Regulation of Na+/H+ exchanger-NHE3 by angiotensin-II in OKP cells

Liping Xu, Mehul P. Dixit, Kevin D. Nullmeyer, Hua Xu, Pawel R. Kiela, Ronald M. Lynch, Fayez K. Ghishan

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

Previous studies have shown that circulating Angiotensin II (A-II) increases renal Na+ reabsorption via elevated Na+/H+ exchanger isoform 3 (NHE3) activity. We hypothesized that prolonged exposure to A-II leads to an increased expression of renal NHE3 by a transcriptionally mediated mechanism. To test this hypothesis, we utilized the proximal tubule-like OKP cell line to evaluate the effects of 16-h treatment with A-II on NHE3 activity and gene expression. A-II significantly stimulated NHE3-mediated, S-3226-sensitive Na+/H+ exchange. Inhibition of transcription with actinomycin D abolished the stimulatory effect of A-II on NHE3-mediated pH recovery in acid-loaded OKP cells. This prolonged exposure to A-II was also found to elevate endogenous NHE3 mRNA (by 40%)-an effect also abolished by inhibition of gene transcription. To evaluate the molecular mechanism by which A-II regulates NHE3 expression, the activity of NHE3 promoter driven reporter gene was analyzed in transient transfection assays. In transfected OKP cells, rat NHE3 promoter activity was significantly stimulated by A-II treatment, and preliminary mapping indicated that the A-II responsive element(s) is present between 149 and 548 bp upstream of the transcription initiation site in the NHE3 gene promoter. We conclude that a transcriptional mechanism is at least partially responsible for the chronic effects of A-II treatment on renal NHE3 activity.

Original languageEnglish (US)
Pages (from-to)519-526
Number of pages8
JournalBiochimica et Biophysica Acta - Biomembranes
Volume1758
Issue number4
DOIs
StatePublished - Apr 1 2006

Keywords

  • Activity
  • Antiport
  • Kidney
  • Promoter
  • Proximal tubule
  • Slc9A3

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Cell Biology

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