engleski

Age-related expression of organic compound and water transporters in rat kidneys

Ageing is characterized by an impaired functional and structural integrity of mammalian kidneys. A diminished handling of organic compounds, drugs, and water, as observed in the kidneys of older humans and experimental animals, indicates that ageing may affect the expression and/or activity of the renal transporters that mediate excretion and/or reabsorption of organic anions and cations, glucose, and water. We compared the expression of relevant transporters in the kidneys of 3-month- old and 24-month-old male Wistar rats, including Na/K-ATPase, organic anion transporters Oat1 (Slc22a6), Oat2 (Slc22a7), Oat3 (Slc22a8), and Oat5 (Slc22a19), organic cation transporters Oct1 (Slc22a1) and Oct2 (Slc22a2), glucose transporters Sglt1 (Slc5a1) and Sglt2 (Slc5a2), and water channels AQP1 and AQP2. These transporters/channels reside in specific cell membrane domains along the nephron. Protein expression was studied by immunofluorescence cytochemistry (IC) in tissue cryosections and Western blotting (WB) in isolated membranes, whereas expression of mRNA in the tissue was tested by RT-PCR. The protein and mRNA expression of Oat1, Oat3, Oct1, Oct2, and AQP1 was significantly weaker in senescent animals. However, the expression of Na/K-ATPase, Oat2, Oat5, Sglt1, Sglt2, and AQP2 at both protein and/or mRNA levels was not affected by age. Our findings imply that the cellular uptake and excretion of endogenous and/or exogenous compounds in the kidneys can be compromised due to the ageing-related downregulation of certain renal transporters. This can lead to an impaired ability to maintain the homeostasis of specific compounds and an increased susceptibility to drug interaction and toxicity in kidneys and other organs.

aquaporins; membrane transporters; organic anions; organic cations; immunocytochemistry; mRNA expression; senescence; RT-PCR; Western blotting

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