engleski

Cadmium nephropathy is characterized by a selective loss of brush-border transporters

Chronic cadmium (Cd) intoxication in man and experimental animals is manifested by defects in reabsorption and secretion of various compounds in the renal proximal tubule (PT) (for literature see Herak-Kramberger et al.: Pfluegers Arch.-Eur. J. Physiol. 432:336-344, 1996). The mechanism of Cd action in PT cells is unclear. A possible target for Cd may be the activity or/and the abundance of various transporters and enzymes in the cell brush-border membrane (BBM). In an in vivo model of Cd-nephrotoxicity in rats, we used various biochemical and immunohistochemical techniques to study the activity and the expression of several BBM transporters and intracellular proteins. In comparison with the findings in control rats, Cd-intoxicated animals exhibited: a) a strongly diminished activity or/and expression of the sodium-glucose cotransporter, sodium-phosphate cotransporter type 2, and vacuolar H+-ATPase (V-ATPase) in BBM, b) an unchanged activity/expression of the sodium-sulphate cotransporter and water channel aquaporin-1 in BBM, c) a dramatically reduced endocytosis of the fluorescent dextrane in PT cells, and d) a marked depolymerisation of the cell microtubules. Cd also diminished acidification of intracellular vesicles in vitro by directly inhibiting the intrinsic V-ATPase activity and by increasing the proton conductance of the vesicle membrane. Thus, in PT cells, Cd may impair the microtubule- and V-ATPase-dependent recycling of BBM proteins via endo- and exocytosis. This may diminish endocytosis of the filtered proteins, causing proteinuria, and may selectively decrease abundance of the glucose and phosphate transporters in BBM, causing glucosuria and phosphaturia.

brush-border membrane; membrane transport; cadmium; nephrotoxicity; kidney; rat

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