engleski

Gender differences in the renal expression of a sulfate anion transporter, sat-1, mediating sulfate-oxalate and sulfate-bicarbonate exchange

Objective: Most kidney stones consist of calcium oxalate and the prevalence to suffer from calcium oxalate urolithiasis is two times higher for men than for women. Oxalate is a metabolic end product and is excreted unchanged in the urine, either after absorption in the gastrointestinal tract or derived from endogenous metabolism of glycine, glycolate, hydroxyproline, and dietary Vitamin C. The aim of the present study was to determine the contribution of sat-1, a sulfate anion transporter, to the gender-dependent excretion of oxalate. Methods: Tracer uptake experiments were performed to functionally characterize sulfate and oxalate transport in sat-1-expressing oocytes and in renal proximal tubule basolateral membrane vesicles (BLMV) from male and female rats. The expression of sat-1 protein and its mRNA was evaluated in immunochemical and real-time RT-PCR studies in the kidney cortex of male (M) and female (F) rats. Results: In cis-inhibiton and trans-stimulation experiments, sat-1 was identified as a sulfate-oxalate/bicarbonate or oxalate-bicarbonate exchanger which works under physiological conditions (low plasma oxalate concentrations), as a sulfate-bicarbonate exchanger. Under increasing plasma oxalate concentrations, however, sat-1 preferentially mediates sulfate-oxalate exchange. In addition, sulfate uptake by sat-1 was competitively inhibited by thiosulfate and sulfite, but not by sulfide with Ki's of 101.7 +/- 9.7 and 53.8 +/- 10.9 &micro ; ; ; ; M, respectively. Preloading BLMVs from M rats with oxalate, resulted in an increased sulfate uptake as compared to BLMVs from F rats. Immunostaining of tissue cryosections, Western blotting of isolated BLMV, and real-time RT-PCR revealed a higher abundance of sat-1 protein and its mRNA in M kidney cortex. Conclusion: The M-dominat expression of sat-1 protein in the basolateral membrane of rat proximal tubule cells could explain, if similar gender differences are present in man, the higher prevalence of calcium oxalate stones observed in M gender. The recently reported reduced sulfotransferase isoenzyme activity and the reduced sulfate uptake in F BLMV may explain, at least in part, the observed gender differences in drug response.

Kidney; oxalate; sulfate; urolithiasis; gender differences

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