Dietary sulfate regulates the expression of the renal brush border Na/S(i) cotransporter NaS(i)-1

Abstract

Dietary inorganic sulfate (S(i)) intake is an important factor in the regulation of renal proximal tubular sodium-dependent S(i) transport (Na/S(i) cotransport). The purpose of the present study was to determine whether modulation of Na/S(i) cotransport activity by dietary S is mediated through regulation of the renal expression of the recently cloned NaS(i)-1 protein located in the apical brush border membrane (BBM) of the proximal tubule. It was found that rats fed a high S(i) diet had a marked increase in the renal excretion of S(i) and a concomitant decrease in BBM Na/S(i) cotransport activity when compared with rats on a control S(i) diet. The 43% decrease in BBM Na/S(i) cotransport activity was associated with a 33% decrease in BBM NaS(i)-1 protein abundance, as determined by Western blotting, and a 2.7- fold decrease in cortical NaS(i)-1 mRNA abundance, as determined by Northern blotting. Furthermore, cortical mRNA from rats fed a high S(i) diet when injected into Xenopus laevis oocytes led to a 2.2-fold decrease in Na/S(i) cotransport activity compared with mRNA isolated from control S(i) diet rats. This study indicates that adaptation to a high S(i) diet is accompanied by a decrease in renal cortical NaS(i)-1 mRNA abundance, which results in reduced expression of the NaS(i)- 1 protein at the level of the proximal tubular BBM.