Decreased NHE8 isoform expression and defective acidification in proximal convoluted tubules of senile rats

Abstract

We have previously found that aged rats show decreased proximal acidification without changes in NHE3 or V-H + ATPase expression in brush border membrane vesicles. However, we did not identify any mechanism underlying these observations. The aim of the present work was to evaluate some of the regulatory systems of proximal acidification that could be affected by aging. We measured plasma concentrations of parathyroid hormone (PTH) and the amount of cAMP in the renal cortex of young and old Wistar rats. PTH plasma concentration was increased in old rats, whereas, although it showed a tendency to increase, the cAMP content in the renal cortex of old rats was not significantly different compared with the cortex of young rats. We measured the abundance of NHE8 isoforms of the Na + /H + exchanger in brush border membrane vesicles from proximal convoluted tubules (PCT) of young and old rats by western blot analysis. We performed RT-PCR experiments in renal cortex homogenates from both experimental groups to evaluate mRNA expression of NHE3, NHE8 and H + ATPase. In senile rats, we detected a decreased abundance (at both gene expression and protein level) of the NHE8 isoform.These results could explain previous observations in which proximal tubule acidification appears affected in aged rats through a decrease in the activity of ethylisopropyl amiloride (EIPA)-and Bafilomycinsensitive components, without changes in the NHE3 and V-H + ATPase abundance in the apical membrane of the PCT.

SLC9/NHE gene family, a plasma membrane and organellar family of Na+/H+ exchangers

“…Decreased expression of NHE8 protein and message is associated with defective acidification in proximal convoluted tubules of aged rats (Fiori et al, 2009). In intestinal inflammation, both NHE3 and NHE8 are decreased, accounting for reduction of Na absorption in inflammatory diarrhea.…”

The regulation of proximal tubular salt transport in hypertension: an update

“…NHE1 is present in the basolateral membrane of most segments of the renal tubule. NHE8 is expressed in the apical membrane of renal proximal tubules in neonates [25] and aged rats [26 • ] and has a similar function to NHE3 [26 • ,27]. However, it is mostly intracellular in adults [28 • ].…”

The Role of Plasma Membrane Sodium/Hydrogen Exchangers in Gastrointestinal Functions: Proliferation and Differentiation, Fluid/Electrolyte Transport and Barrier Integrity

“…NHE8 expression in the intestine is age dependent, with the highest expression in young animals ( Xu et al, 2005 ; Xu et al, 2008 ; Fiori et al, 2009 ; Xu et al, 2012 ). Several studies have shown that the binding of the Sp3 transcriptional factor to the NHE8 basal promoter is crucial for the transcriptional regulation of NHE8 ( Xu et al, 2009 ; Xu et al, 2010a ; Xu H. et al, 2015 ).…”