engleski

Nephrotoxic heavy metals increase expression of mdr1 in rat kideny cortex brush-border membrane

NEPHROTOXIC HEAVY METALS INCREASE EXPRESSION OF MDR1 IN RAT KIDNEY CORTEX BRUSH-BORDER MEMBRANE Herak-Kramberger CM*, Blanusa M*, Milkovic-Kraus S*, Thevenod F*, and Sabolic I* (introduced by D. Brown), IMI, Zagreb, Croatia & II. Physiology, University of Saarland, Homburg/Saar, Germany The multidrug resistance P-glycoprotein (mdr1), an efflux pump for various xenobiotics, is expressed on the apical membrane of excretory epitelial cells, including the kidney proximal tubule (PT). The physiological role of mdr1 in PT is not known. Mdr1 expression in cells may be affected by environmental stress and cytotoxic heavy metals (Chin et al., J. Biol. Chem, 265:221-226, 1990). Using an anti-mdr1 antibody (C219), we studied mdr1 expression in PT by immunohistochemistry and in isolated renal cortical brush-border membranes (BBM) by western blotting in control rats and in rats treated in vivo with various metals for 5 (cis-Pt) or 14 days (Pb, Hg, Cd, Cu, Zn, Mn, Ca, Mg, Al, La). The amount of mdr1 in BBM was correlated to the metal concentration in the renal cortical tissue measured by atomic absorption spectrometry. In control rats, a very low tissue concentration of the metals and a heterogeneous expression of mdr1 in BBM along the PT (S1<S2<S3) was detected. In experimental rats, concentration of all metals in the tissue increased between 7- (Mn) and 3000-fold (Cd). Only cis-Pt, Pb, Cd and Hg increased mdr1 expression in BBM by 3-, 6-, 15-, and 18-fold, respectively. Conclusion: a) nephrotoxic heavy metals increase mdr1 expression in the rat kidney BBM in vivo, b) this increase may be part of a specific cytoprotective response of PT cells to oxidative stress induced by nephrotoxic heavy metals.

multidrug resistance; mdr1; heavy metals; kidney; rat

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