engleski

The expression of multidrug resistence P-glycoprotein (mdr1) increases along kidney proximal tubule (PT), and its distribution inverses in cadmium (Cd)-intoxicated rats

THE EXPRESSION OF MULTIDRUG RESISTANCE P-GLYCOPROTEIN (mdr1) INCREASES ALONG KIDNEY PROXIMAL TUBULE (PT), AND ITS DISTRIBUTION INVERSES IN CADMIUM (Cd)-INTOXICATED RATS. F. Thevenod, C. Heark-Kramberger & I. Sabolic. II Physiologisches Institut, Univ. Saarland, Homburg, Germany & IMI, Zagreb, Croatia. Mdr1 is an ATP-dependent transporter expressed in the brush-border membrane (BBM) of kidney (PT), where it contributes to the excretion of toxic organic compounds. We have investigated the distribution of mdr1 protein along the PT in control and cadmium Cd-intoxicated rats. Cd-intoxication was induced by daily injections of 2 mg Cd/kg b.w., s.c., for up to 14 days. Mdr1 expression in renal tissue was determined with the anti-mdr1 monoclonal antibody C219 by Western blot analysis of BBM from superficial cortex (SC) and outer stripe (OS) and by indirect immunofluorescence in frozen kidney sections. In controls, immunofluorescence staining of brush-border (BB) in proximal convoluted tubules (PCT) was weak (S1<S2), whereas staining of BB in proximal straight tubules (PST) was strong. Western blot of BBM from OS revealed a 2-fold higher amount of mdr1 compared to BBM from SC. Following Cd injections for 12-14 days, the amount of mdr1 in BBM from SC increased significantly. In BBM from OS, however, after 10-14 days of Cd-treatment, mdr1 expression decreased 4-fold. Similarly, immunofluorescence showed increased staining of BB in PCT, whereas staining of BB in PST was weak. The data show that a) expression of the mdr1 protein in BBM along the segments (S1-S3) of PT in controls follows the sequence S1<S2<S3, and b) in Cd-intoxication, mdr1 expression in S1 and S2 PT segments is upregulated and downregulated in the S3 segment, thus indicating different control mechanisms of mdr1 expression in the initial (S1 and S2) and terminal (S3) segments of the PT.

multidrug resistence; proximal tubule; cadmium; rat

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