Role of the sodium-dependent phosphate co-transporters and of the phosphate complexes of uranyl in the cytotoxicity of uranium in LLC-PK1 cells

Abstract

It has been suggested that uranium uptake and toxicity could be mediated by endocytosis and/or the type IIa sodium-dependent phosphate cotransporter (NaPi-IIa). The aim of this study was therefore to characterize in vitro the role of these two cellular mechanisms in the uptake and toxicity of low (200–3200nM) and high (0.5 and 0.8mM) concentrations of uranium, respectively. At low concentrations, uranium uptake in LLC-PK1 cells was saturable (Vmax 5 3.09 ± 0.22 ng/mg protein) and characterized by a K0.5 of 1022 ± 63nM and a Hill coefficient of 3.0 ± 0.4. The potential involvement of endocytosis and NaPi-IIa in the uptake of uranium was assessed by the use of various drugs and culture conditions known to alter their relative activity, and 233uranium uptake was monitored. Interestingly, the inhibitory effect of colchicine, cytochalasin D, phorbol 12-myristate 13-acetate, and chlorpromazine on endocytosis was highly correlated with thei