression of Tf receptors. Both TfR and TfR2 mRNAlevels, evaluated by RT-PCR, and TfR antigenic sites, analyzed by flow cytometry, were found unchanged after Al exposure. In turn, Al didinduce upregulation of non-Tf bound Fe (NTBI) uptake. This modulation was not due to intracellular Fe decrease since NTBI transportproved not to be regulated by Fe depletion. Unlike its behavior in the presence of Tf, Al was unable to compete with NTBI uptake, suggestingthat both metals do not share the same alternative transport pathway. We propose that Al interference with TfR-mediated Fe incorporationmight trigger the upregulation of NTBI uptake, an adaptation aimed at incorporating the essential metal required for cellular metabolismwithout allowing the simultaneous access of a potentially toxic metal.