engleski

Selective effects of cadmium upon plasma membrane proteins in rat proximal tubule

Cadmium (Cd) is a potent nephrotoxic heavy metal, which causes severe defects in reabsorption and secretion of various compounds in the mammalian proximal tubule (PT) (for literature see ref. (1)). The cellular mechanisms underlying Cd nephrotoxicity are not clear. Possible targets of Cd action at the cellular level could be plasma membrane transporters and enzymes in the PT cells, whose activity may be either directly inhibited by Cd or/and they may be reduced by number (1). It is generally assumed that Cd-nephropathy resembles the Fanconi syndrome, with an indiscriminative toxicity to all cellular functions. In order to investigate a possible specificity of Cd effects upon plasma membrane proteins in PT cells, by indirect immunofluorescence histochemistry (1, 2) we studied the expression of several proteins in the distinct cell membrane domains using 4 mm thick cryosections of the fixed kidney tissues from control rats and from rats subchronically intoxicated with Cd. Subchronic Cd nephropathy in rats was induced by injecting CdCl2 (2 mg Cd/kg body wt./day, s.c.) for 2 weeks. Immunostaining of cryosections with monoclonal or polyclonal antibodies to specific plasma membrane proteins revealed: a) the expression of Na/K-ATPase in the basolateral cell membrane was not significantly affected by Cd treatment, b) the expression of several brush-border proteins, including vacuolar H+-ATPase, sodium-phosphate cotransporter type II (NaPi-2), and dipeptidylpeptidase type IV (DPP IV), was dramatically reduced in Cd-intoxicated rats, and c) the expression of multidrug resistance P-glycoprotein (mdr1), a protein also located in the brush-border membrane, was strongly increased by Cd-treatment. Conclusion: in Cd nephrotoxicity the expression of various plasma membrane proteins seems to be selectively affected ; the abundance of a specific protein in the plasma membrane can be either unchanged or strongly diminished, or increased by Cd-treatment. The cause of this selectivity is unknown. References: 1. Herak-Kramberger M C, Spindler B, Biber J, Murer H, and Sabolic I, Pfluegers Arch. - Eur. J. Physiol. 432:336-344, 1996 2. Brown D, Lydon J, McLaughlin M, Stuart-Tilley A, Tyszkowski R, and Alper S., Histochem. Cell. Biol. 105:261-267, 1996

brush-border membrane; proximal tubule; cadmium; nephrotoxicity; kidney; rat

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