engleski

Mechanism of proteinuria in cadmium-intoxicated rats

MECHANISM OF PROTEINURIA IN CADMIUM-INTOXICATED RATS Sabolic I., C. M. Herak-Kramberger, and D. Brown, IMI, Zagreb, Croatia, and Renal Unit, MGH, Boston, USA. Cadmium (Cd)-intoxicated rats exhibit a marked polyuria, phosphaturia, and proteinuria. We have investigated cellular causes of the Cd-induced proteinuria. Following perfusion with the FITC-dextran in vivo, the Cd-treated rats (2 mg Cd/kg B.W., s.c. for 14 days) exhibited (i) a strongly diminished uptake of this fluid-phase marker into renal proximal tubule cells (PTC) and (ii) randomly scattered endosomes in the cell cytoplasm, thus indicating an impaired vesicle trafficking via endo- and exocytosis. Cd may affect endocytosis by inhibiting the V-type H+-ATPase in the cell organelles; the immunohistochemical studies in frozen sections of the fixed kidney cortex and the Western blot studies in brush-border membrane vesicles from the renal cortex showed a strong decrease of the 31 kD and 70 kD H+-ATPase subunits antigenicity in samples from Cd-treated rats. As measured by the Pi liberation assay, the bafilomycin sensitive ATPase in the PTC brush-border membrane was drastically inhibited by Cd in vivo and in vitro. In addition, the acridine orange fluorescence quench experiments in isolated renal cortical endocytic vesicles revealed that Cd dissipated the transmembrane DpH by increasing H+ conductance of the vesicle membrane. We conclude that proteinuria in Cd-intoxicated rats may result from a limited endocytosis of the filtered proteins due to impaired acidification mechanisms in the PTC organelles.

proteinuria; vacuolar ATPase; endocytosis; cadmium; kidney; rat

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