engleski

Expression of multidrug resistance P-glycoprotein Mdr1 (Abcb1) in rat kidney proximal tubules is up-regulated by nephrotoxic metals

Multidrug resistance P-glycoprotein Mdr1 (Abcb1), an ATP-driven efflux pump for potentially toxic metabolites and xenobiotics has been localized to the brush-border membrane of proximal tubule (PT) cells, where its expression may be affected by various stress-related factors, including heat-shock or cytotoxic metals. To test the effect of various metals upon renal Mdr1, we treated rats with 10 different metals for 2 weeks and compared the expression of Mdr1 protein in PT with the accumulation of these metals in the tissue. Whereas 6 of the tested metals (Cu, Mn, Zn, Ca, Mg, Al) showed a variable accumulation but no upregulation of Mdr1 expression, a metal compound cisPt and 3 well-known nephrotoxic metals (Pb, Cd, and Hg) exhibited strong accumulation in the cortical tissue and strong upregulation of transporter expression (3-, 6-, 15-, and 18-fold, respectively). The immunostaining experiments showed that Cd affected all PT segments in both cortex (including medullary rays) and outer stripe, whereas Hg, Pb, and cisPt predominantly affected the PT S3 segments in the medullary rays and outer stripe. The observed metal-induced increase in renal Mdr1 expression may be part of a specific cytoprotective response of PT cells to oxidative stress in order to remove peroxidized lipids, other toxic substances or metals, and to prevent an imminent cell death by apoptosis or necrosis.

cadmium, cisplatin, heavy metals, lead, mammalian kidney, mercury, nephrotoxicity

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