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


CONCLUSIONS
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.
Putney
Luanna K
LK
Department of Stomatology, University of California San Francisco, San Francisco, CA 94143, USA. lkputney@yahoo.com
Barber
Diane L
DL
D019943:Amino Acid Substitution; D000818:Animals; D027682:Cation Transport Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D002453:Cell Cycle / Q000235:genetics; D002455:Cell Division / Q000235:genetics; D002460:Cell Line / Q000166:cytology / Q000378:metabolism; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D004734:Energy Metabolism / Q000235:genetics; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006133:Growth Substances / Q000502:physiology; D006863:Hydrogen-Ion Concentration; D017136:Ion Transport / Q000235:genetics; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008870:Microtubules / Q000378:metabolism; D020125:Mutation, Missense; D020411:Oligonucleotide Array Sequence Analysis; D017354:Point Mutation; D011522:Protons; D012333:RNA, Messenger / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D000074082:Sodium-Hydrogen Exchanger 1; D017923:Sodium-Hydrogen Exchangers / Q000235:genetics / Q000502:physiology*
D027682:Cation Transport Proteins; D018076:DNA, Complementary; D006133:Growth Substances; D008565:Membrane Proteins; D011522:Protons; D012333:RNA, Messenger; C490997:Slc9a1 protein, mouse; D000074082:Sodium-Hydrogen Exchanger 1; D017923:Sodium-Hydrogen Exchangers