Expression profile of genes regulated by activity of the Na-H exchanger NHE1

Background: In mammalian cells changes in intracellular pH (pH(i)), which are predominantly controlled by activity of plasma membrane ion exchangers, regulate a diverse range of normal and pathological cellular processes. How changes in pH(i) affect distinct cellular processes has primarily been determined by evaluating protein activities and we know little about how pH(i) regulates gene expression. Results: A global profile of genes regulated in mammalian fibroblasts by decreased pH(i) induced by impaired activity of the plasma membrane Na-H exchanger NHE1 was characterized by using cDNA microarrays. Analysis of selected genes by quantitative RT-PCR, TaqMan, and immunoblot analyses confirmed results obtained from cDNA arrays. Consistent with established roles of pH(i) and NHE1 activity in cell proliferation and oncogenic transformation, grouping regulated genes into functional categories and biological pathways indicated a predominant number of genes with altered expression were associated with growth factor signaling, oncogenesis, and cell cycle progression. Conclusion: A comprehensive analysis of genes selectively regulated by pH(i) provides insight on candidate targets that might mediate established effects of pH(i) on a number of normal and pathological cell functions.