engleski

EXPRESSION OF RENAL ORGANIC ANION TRANSPORTERS Oat1 AND Oat3, BUT NOT Na/K-ATPase, IS DOWNREGULATED IN OLD MALE RATS

In the process of elimination of endogenous and xenobiotic organic anions (OA) from the body via the renal tubules, the basolateral (BL) Na/K-ATPase generates ionic gradients necessary to drive the cellular uptake of OA from the peritubular space by Na+-dicarboxylate co-transporter NaDC-3 (Slc13a3) and OA transporters (exchangers) Oat1 (Slc22a6) and Oat3 (Slc22a8). In the mammalian kidney, aging is characterized by impairment of the structure, function and regulatory mechanisms. Aging may affect the expression and/or activity of renal Oats responsible for elimination of endogenous metabolites and pharmacokinetics of commonly used drugs and other xenobiotics. The expression of renal Oats in old humans or experimental animals has not been reported. In this study we evaluated the expression of Na/K-ATPase, Oat1 and Oat3 proteins in 3 months (young) and 2 years old (old) male Wistar rats by immunocytochemistry in tissue cryosections and by Western blotting (WB) of total cell membranes (TCM) isolated from the whole kidneys. In young rats, the BL staining intensity of Oat1 was strong in the PT convoluted (S2) and weak in the PT straight (S3) segments. In old rats, the staining intensity of Oat1 was reduced in both segments, largely in BL invaginations (BLI). In WB, the abundance of Oat1 protein in TCM was diminished in old animals. The BL-localized Oat3 in young rats was stained strongly in various cortical tubules, and weakly in S3 and collecting ducts. In old rats, the staining intensity of Oat3 in all tubules was strongly reduced, mainly in BLI. WB exhibited weaker Oat3 protein bands in TCM from old rats. In contrast to Oats, the expression of Na/K-ATPase in young and old rats showed no difference in the staining pattern along the nephron and abundance of protein in TCM, and no loss of BLI in old animals. In conclusion, aging in rats is associated with a selective loss of Oat1 and Oat3 proteins from BLI in the renal tubules.

aging; basolateral membrane; drug transporters; kidney; nephron

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