Gene Symbol: Slc9a1
Description: solute carrier family 9 (sodium/hydrogen exchanger), member 1
Alias: AW554487, Apnh, Mir5122, Nhe1, mir-5122, swe, sodium/hydrogen exchanger 1, NHE-1, Na(+)/H(+) exchanger 1, Na+/H+ antiporter, Na+/H+, amiloride sensitive, slow-wave epilepsy, solute carrier family 9, member 1
Species: mouse
Products:     Slc9a1

Top Publications

  1. Gonzalez Begne M, Nakamoto T, Nguyen H, Stewart A, Alper S, Melvin J. Enhanced formation of a HCO3- transport metabolon in exocrine cells of Nhe1-/- mice. J Biol Chem. 2007;282:35125-32 pubmed
    ..of this major Cl(-) uptake pathway on Na(+)/H(+) exchanger expression was examined in the parotid acinar cells of Nhe1(-/-) and Nhe2(-/-) mice, both of which exhibited impaired fluid secretion...
  2. Bachmann O, Riederer B, Rossmann H, Groos S, Schultheis P, Shull G, et al. The Na+/H+ exchanger isoform 2 is the predominant NHE isoform in murine colonic crypts and its lack causes NHE3 upregulation. Am J Physiol Gastrointest Liver Physiol. 2004;287:G125-33 pubmed
    ..To this end, we measured murine proximal colonic surface and crypt cell NHE1, NHE2, and NHE3 expression levels, transport rates in response to acid, hyperosmolarity and cAMP in murine proximal ..
  3. Kintner D, Su G, Lenart B, Ballard A, Meyer J, Ng L, et al. Increased tolerance to oxygen and glucose deprivation in astrocytes from Na(+)/H(+) exchanger isoform 1 null mice. Am J Physiol Cell Physiol. 2004;287:C12-21 pubmed
    The ubiquitously expressed Na(+)/H(+) exchanger isoform 1 (NHE1) functions as a major intracellular pH (pH(i)) regulatory mechanism in many cell types, and in some tissues its activity may contribute to ischemic injury...
  4. Good D, Watts B, George T, Meyer J, Shull G. Transepithelial HCO3- absorption is defective in renal thick ascending limbs from Na+/H+ exchanger NHE1 null mutant mice. Am J Physiol Renal Physiol. 2004;287:F1244-9 pubmed
    ..To assess the possible role of the Na(+)/H(+) exchanger NHE1 in this regulatory process, MTALs from wild-type and NHE1 knockout (NHE1(-/-)) mice were studied using in vitro ..
  5. Luo J, Chen H, Kintner D, Shull G, Sun D. Decreased neuronal death in Na+/H+ exchanger isoform 1-null mice after in vitro and in vivo ischemia. J Neurosci. 2005;25:11256-68 pubmed
    Na+/H+ exchanger isoform 1 (NHE1) is a major acid extrusion mechanism after intracellular acidosis. We hypothesized that stimulation of NHE1 after cerebral ischemia contributes to the disruption of Na+ homeostasis and neuronal death...
  6. Denker S, Huang D, Orlowski J, Furthmayr H, Barber D. Direct binding of the Na--H exchanger NHE1 to ERM proteins regulates the cortical cytoskeleton and cell shape independently of H(+) translocation. Mol Cell. 2000;6:1425-36 pubmed
    ..Here, we show that the plasma membrane ion exchanger NHE1 acts as an anchor for actin filaments to control the integrity of the cortical cytoskeleton...
  7. Denker S, Barber D. Cell migration requires both ion translocation and cytoskeletal anchoring by the Na-H exchanger NHE1. J Cell Biol. 2002;159:1087-96 pubmed
    ..We report that the Na-H exchanger isoform 1 (NHE1), a ubiquitously expressed plasma membrane ion exchanger, is necessary for establishing polarity in migrating ..
  8. Putney L, Barber D. Expression profile of genes regulated by activity of the Na-H exchanger NHE1. BMC Genomics. 2004;5:46 pubmed mammalian fibroblasts by decreased pHi induced by impaired activity of the plasma membrane Na-H exchanger NHE1 was characterized by using cDNA microarrays...
  9. Liu Y, Kintner D, Chanana V, Algharabli J, Chen X, Gao Y, et al. Activation of microglia depends on Na+/H+ exchange-mediated H+ homeostasis. J Neurosci. 2010;30:15210-20 pubmed publisher
    ..The study suggests that NHE-1 functions to maintain microglial pH(i) homeostasis allowing for sustained NADPH oxidase function and "respiratory" burst. ..

More Information


  1. McClive P, Morahan G. Assignment of the mouse homologues of 6 loci from HSA1p to chromosomes 3 and 4. Genomics. 1994;23:243-6 pubmed
    ..suggests that the human counterparts of these genes may have a similar order on human chromosome 1p and also indicates that Lap18, C1qB, and Nhe1 are candidates for a recently described diabetes susceptibility gene on mouse chromosome 4.
  2. Xue J, Mraiche F, Zhou D, Karmazyn M, Oka T, Fliegel L, et al. Elevated myocardial Na+/H+ exchanger isoform 1 activity elicits gene expression that leads to cardiac hypertrophy. Physiol Genomics. 2010;42:374-83 pubmed publisher
    In myocardial disease, elevated expression and activity of Na(+)/H(+) exchanger isoform 1 (NHE1) are detrimental. To better understand the involvement of NHE1, transgenic mice with elevated heart-specific NHE1 expression were studied...
  3. Zhao P, Ma M, Qian H, Xia Y. Down-regulation of delta-opioid receptors in Na+/H+ exchanger 1 null mutant mouse brain with epilepsy. Neurosci Res. 2005;53:442-6 pubmed
    Mice lacking Na+/H+ exchanger 1 (NHE1) show a unique epilepsy phenotype although the underlying mechanisms remain unclear...
  4. Zhou C, Baltz J. JAK2 mediates the acute response to decreased cell volume in mouse preimplantation embryos by activating NHE1. J Cell Physiol. 2013;228:428-38 pubmed publisher
    ..This activity was likely mediated by the NHE1 (Slc9a1) isoform, since it was blocked by the highly selective NHE1 inhibitor, cariporide, which also inhibited the ..
  5. Puranam R, McNamara J. Seizure disorders in mutant mice: relevance to human epilepsies. Curr Opin Neurobiol. 1999;9:281-7 pubmed
  6. Kumar A, Chang M, Fliegel L, Pervaiz S, Clement M. Oxidative repression of NHE1 gene expression involves iron-mediated caspase activity. Cell Death Differ. 2007;14:1733-46 pubmed
    The mechanism of Na(+)/H(+) exchanger 1 (NHE1) gene repression upon exposure of cells to non-apoptotic concentrations of hydrogen peroxide (H(2)O(2)) was investigated...
  7. Herron B, Liddell R, Parker A, Grant S, Kinne J, Fisher J, et al. A mutation in stratifin is responsible for the repeated epilation (Er) phenotype in mice. Nat Genet. 2005;37:1210-2 pubmed
    ..Er/+ mice expressed a truncated Sfn protein, which probably contributes to the defects in Er/Er and Er/+ epidermis and to cancer development in Er/+ mice. ..
  8. Lam T, Brennan Minnella A, Won S, Shen Y, Hefner C, Shi Y, et al. Intracellular pH reduction prevents excitotoxic and ischemic neuronal death by inhibiting NADPH oxidase. Proc Natl Acad Sci U S A. 2013;110:E4362-8 pubmed publisher
    ..was likewise prevented by inhibiting Na(+)/H(+) exchange and by reduced expression of the Na(+)/H(+) exchanger-1 (NHE1)...
  9. Zhou Y, Pasham V, Chatterjee S, Rotte A, Yang W, Bhandaru M, et al. Regulation of Na⁺/H⁺ Exchanger in Dendritic Cells by Akt1. Cell Physiol Biochem. 2015;36:1237-49 pubmed publisher
    ..The present observations demonstrate that Akt1 is required for the full stimulation of Na(+)/H(+) exchanger activity by LPS or oxidative stress in dendritic cells. ..
  10. Kilic A, Velic A, De Windt L, Fabritz L, Voss M, Mitko D, et al. Enhanced activity of the myocardial Na+/H+ exchanger NHE-1 contributes to cardiac remodeling in atrial natriuretic peptide receptor-deficient mice. Circulation. 2005;112:2307-17 pubmed
  11. Andersen A, Poulsen K, Lambert I, Pedersen S. HL-1 mouse cardiomyocyte injury and death after simulated ischemia and reperfusion: roles of pH, Ca2+-independent phospholipase A2, and Na+/H+ exchange. Am J Physiol Cell Physiol. 2009;296:C1227-42 pubmed publisher
    The Ca(2+)-independent phospholipase A(2) VI (iPLA(2)-VI) and the Na(+)/H(+) exchanger isoform 1 (NHE1) are highly pH-sensitive proteins that exert both protective and detrimental effects in cardiac ischemia-reperfusion...
  12. Odunewu Aderibigbe A, Fliegel L. Protein mediated regulation of the NHE1 isoform of the Na+/H+ exchanger in renal cells. A regulatory role of Hsp90 and AKT kinase. Cell Signal. 2017;36:145-153 pubmed publisher
    Na+/H+ exchanger isoform one (NHE1) is a pH regulatory protein that is present in renal tissues and serves to remove protons from within cells and protect against intracellular acidification...
  13. Guan Y, Dong J, Tackett L, Meyer J, Shull G, Montrose M. NHE2 is the main apical NHE in mouse colonic crypts but an alternative Na+-dependent acid extrusion mechanism is upregulated in NHE2-null mice. Am J Physiol Gastrointest Liver Physiol. 2006;291:G689-99 pubmed
    ..Transepithelial Na(+) leakage followed by activation of basolateral NHE1 could confound the outcomes; however, the rates of Na(+)-dependent pH(i) recovery were independent of ..
  14. Ferrazzano P, Shi Y, Manhas N, Wang Y, Hutchinson B, Chen X, et al. Inhibiting the Na+/H+ exchanger reduces reperfusion injury: a small animal MRI study. Front Biosci (Elite Ed). 2011;3:81-8 pubmed
    ..The results of this study demonstrate the therapeutic potential for inhibition of NHE-1 in treating cerebral ischemia. ..
  15. Shi Y, Yuan H, Kim D, Chanana V, Baba A, Matsuda T, et al. Stimulation of Na(+)/H(+) exchanger isoform 1 promotes microglial migration. PLoS ONE. 2013;8:e74201 pubmed publisher
    ..In addition, NHE-1 and NCXrev play a concerted role in BK-induced microglial migration via Na(+) and Ca(2+) signaling. ..
  16. Cox G, Lutz C, Yang C, Biemesderfer D, Bronson R, Fu A, et al. Sodium/hydrogen exchanger gene defect in slow-wave epilepsy mutant mice. Cell. 1997;91:139-48 pubmed
    The "housekeeping" sodium/hydrogen exchanger, NHE1, mediates the electroneutral 1:1 exchange of Na+ and H+ across the plasma membrane...
  17. Stiernet P, Nenquin M, Moulin P, Jonas J, Henquin J. Glucose-induced cytosolic pH changes in beta-cells and insulin secretion are not causally related: studies in islets lacking the Na+/H+ exchangeR NHE1. J Biol Chem. 2007;282:24538-46 pubmed Ca(2+) ([Ca(2+)](c)) and pH(c) in islets from normal mice and mice bearing an inactivating mutation of NHE1 (Slc9A1-swe/swe). The experiments were performed in HCO(-)(3)/CO(2) or HEPES/NaOH buffers...
  18. Vahle A, Domikowsky B, Schwöppe C, Krähling H, Mally S, Schäfers M, et al. Extracellular matrix composition and interstitial pH modulate NHE1-mediated melanoma cell motility. Int J Oncol. 2014;44:78-90 pubmed publisher
    The activity of the Na+/H+ exchanger NHE1 is required for human melanoma cell adhesion and migration. The goal of the present study was to suppress mouse melanoma (B16V) cell invasion in vivo by inhibiting NHE1...
  19. Jenkins E, Debnath S, Gundry S, Gundry S, Uyar U, Fata J. Intracellular pH regulation by Na?/H? exchanger-1 (NHE1) is required for growth factor-induced mammary branching morphogenesis. Dev Biol. 2012;365:71-81 pubmed publisher
    ..against cytosolic acidification is primarily a function of the ubiquitous plasma membrane Na+/H+exchanger-1 (NHE1), which uses a highly conserved process to transfer cytosolic hydrogen ions (H+) across plasma membranes in ..
  20. Clement D, Mally S, Stock C, Lethan M, Satir P, Schwab A, et al. PDGFR? signaling in the primary cilium regulates NHE1-dependent fibroblast migration via coordinated differential activity of MEK1/2-ERK1/2-p90RSK and AKT signaling pathways. J Cell Sci. 2013;126:953-65 pubmed publisher
    ..cascade through the PI3K-AKT and MEK1/2-ERK1/2 pathways leading to the activation of the Na(+)/H(+) exchanger, NHE1, cytoplasmic alkalinization and actin nucleation at the lamellipodium that supports directional cell migration...
  21. Brodnicki T, McClive P, Couper S, Morahan G. Localization of Idd11 using NOD congenic mouse strains: elimination of Slc9a1 as a candidate gene. Immunogenetics. 2000;51:37-41 pubmed
    ..The third NOD congenic strain, containing a B6 interval surrounding the Slc9a1 locus, was not protected against diabetes...
  22. Meisler M, Kearney J, Ottman R, Escayg A. Identification of epilepsy genes in human and mouse. Annu Rev Genet. 2001;35:567-88 pubmed
    ..The development of pharmaceuticals directed towards specific epilepsy genotypes can be anticipated, and the introduction of patient mutations into the mouse genome will provide models for testing these targeted therapies. ..
  23. Rorick N, Kinoshita A, Weirather J, Peyrard Janvid M, de Lima R, Dunnwald M, et al. Genomic strategy identifies a missense mutation in WD-repeat domain 65 (WDR65) in an individual with Van der Woude syndrome. Am J Med Genet A. 2011;155A:1314-21 pubmed publisher
    ..The expression and mutation data were consistent with the hypothesis that WDR65 was a novel gene involved in oral clefting. ..
  24. Rieder C, Fliegel L. Developmental regulation of Na(+)/H(+) exchanger expression in fetal and neonatal mice. Am J Physiol Heart Circ Physiol. 2002;283:H273-83 pubmed
    ..To examine transcriptional regulation of the NHE1 isoform of the Na(+)/H(+) exchanger, transgenic mice were created that contained the mouse NHE1 promoter driving ..
  25. Bhandaru M, Pasham V, Yang W, Bobbala D, Rotte A, Lang F. Effect of azathioprine on Na(+)/H(+) exchanger activity in dendritic cells. Cell Physiol Biochem. 2012;29:533-42 pubmed publisher
    ..In conclusion, azathioprine interferes with the activation of dendritic cell Na(+)/H(+) exchanger by bacterial lipopolysaccharides, an effect likely participating in the anti-inflammatory action of the drug. ..
  26. McClive P, Huang D, Morahan G. C57BL/6 and C57BL/10 inbred mouse strains differ at multiple loci on chromosome 4. Immunogenetics. 1994;39:286-8 pubmed
  27. Bell S, Schreiner C, Schultheis P, Miller M, Evans R, Vorhees C, et al. Targeted disruption of the murine Nhe1 locus induces ataxia, growth retardation, and seizures. Am J Physiol. 1999;276:C788-95 pubmed
    In most cells, the ubiquitously expressed Na+/H+ exchanger isoform 1 (NHE1) is thought to be a primary regulator of pH homeostasis, cell volume regulation, and the proliferative response to growth factor stimulation...
  28. Boedtkjer E, Damkier H, Aalkjaer C. NHE1 knockout reduces blood pressure and arterial media/lumen ratio with no effect on resting pH(i) in the vascular wall. J Physiol. 2012;590:1895-906 pubmed publisher
    ..Here, we investigated (a) implications of Na(+)/H(+) exchanger NHE1 knockout for vascular smooth muscle (VSMC) and endothelial cell (EC) pH(i) regulation, mesenteric artery morphology,..
  29. Nejsum L, Praetorius J, Nielsen S. NKCC1 and NHE1 are abundantly expressed in the basolateral plasma membrane of secretory coil cells in rat, mouse, and human sweat glands. Am J Physiol Cell Physiol. 2005;289:C333-40 pubmed
    ..Na(+)/H(+) exchanger (NHE) isoform 1 (NHE1) protein has been localized to both the duct and secretory coil of human sweat duct; however, the NHE1 abundance in ..
  30. Park K, Evans R, Watson G, Nehrke K, Richardson L, Bell S, et al. Defective fluid secretion and NaCl absorption in the parotid glands of Na+/H+ exchanger-deficient mice. J Biol Chem. 2001;276:27042-50 pubmed
    ..Mice with targeted disruptions of the Nhe1, Nhe2, and Nhe3 genes were used to study the in vivo functions of these exchangers in parotid glands...
  31. Praetorius J, Andreasen D, Jensen B, Ainsworth M, Friis U, Johansen T. NHE1, NHE2, and NHE3 contribute to regulation of intracellular pH in murine duodenal epithelial cells. Am J Physiol Gastrointest Liver Physiol. 2000;278:G197-206 pubmed
    ..b>NHE1, NHE2, and NHE3 were expressed at the mRNA level (RT-PCR) as well as at the protein level (Western blot analysis)...
  32. Siyanov V, Baltz J. NHE1 is the sodium-hydrogen exchanger active in acute intracellular pH regulation in preimplantation mouse embryos. Biol Reprod. 2013;88:157 pubmed publisher
    ..Of five plasma membrane NHE isoforms, mouse oocytes and preimplantation embryos express mRNAs encoding NHE1 (SLC9A1), NHE3 (SLC9A3), and NHE4 (SLC9A4), with higher mRNA levels for each in oocytes through one-cell stage embryos and ..
  33. Shimoda L, Fallon M, Pisarcik S, Wang J, Semenza G. HIF-1 regulates hypoxic induction of NHE1 expression and alkalinization of intracellular pH in pulmonary arterial myocytes. Am J Physiol Lung Cell Mol Physiol. 2006;291:L941-9 pubmed
    ..Consistent with previous results, increased NHE isoform 1 (NHE1) mRNA and protein, enhanced NHE activity, and an alkaline shift in pH(i) were observed in PASMCs isolated from wild-..
  34. Rotte A, Pasham V, Bhandaru M, Bobbala D, Zelenak C, Lang F. Rapamycin sensitive ROS formation and Na(+)/H(+) exchanger activity in dendritic cells. Cell Physiol Biochem. 2012;29:543-50 pubmed publisher
    ..In conclusion, in DCs rapamycin disrupts LPS induced ROS formation with subsequent inhibition of NHE activity, cell swelling and TNF-? release. ..
  35. Prasad V, Lorenz J, Miller M, Vairamani K, Nieman M, Wang Y, et al. Loss of NHE1 activity leads to reduced oxidative stress in heart and mitigates high-fat diet-induced myocardial stress. J Mol Cell Cardiol. 2013;65:33-42 pubmed publisher
    Acute inhibition of the NHE1 Na(+)/H(+) exchanger protects against ischemia-reperfusion injury and chronic inhibition attenuates development of cardiac hypertrophy and failure...
  36. Park J, Ryu J, Yun S, Kim M, Han H. Fibronectin stimulates migration through lipid raft dependent NHE-1 activation in mouse embryonic stem cells: involvement of RhoA, Ca(2+)/CaM, and ERK. Biochim Biophys Acta. 2012;1820:1618-27 pubmed publisher
    ..Thus, this study analyzed the relationship between FN and NHE in regulating the migration of mouse ESCs and their related signaling pathways. ..
  37. Hisamitsu T, Nakamura T, Wakabayashi S. Na(+)/H(+) exchanger 1 directly binds to calcineurin A and activates downstream NFAT signaling, leading to cardiomyocyte hypertrophy. Mol Cell Biol. 2012;32:3265-80 pubmed publisher
    ..The calcineurin A (CaNA) subunit was identified as a novel binding partner of plasma membrane Na(+)/H(+) exchanger 1 (NHE1). CaN is a Ca(2+)-dependent phosphatase involved in many cellular functions, including cardiac hypertrophy...
  38. Voelkl J, Lin Y, Alesutan I, Ahmed M, Pasham V, Mia S, et al. Sgk1 sensitivity of Na(+)/H(+) exchanger activity and cardiac remodeling following pressure overload. Basic Res Cardiol. 2012;107:236 pubmed publisher
    ..Compelling evidence points to a critical role of enhanced cardiac Na(+)/H(+) exchanger (NHE1) activity in the underlying pathophysiology...
  39. Szpirer C, Szpirer J, Riviere M, Levan G, Orlowski J. Chromosomal assignment of four genes encoding Na/H exchanger isoforms in human and rat. Mamm Genome. 1994;5:153-9 pubmed
    ..The rat Nhe1 gene was assigned to Chromosome (Chr)5, extending the homology with human chromosome 1p that has previously been ..
  40. Singh Y, Zhou Y, Zhang S, Abdelazeem K, Elvira B, Salker M, et al. Enhanced Reactive Oxygen Species Production, Acidic Cytosolic pH and Upregulated Na+/H+ Exchanger (NHE) in Dicer Deficient CD4+ T Cells. Cell Physiol Biochem. 2017;42:1377-1389 pubmed publisher
    ..T cells generate reactive oxygen species (ROS) with parallel H+ extrusion accomplished by the Na+/H+-exchanger 1 (NHE1)...
  41. Jenkins E, Debnath S, Varriano S, Gundry S, Fata J. Na(+) /H(+) exchanger 1 (NHE1) function is necessary for maintaining mammary tissue architecture. Dev Dyn. 2014;243:229-42 pubmed publisher
    ..Previously, we have shown that the Na(+) /H(+) exchanger 1 (NHE1), a critical regulator of intracellular pH, was necessary for mammary branching morphogenesis...
  42. Dudley C, Giuffra L, Tippett P, Kidd K, Reeders S. The Na+/H+ antiporter: a "melt" polymorphism allows regional mapping to the short arm of chromosome 1. Hum Genet. 1990;86:79-83 pubmed
    ..b>APNH, a gene encoding the antiporter, has been cloned and mapped to the short arm of chromosome 1 by in situ ..
  43. Li X, Misik A, Rieder C, Solaro R, Lowen A, Fliegel L. Thyroid hormone receptor alpha 1 regulates expression of the Na+/H+ exchanger (NHE1). J Biol Chem. 2002;277:28656-62 pubmed regulating expression of the Na+/H+ exchanger, we have characterized the regulation of a distal element of the NHE1 promoter by the thyroid hormone receptor...
  44. Nguyen H, Shull G, Melvin J. Muscarinic receptor-induced acidification in sublingual mucous acinar cells: loss of pH recovery in Na+-H+ exchanger-1 deficient mice. J Physiol. 2000;523 Pt 1:139-46 pubmed sublingual acinar cells, pH regulation was investigated in mice lacking Na+-H+ exchanger isoforms 1 and 2 (NHE1 and NHE2, respectively)...
  45. Ilic D, Mao Qiang M, Crumrine D, Dolganov G, Larocque N, Xu P, et al. Focal adhesion kinase controls pH-dependent epidermal barrier homeostasis by regulating actin-directed Na+/H+ exchanger 1 plasma membrane localization. Am J Pathol. 2007;170:2055-67 pubmed
    ..Thus, for plasma membrane localization in terminally differentiated keratinocytes, Na(+)/H(+) exchanger 1 requires an intact actin cytoskeleton, which is impaired in FAK-deficient cells. ..
  46. Morahan G, Rakar S. Localization of the mouse Na+/H+ exchanger gene on distal chromosome 4. Genomics. 1993;15:231-2 pubmed
    ..Comparison with previously reported strain distribution patterns shows that the gene encoding the mouse Na+/H+ exchanger maps to distal mouse Chromosome 4, between Lck and Akp-2. ..
  47. Pathak B, Shull G, Jenkins N, Copeland N. Mouse chromosomal location of four Na/H exchanger isoform genes. Genomics. 1996;31:261-3 pubmed
    The Na/H exchanger genes Slc9a1, Slc9a2, Slc9a3, and Slc9a4 have been mapped in the mouse using an interspecific backcross panel...
  48. Wang X, Yu M, Lam S, Leung K, Jiang J, Leung P, et al. Expression, immunolocalization, and functional activity of Na+/H+ exchanger isoforms in mouse endometrial epithelium. Biol Reprod. 2003;68:302-8 pubmed
    ..The presence of NHE1, NHE2, and NHE4, but not NHE3 mRNAs were revealed by RT-PCR...
  49. Yao H, Ma E, Gu X, Haddad G. Intracellular pH regulation of CA1 neurons in Na(+)/H(+) isoform 1 mutant mice. J Clin Invest. 1999;104:637-45 pubmed
    To understand the role of Na(+)/H(+) exchanger 1 (NHE1) in intracellular pH (pH(i)) regulation and neuronal function, we took advantage of natural knockout mice lacking NHE1, the most ubiquitously and densely expressed NHE isoform in the ..
  50. Orlowski J, Grinstein S. Na+/H+ exchangers of mammalian cells. J Biol Chem. 1997;272:22373-6 pubmed
  51. Wang H, Singh D, Yang W, Dyck J, Fliegel L. Structure and analysis of the mouse Na+/H+ exchanger (NHE1) gene: homology and conservation of splice sites. Mol Cell Biochem. 1996;165:155-9 pubmed
    ..We have cloned and analyzed the NHE1 isoform of the mouse genomic Na+/H+ exchanger...
  52. Xue J, Zhou D, Yao H, Haddad G. Role of transporters and ion channels in neuronal injury under hypoxia. Am J Physiol Regul Integr Comp Physiol. 2008;294:R451-7 pubmed
    ..cultured cortical neurons or hippocampal slices; 3) in contrast, inhibition of Na(+)/H(+) exchanger isoform 1 (NHE1) with either 10 microM HOE-642 or 2 microM T-162559 resulted in dramatic hypoxic injury (+95% for HOE-642 and +100% ..
  53. Singh Y, Zhou Y, Shi X, Zhang S, Umbach A, Salker M, et al. Alkaline Cytosolic pH and High Sodium Hydrogen Exchanger 1 (NHE1) Activity in Th9 Cells. J Biol Chem. 2016;291:23662-23671 pubmed
    ..The Na+/H+ exchanger 1 (NHE1; gene name Slc9?1)) is critically important for regulating intracellular pH (pHi), cell volume, ..
  54. Coaxum S, Garnovskaya M, Gooz M, Baldys A, Raymond J. Epidermal growth factor activates Na(+/)H(+) exchanger in podocytes through a mechanism that involves Janus kinase and calmodulin. Biochim Biophys Acta. 2009;1793:1174-81 pubmed publisher
  55. Wu K, Khan S, Lakhe Reddy S, Wang L, Jarad G, Miller R, et al. Renal tubular epithelial cell apoptosis is associated with caspase cleavage of the NHE1 Na+/H+ exchanger. Am J Physiol Renal Physiol. 2003;284:F829-39 pubmed
    ..We investigated whether RTC apoptosis requires caspase cleavage of NHE1. Staurosporine- and hypertonic NaCl-induced RTC apoptosis was associated with cell shrinkage and diminished ..
  56. Lee M, Ahn W, Choi J, Luo X, Seo J, Schultheis P, et al. Na(+)-dependent transporters mediate HCO(3)(-) salvage across the luminal membrane of the main pancreatic duct. J Clin Invest. 2000;105:1651-8 pubmed
    ..The pancreatic duct expresses NHE1 in the basolateral membrane, and NHE2 and NHE3 in the luminal membrane, but does not contain NHE4 or NHE5...
  57. Rieder C, Fliegel L. Transcriptional regulation of Na+/H+ exchanger expression in the intact mouse. Mol Cell Biochem. 2003;243:87-95 pubmed
    We examined regulation of the Na+/H+ exchanger (NHE1 isoform) in the developing mouse. We generated transgenic mice with the Na+/H+ exchanger promoter directing expression of the beta-Galactosidase reporter...
  58. Mo X, Wang L, Guo J, Hong W, Long S, Zhang L, et al. [Overexpression of NHE1 suppresses ABCA1 protein expression via increasing calpain activity in RAW264.7 cells]. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2017;33:12-16 pubmed
    Objective To investigate the effect of over-expressed Na+/H+ exchanger 1 (NHE1) on the protein expression of adenosine three phosphate binding cassette transporter A1 (ABCA1) in RAW264.7 cells. Methods RAW264...
  59. Boedtkjer E, Aalkjaer C. Insulin inhibits Na+/H+ exchange in vascular smooth muscle and endothelial cells in situ: involvement of H2O2 and tyrosine phosphatase SHP-2. Am J Physiol Heart Circ Physiol. 2009;296:H247-55 pubmed publisher
    ..H2O2 had no effect on Na+-HCO3- cotransport activity. NHE1 (slc9a1) was the only plasma membrane NHE isoform detected in mouse mesenteric arteries by RT-PCR analyses...
  60. Bonde L, Boedtkjer E. Extracellular acidosis and very low [Na+ ] inhibit NBCn1- and NHE1-mediated net acid extrusion from mouse vascular smooth muscle cells. Acta Physiol (Oxf). 2017;221:129-141 pubmed publisher
    The electroneutral Na+ , HCO3- cotransporter NBCn1 and Na+ /H+ exchanger NHE1 regulate acid-base balance in vascular smooth muscle cells (VSMCs) and modify artery function and structure...
  61. Feng Z, Tang L, Wu L, Cui S, Hong Q, Cai G, et al. Na+/H+ exchanger-1 reduces podocyte injury caused by endoplasmic reticulum stress via autophagy activation. Lab Invest. 2014;94:439-54 pubmed publisher
    ..This protective mechanism involves NHE-1 activation of autophagy via the PI3K/Akt pathway to reduce ER stress injury in podocytes. This mechanism may provide a new pathway to prevent podocyte injury. ..
  62. Li X, Karki P, Lei L, Wang H, Fliegel L. Na+/H+ exchanger isoform 1 facilitates cardiomyocyte embryonic stem cell differentiation. Am J Physiol Heart Circ Physiol. 2009;296:H159-70 pubmed publisher
    ..improving cardiomyocyte development from stem cells, we examined the role of the Na(+)/H(+) exchanger isoform 1 (NHE1) in cardiomyocyte differentiation...
  63. Wang P, Li L, Zhang Z, Kan Q, Gao F, Chen S. Time-dependent activity of Na+/H+ exchanger isoform 1 and homeostasis of intracellular pH in astrocytes exposed to CoCl2 treatment. Mol Med Rep. 2016;13:4443-50 pubmed publisher
    ..Na+/H+ exchanger isoform 1 (NHE1) is important in the mechanisms of hypoxia and intracellular pH (pHi) homeostasis...
  64. Gu X, Yao H, Haddad G. Increased neuronal excitability and seizures in the Na(+)/H(+) exchanger null mutant mouse. Am J Physiol Cell Physiol. 2001;281:C496-503 pubmed
    Mice lacking the Na(+)/H(+) exchanger isoform 1 (NHE1) manifest neurological diseases that include ataxia, motor deficits, and a seizure disorder...
  65. Maekawa N, Abe J, Shishido T, Itoh S, Ding B, Sharma V, et al. Inhibiting p90 ribosomal S6 kinase prevents (Na+)-H+ exchanger-mediated cardiac ischemia-reperfusion injury. Circulation. 2006;113:2516-23 pubmed
    Pharmacological and genetic studies indicate that the (Na+)-H+ exchanger isoform 1 (NHE1) plays a critical role in myocardial ischemia and reperfusion (I/R) injury...
  66. Zhou D, Xue J, Gavrialov O, Haddad G. Na+/H+ exchanger 1 deficiency alters gene expression in mouse brain. Physiol Genomics. 2004;18:331-9 pubmed
    Na(+)/H(+) exchanger 1 (NHE1) is well known to function as a major regulator of intracellular pH (pH(i)). It is activated by low pH(i) and exchanges extracellular Na(+) for intracellular H(+) to maintain cellular homeostasis...
  67. Behne M, Meyer J, Hanson K, Barry N, Murata S, Crumrine D, et al. NHE1 regulates the stratum corneum permeability barrier homeostasis. Microenvironment acidification assessed with fluorescence lifetime imaging. J Biol Chem. 2002;277:47399-406 pubmed
    ..b>NHE1 is the only Na(+)/H(+) antiporter isoform in keratinocytes and epidermis, and has been shown to regulate ..
  68. Zhou Y, Shi X, Chen H, Zhang S, Salker M, Mack A, et al. DJ-1/Park7 Sensitive Na+ /H+ Exchanger 1 (NHE1) in CD4+ T Cells. J Cell Physiol. 2017;232:3050-3059 pubmed publisher
    ..of reactive oxygen species (ROS) is paralleled by activation of the Na+ /H+ exchanger 1 (NHE1). ROS formation in CD4+ T cells plays a decisive role in regulating inflammatory responses...
  69. Barr K, Garrill A, Jones D, Orlowski J, Kidder G. Contributions of Na+/H+ exchanger isoforms to preimplantation development of the mouse. Mol Reprod Dev. 1998;50:146-53 pubmed
    ..We conclude that NHE-3, an oogenetic product that persists into the blastocyst stage, is the Na+/H+ exchanger isoform most likely to be involved in blastocoel expansion. ..
  70. Frankel W. Detecting genes in new and old mouse models for epilepsy: a prospectus through the magnifying glass. Epilepsy Res. 1999;36:97-110 pubmed
    ..with which this author has been fortunate enough to be intimately involved: slow-wave epilepsy (common gene symbol: swe, Chr 4); tottering (tg, Chr 8); and stargazer (stg, Chr 15)...
  71. Vanier H, Mraiche F, Li X, Fliegel L. Gender-specific effects of exercise on cardiac pathology in Na(+)/H(+) exchanger overexpressing mice. Mol Cell Biochem. 2012;368:103-10 pubmed publisher
    The Na(+)/H(+) exchanger isoform 1 (NHE1) has been implicated in various cardiac pathologies including ischemia/reperfusion damage to the myocardium and cardiac hypertrophy...
  72. Liu Y, Hitomi H, Diah S, Deguchi K, Mori H, Masaki T, et al. Roles of Na?/H? exchanger type 1 and intracellular pH in angiotensin II-induced reactive oxygen species generation and podocyte apoptosis. J Pharmacol Sci. 2013;122:176-83 pubmed
  73. Walker J, Undem C, Yun X, Lade J, Jiang H, Shimoda L. Role of Rho kinase and Na+/H+ exchange in hypoxia-induced pulmonary arterial smooth muscle cell proliferation and migration. Physiol Rep. 2016;4: pubmed publisher
    ..We previously demonstrated thatNHEisoform 1 (NHE1) is the predominant isoform expressed inPASMCs...
  74. Yun C, Tse C, Nath S, Levine S, Brant S, Donowitz M. Mammalian Na+/H+ exchanger gene family: structure and function studies. Am J Physiol. 1995;269:G1-11 pubmed
    ..of multiple forms of the exchangers was demonstrated by the recent cloning of four mammalian Na+/H+ exchangers, NHE1, NHE2, NHE3, and NHE4...
  75. Manhas N, Shi Y, Taunton J, Sun D. p90 activation contributes to cerebral ischemic damage via phosphorylation of Na+/H+ exchanger isoform 1. J Neurochem. 2010;114:1476-86 pubmed publisher
    ..Taken together, our study revealed that reperfusion triggers a transient stimulation of the ERK/p90(RSK) pathway. p90(RSK) activation contributes to cerebral ischemic damage in part via activation of NHE-1 protein. ..
  76. Damkier H, Prasad V, Hübner C, Praetorius J. Nhe1 is a luminal Na+/H+ exchanger in mouse choroid plexus and is targeted to the basolateral membrane in Ncbe/Nbcn2-null mice. Am J Physiol Cell Physiol. 2009;296:C1291-300 pubmed publisher
    ..Thus Ncbe/Nbcn2 mediates the DIDS-sensitive Na(+)-dependent pH(i) recovery in the CPE. The Na(+)/H(+) exchanger-1 Nhe1 is proposed to mediate similar functions as Ncbe/Nbcn2 in CPE...
  77. Yu L, Quinn D, Garg H, Hales C. Deficiency of the NHE1 gene prevents hypoxia-induced pulmonary hypertension and vascular remodeling. Am J Respir Crit Care Med. 2008;177:1276-84 pubmed publisher
    ..Other investigators recently observed increased expression of the NHE isoform 1 (NHE1) gene in rodents with pulmonary hypertension induced by hypoxia...
  78. Rocha M, Crockett D, Wong L, Richardson J, Sonsalla P. Na(+)/H(+) exchanger inhibition modifies dopamine neurotransmission during normal and metabolic stress conditions. J Neurochem. 2008;106:231-43 pubmed publisher
    ..The abundant NHE isoform 1 (NHE1) has also been linked to brain cell damage during metabolic stress...
  79. Brown D, Melvin J, Yule D. Critical role for NHE1 in intracellular pH regulation in pancreatic acinar cells. Am J Physiol Gastrointest Liver Physiol. 2003;285:G804-12 pubmed
    ..The targeted disruption of the Nhe1 gene also completely abolished pHi recovery from an acid load in pancreatic acini in both HCO3--containing and HCO3-..
  80. Ouyang Q, Lizarraga S, Schmidt M, Yang U, Gong J, Ellisor D, et al. Christianson syndrome protein NHE6 modulates TrkB endosomal signaling required for neuronal circuit development. Neuron. 2013;80:97-112 pubmed publisher
    ..Finally, exogenous BDNF rescues defects in neuronal arborization. We propose that NHE6 mutation leads to circuit defects that are in part due to impoverished neuronal arborization that may be treatable by enhanced TrkB signaling. ..
  81. Kao L, Kurtz L, Shao X, Papadopoulos M, Liu L, Bok D, et al. Severe neurologic impairment in mice with targeted disruption of the electrogenic sodium bicarbonate cotransporter NBCe2 (Slc4a5 gene). J Biol Chem. 2011;286:32563-74 pubmed publisher
    ..Our findings are the first demonstration of the fundamental importance of NBCe2 in the biology of the nervous system. ..
  82. Schneider L, Stock C, Dieterich P, Jensen B, Pedersen L, Satir P, et al. The Na+/H+ exchanger NHE1 is required for directional migration stimulated via PDGFR-alpha in the primary cilium. J Cell Biol. 2009;185:163-76 pubmed publisher
    ..In this study, we investigate the functional relationship between ciliary PDGFR-alpha and the Na(+)/H(+) exchanger NHE1 in directional cell migration...
  83. Morahan G, McClive P, Huang D, Little P, Baxter A. Genetic and physiological association of diabetes susceptibility with raised Na+/H+ exchange activity. Proc Natl Acad Sci U S A. 1994;91:5898-902 pubmed
    ..These results implicate the Na+/H+ exchanger (antiporter) in the development of type 1 diabetes and may provide a screening test for at-risk individuals as well as offering prospects for disease prevention. ..
  84. Xue L, Aihara E, Wang T, Montrose M. Trefoil factor 2 requires Na/H exchanger 2 activity to enhance mouse gastric epithelial repair. J Biol Chem. 2011;286:38375-82 pubmed publisher (luminal 10 ?m 5-(N-ethyl-N-isopropyl) amiloride or 25 ?m HOE694) slows restitution 72-83% in wild-type or NHE1(-/-) mice...
  85. Anzawa R, Seki S, Nagoshi T, Taniguchi I, Feuvray D, Yoshimura M. The role of Na+/H+ exchanger in Ca2+ overload and ischemic myocardial damage in hearts from type 2 diabetic db/db mice. Cardiovasc Diabetol. 2012;11:33 pubmed publisher
    ..NHE plays a key role in enhancing cytoplasmic Ca(2+) overload during ischemia-reperfusion and severely impairing post-ischemic cardiac function in hearts from type 2 diabetic db/db mice. ..