engleski

Mechanism of phosphaturia in cadmium-treated rats

MECHANISM OF PHOSPHATURIA IN CADMIUM-TREATED RATS C. M. Herak-Kramberger, I. Sabolic, Institute for Medical Research and Occupational Health, Zagreb, Croatia The kidney plays a central role in the homeostasis of inorganic phosphate (Pi).Pi filtered in glomeruli is reabsorbed up to 80% along the proximal tubule (PT) by the apically located sodium-dependent Pi transporter (NaPi). Cadmium (Cd) is a nephrotoxic agent which impairs the reabsorptive and secretory functions of PT cells, as manifested by phosphaturia, proteinuria, aminoaciduria, glucosuria and polyuria in man and experimental animals. The cellular mechanisms of Cd nephrotoxicity are poorly understood. In this study we investigated the effect of Cd on Pi transport in the PT at the cellular level. Wistar strain rats were treated with CdCl2 (2 mg Cd/kg B.W. s.c.) for 14 days. Compared to saline-treated control animals, the Cd-treated rats excreted significantly more urine, urinary protein and Pi, thus indicating a drastic impairment of Pi reabsorption in the PT. As studied by the rapid filtration technique in isolated renal cortical brush-border membrane vesicles (BBMV), the Na-gradient driven intravesicular uptake of radiolabeled phosphate and glucose was markedly decreased in Cd-treated animals. However, the uptake of radiolabeled sulfate in BBMV from Cd-treated rats was not different from controls. Western blotting (WB) of BBMV proteins and indirect immunocytochemistry in frozen sections of fixed kidneys, using an antibody against the NaPi-2, an isoform of the NaPi cotransporter present in the rat kidney brush-border membrane (BBM), showed a significantly reduced expression of this protein in Cd-treated rats. On the contrary, the WB labeling of water channel aquaporin 1 in BBMV from control and Cd-treated rats was similar. The northern blot analysis demonstrated that the expression of 2.7 kb NaPi-2-related mRNA was strongly reduced in Cd-affected kidneys. Our data indicate that (a) Cd reduces reabsorption of Pi in the PT by affecting the transcription-dependent expression of the functional NaPi cotransporter in the apical cell membrane, and (b) effects of Cd on BBM transporters are selective.

cadmium; phosphate transport; phosphaturia; kidney; rat

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