BMC Genomics Research article Expression profile of genes regulated by activity of the Na-H exchanger NHE1 Luanna K Putney1,2 and Diane L Barber*1 Address: 1Department of Stomatology, University of California San Francisco, San Francisco, CA 94143, USA and 2Office of Research Technology Transfer Center, University of California, Davis, Davis, CA 95616, USA Email: Luanna K Putney - lkputney@yahoo.com; Diane L Barber* - barber@itsa.ucsf.edu * Corresponding author BioMed Central Open Access Published: 16 July 2004 BMC Genomics 2004, 5:46 doi:10.1186/1471-2164-5-46 This article is available from: http://www.biomedcentral.com/1471-2164/5/46 Received: 24 March 2004 Accepted: 16 July 2004 © 2004 Putney and Barber; licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL. Abstract Background: In mammalian cells changes in intracellular pH (pHi), which are predominantly controlled by activity of plasma membrane ion exchangers, regulate a diverse range of normal and pathological cellular processes. How changes in pHi affect distinct cellular processes has primarily been determined by evaluating protein activities and we know little about how pHi regulates gene expression. Results: A global profile of genes regulated in mammalian fibroblasts by decreased pHi 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 pHi 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 pHi provides insight on candidate targets that might mediate established effects of pHi on a number of normal and pathological cell functions. Background Intracellular pH (pHi) homeostasis is exquisitely control- led. Variations in pHi both reflect and determine changes in a number of cellular processes, including adhesion, proliferation, metabolism, and programmed cell death. How pHi responds to and regulates distinct cellular proc- esses has primarily been determined by evaluating protein activities. Although effects of pHi on gene expression have been determined in yeast [1] and bacteria [2], we know lit- tle about how pHi regulates gene expression in metazoan cells. In metazoan cells pHi homeostasis is maintained by a number of H+ translocating mechanisms, primarily local- ized at the plasma membrane. In mammalian fibroblasts, a predominant regulator of pHi is the Na-H exchanger, NHE1. NHE1 is an H+ extruder, catalyzing an electroneu- tral exchange of extracellular Na+ for intracellular H+ and regulating pHi and cell volume homeostasis. NHE1 activ- ity is increased in response to growth factors and onco- genes [3,4], and increases in NHE1 activity and pHi promote cell cycle progression [5], increased proliferation [6,7], and cell survival [8]. NHE1 activity is necessary for a number of cytoskeleton-associated processes including cell shape determination [6], remodeling of cell-substrate Page 1 of 13 (page number not for citation purposes)