SCNN1A

Summary

Gene Symbol: SCNN1A
Description: sodium channel epithelial 1 alpha subunit
Alias: BESC2, ENaCa, ENaCalpha, SCNEA, SCNN1, amiloride-sensitive sodium channel subunit alpha, alpha ENaC-2, alpha-ENaC, alpha-NaCH, amiloride-sensitive epithelial sodium channel alpha subunit, amiloride-sensitive sodium channel subunit alpha 2, epithelial Na(+) channel subunit alpha, nasal epithelial sodium channel alpha subunit, nonvoltage-gated sodium channel 1 subunit alpha, sodium channel, non voltage gated 1 alpha subunit, sodium channel, non-voltage-gated 1 alpha, sodium channel, nonvoltage-gated 1 alpha
Species: human
Products:     SCNN1A

Top Publications

  1. Chang S, Grunder S, Hanukoglu A, Rosler A, Mathew P, Hanukoglu I, et al. Mutations in subunits of the epithelial sodium channel cause salt wasting with hyperkalaemic acidosis, pseudohypoaldosteronism type 1. Nat Genet. 1996;12:248-53 pubmed
    ..These findings demonstrate the molecular basis and explain the pathophysiology of this disease. ..
  2. Schaedel C, Marthinsen L, Kristoffersson A, Kornfält R, Nilsson K, Orlenius B, et al. Lung symptoms in pseudohypoaldosteronism type 1 are associated with deficiency of the alpha-subunit of the epithelial sodium channel. J Pediatr. 1999;135:739-45 pubmed
    ..To study patients with autosomal recessive pseudohypoaldosteronism type 1 and to relate pulmonary disease to gene mutations of the epithelial sodium channel (ENaC)...
  3. Mick V, Itani O, Loftus R, Husted R, Schmidt T, Thomas C. The alpha-subunit of the epithelial sodium channel is an aldosterone-induced transcript in mammalian collecting ducts, and this transcriptional response is mediated via distinct cis-elements in the 5'-flanking region of the gene. Mol Endocrinol. 2001;15:575-88 pubmed
    ..Systemic administration of aldosterone increases alpha ENaC mRNA expression in mammalian kidney, suggesting that the alpha ENaC gene is a target for aldosterone action in ..
  4. Donaldson S, Hirsh A, Li D, Holloway G, Chao J, Boucher R, et al. Regulation of the epithelial sodium channel by serine proteases in human airways. J Biol Chem. 2002;277:8338-45 pubmed
    ..These data, therefore, suggest that protease-mediated regulation of sodium absorption is a function of human airway epithelia, and prostasin is a likely candidate for this activity. ..
  5. Fronius M, Bogdan R, Althaus M, Morty R, Clauss W. Epithelial Na+ channels derived from human lung are activated by shear force. Respir Physiol Neurobiol. 2010;170:113-9 pubmed publisher
    ..From our observations we conclude that lung-derived hENaCs are directly activated by SF and this may represent an important feature for the regulation of pulmonary Na(+) reabsorption and pulmonary fluid homeostasis. ..
  6. MYERBURG M, Harvey P, Heidrich E, Pilewski J, Butterworth M. Acute regulation of the epithelial sodium channel in airway epithelia by proteases and trafficking. Am J Respir Cell Mol Biol. 2010;43:712-9 pubmed publisher
    ..These findings demonstrate that Na(+) absorption in the airway is acutely modulated by the coordinated trafficking of channels to the luminal surface and by the proteolytic activation of ENaC in response to ASL volume expansion. ..
  7. Snyder P, Olson D, Kabra R, Zhou R, Steines J. cAMP and serum and glucocorticoid-inducible kinase (SGK) regulate the epithelial Na(+) channel through convergent phosphorylation of Nedd4-2. J Biol Chem. 2004;279:45753-8 pubmed
    ..The data suggest that cAMP regulates ENaC in part by phosphorylation and inhibition of Nedd4-2. Moreover, Nedd4-2 is a central convergence point for kinase regulation of Na(+) transport. ..
  8. Richard K, Ramminger S, Forsyth L, Burchell A, Wilson S. Thyroid hormone potentiates glucocorticoid-evoked airway Na+ transport without affecting alpha-ENaC transcription. FEBS Lett. 2004;576:339-42 pubmed
    ..The facilitation of Na+ transport may thus reflect control over events downstream to transcription. ..
  9. Edelheit O, Hanukoglu I, Gizewska M, Kandemir N, Tenenbaum Rakover Y, Yurdakok M, et al. Novel mutations in epithelial sodium channel (ENaC) subunit genes and phenotypic expression of multisystem pseudohypoaldosteronism. Clin Endocrinol (Oxf). 2005;62:547-53 pubmed
    ..In this study we examined three PHA patients to identify mutations responsible for PHA with different clinical presentations...

More Information

Publications154 found, 100 shown here

  1. Woollhead A, Baines D. Forskolin-induced cell shrinkage and apical translocation of functional enhanced green fluorescent protein-human alphaENaC in H441 lung epithelial cell monolayers. J Biol Chem. 2006;281:5158-68 pubmed
  2. Dirlewanger M, Huser D, Zennaro M, Girardin E, Schild L, Schwitzgebel V. A homozygous missense mutation in SCNN1A is responsible for a transient neonatal form of pseudohypoaldosteronism type 1. Am J Physiol Endocrinol Metab. 2011;301:E467-73 pubmed publisher
    ..We identified a homozygous missense mutation in the SCNN1A gene (c.727T>C/p...
  3. Ruan Y, Guo J, Liu X, Zhang R, Tsang L, Dong J, et al. Activation of the epithelial Na+ channel triggers prostaglandin E? release and production required for embryo implantation. Nat Med. 2012;18:1112-7 pubmed publisher
    ..These results indicate a previously undefined role of ENaC in regulating the PGE? production and release required for embryo implantation, defects that may be a cause of miscarriage and low success rates in IVF. ..
  4. Vormfelde S, Sehrt D, Toliat M, Schirmer M, Meineke I, Tzvetkov M, et al. Genetic variation in the renal sodium transporters NKCC2, NCC, and ENaC in relation to the effects of loop diuretic drugs. Clin Pharmacol Ther. 2007;82:300-9 pubmed
    ..in the renal sodium transporters NKCC2 (coded by SLC12A1), NCC (SLC12A3), and ENaC (three subunits coded by SCNN1A, SCNN1B, and SCNN1G)...
  5. Raikwar N, Thomas C. Nedd4-2 isoforms ubiquitinate individual epithelial sodium channel subunits and reduce surface expression and function of the epithelial sodium channel. Am J Physiol Renal Physiol. 2008;294:F1157-65 pubmed publisher
    ..Inhibitors of the proteasome increase ubiquitination of ENaC subunits and stimulate Na(+) transport in M-1 cells consistent with a role for the ubiquitin-proteasome pathway in regulating Na(+) transport in the collecting duct. ..
  6. Zhou M, Fu J, Huang W, Shen L, Xiao L, Song Y, et al. Increased cystic fibrosis transmembrane conductance regulators expression and decreased epithelial sodium channel alpha subunits expression in early abortion: findings from a mouse model and clinical cases of abortion. PLoS ONE. 2014;9:e99521 pubmed publisher
    ..In conclusion, increased CFTR expression and decreased ENaC-α expression in the decidua of early abortion may relate with failure of early pregnancy. ..
  7. McGillick E, Orgeig S, Morrison J. Regulation of lung maturation by prolyl hydroxylase domain inhibition in the lung of the normally grown and placentally restricted fetus in late gestation. Am J Physiol Regul Integr Comp Physiol. 2016;310:R1226-43 pubmed publisher
    ..of genes regulating hypoxia signaling (HIF-3α, ACE1), antioxidant defense (CAT), lung liquid reabsorption (SCNN1-A, ATP1-A1, AQP-1, AQP-5), and surfactant maturation (SFTP-A, SFTP-B, SFTP-C, PCYT1A, LPCAT, ABCA3, LAMP3) in ..
  8. Saxena S, Quick M, Tousson A, Oh Y, Warnock D. Interaction of syntaxins with the amiloride-sensitive epithelial sodium channel. J Biol Chem. 1999;274:20812-7 pubmed
  9. Boulkroun S, Ruffieux Daidié D, Vitagliano J, Poirot O, Charles R, Lagnaz D, et al. Vasopressin-inducible ubiquitin-specific protease 10 increases ENaC cell surface expression by deubiquitylating and stabilizing sorting nexin 3. Am J Physiol Renal Physiol. 2008;295:F889-900 pubmed publisher
    ..In mCCD(cl1) cells, vasopressin increases SNX3 protein but not mRNA, supporting the idea that the vasopressin-induced Usp10 deubiquitylates and stabilizes endogenous SNX3 and consequently promotes cell surface expression of ENaC. ..
  10. Kapoor N, Bartoszewski R, Qadri Y, Bebok Z, Bubien J, Fuller C, et al. Knockdown of ASIC1 and epithelial sodium channel subunits inhibits glioblastoma whole cell current and cell migration. J Biol Chem. 2009;284:24526-41 pubmed publisher
    ..We also found a significant inhibition of D54-MG cell migration after ASIC1, alphaENaC, or gammaENaC knockdown, consistent with the hypothesis that ENaC/Degenerin subunits play an important role in glioma cell biology. ..
  11. Dolan S, Hollegaard M, Merialdi M, Betran A, Allen T, Abelow C, et al. Synopsis of preterm birth genetic association studies: the preterm birth genetics knowledge base (PTBGene). Public Health Genomics. 2010;13:514-23 pubmed publisher
  12. Marino G, Kotsias B. Expression of the epithelial sodium channel sensitive to amiloride (ENaC) in normal and preeclamptic human placenta. Placenta. 2013;34:197-200 pubmed publisher
    ..Although the role of ENaC in placental tissues is poorly understood, these differences may have consequences for the ion transport involved in the pathophysiology of preeclampsia. ..
  13. Arai K, Zachman K, Shibasaki T, Chrousos G. Polymorphisms of amiloride-sensitive sodium channel subunits in five sporadic cases of pseudohypoaldosteronism: do they have pathologic potential?. J Clin Endocrinol Metab. 1999;84:2434-7 pubmed
    ..The latter would be compatible with a sporadic presentation and digenic or multigenic expression and heredity in PHA...
  14. Malbert Colas L, Nicolas G, Galand C, Lecomte M, Dhermy D. Identification of new partners of the epithelial sodium channel alpha subunit. C R Biol. 2003;326:615-24 pubmed
    ..All these partners are implicated in protein trafficking and could be involved in the regulation of ENaC activity. ..
  15. Rauh R, Dinudom A, Fotia A, Paulides M, Kumar S, Korbmacher C, et al. Stimulation of the epithelial sodium channel (ENaC) by the serum- and glucocorticoid-inducible kinase (Sgk) involves the PY motifs of the channel but is independent of sodium feedback inhibition. Pflugers Arch. 2006;452:290-9 pubmed
    ..We conclude that the stimulatory effect of Sgk on ENaC requires the presence of the channel's PY motifs, but it is not due to the interruption of Na+ feedback regulation. ..
  16. Hu J, Bengrine A, Lis A, Awayda M. Alternative mechanism of activation of the epithelial na+ channel by cleavage. J Biol Chem. 2009;284:36334-45 pubmed publisher
    ..1 microS), and were insensitive to subtilisin. Collectively, these data support an alternative hypothesis of ENaC activation by cleavage that may involve the loss of the first transmembrane domain from the channel complex. ..
  17. Sun X, Ruan Y, Guo J, Chen H, Tsang L, Zhang X, et al. Regulation of miR-101/miR-199a-3p by the epithelial sodium channel during embryo implantation: involvement of CREB phosphorylation. Reproduction. 2014;148:559-68 pubmed publisher
    ..These results reveal a novel molecular mechanism modulating COX2 expression during embryo implantation via ENaC-dependent CREB activation and COX2-targeting miRNAs. ..
  18. Koch S, Macinnis M, Rupert J, Sporer B, Koehle M. Pharmacogenetic Effects of Inhaled Salbutamol on 10-km Time Trial Performance in Competitive Male and Female Cyclists. Clin J Sport Med. 2016;26:145-51 pubmed publisher
    ..SNPs) in the adrenergic β2-receptor gene (ADRB2, rs1042713, and rs1042714) and epithelial Na channel gene (SCNN1A, rs2228576) on cycling performance after the inhalation of salbutamol...
  19. Yang Y, Kim J, Kwock C. Association of Genetic Variation in the Epithelial Sodium Channel Gene with Urinary Sodium Excretion and Blood Pressure. Nutrients. 2018;10: pubmed publisher
    ..0. Thirty-four single nucleotide polymorphisms (SNPs) were extracted for gene regions (SCNN1A, SCNN1B, and SCNN1G) as additive components by using Plink...
  20. Hong G, Lockhart A, Davis B, Rahmoune H, Baker S, Ye L, et al. PPARgamma activation enhances cell surface ENaCalpha via up-regulation of SGK1 in human collecting duct cells. FASEB J. 2003;17:1966-8 pubmed
    ..by pretreatment with a specific PPARgamma antagonist, and that this leads to increased levels of cell surface ENaCalpha. Electrophoretic mobility shift assays suggest that these effects are caused by binding of PPARgamma to a ..
  21. Kong X, Ma H, Li H, Xiong C. Blockade of epithelial sodium channels improves sperm motility in asthenospermia patients. Int J Androl. 2009;32:330-6 pubmed publisher
    ..89% from 9.50 +/- 6.11% to 20.51 +/- 12.13% (mean +/- SEM, p < 0.001). The improved sperm motility by EIPA has important clinical implications in the treatment of asthenospermia and certainly warrants further investigation. ..
  22. Edinger R, Lebowitz J, Li H, Alzamora R, Wang H, Johnson J, et al. Functional regulation of the epithelial Na+ channel by IkappaB kinase-beta occurs via phosphorylation of the ubiquitin ligase Nedd4-2. J Biol Chem. 2009;284:150-7 pubmed publisher
    ..In summary, these results suggest a novel mode of ENaC regulation that occurs through IKKbeta-dependent Nedd4-2 phosphorylation at a recognized SGK1 and protein kinase A target site. ..
  23. Buck T, Plavchak L, Roy A, Donnelly B, Kashlan O, Kleyman T, et al. The Lhs1/GRP170 chaperones facilitate the endoplasmic reticulum-associated degradation of the epithelial sodium channel. J Biol Chem. 2013;288:18366-80 pubmed publisher
    ..These data establish the first evidence that Lhs1/Grp170 chaperones can act as mediators of ERAD substrate selection. ..
  24. Wang H, Traub L, Weixel K, Hawryluk M, Shah N, Edinger R, et al. Clathrin-mediated endocytosis of the epithelial sodium channel. Role of epsin. J Biol Chem. 2006;281:14129-35 pubmed
    ..These results identify epsin as an accessory protein linking ENaC to the clathrin-based endocytic machinery thereby regulating the activity of this ion channel at the cell surface. ..
  25. Rauh R, Diakov A, Tzschoppe A, Korbmacher J, Azad A, Cuppens H, et al. A mutation of the epithelial sodium channel associated with atypical cystic fibrosis increases channel open probability and reduces Na+ self inhibition. J Physiol. 2010;588:1211-25 pubmed publisher
    ..The resulting gain-of-function phenotype of the mutant channel might contribute to the pathophysiology of CF in patients carrying this mutation. ..
  26. Faria D, Lentze N, Almaca J, Luz S, Alessio L, Tian Y, et al. Regulation of ENaC biogenesis by the stress response protein SERP1. Pflugers Arch. 2012;463:819-27 pubmed publisher
    ..In contrast to the inhibitory effects on ENaC, SERP1 appears to promote expression of CFTR. Taken together, SERP1 is a novel cochaperone and regulator of ENaC expression. ..
  27. Staub O, Gautschi I, Ishikawa T, Breitschopf K, Ciechanover A, Schild L, et al. Regulation of stability and function of the epithelial Na+ channel (ENaC) by ubiquitination. EMBO J. 1997;16:6325-36 pubmed
    ..of ubiquitination and increased channel activity, an effect augmented by N-terminal Lys to Arg mutations in alpha ENaC, but not in beta ENaC...
  28. McDonald F, Western A, McNeil J, Thomas B, Olson D, Snyder P. Ubiquitin-protein ligase WWP2 binds to and downregulates the epithelial Na(+) channel. Am J Physiol Renal Physiol. 2002;283:F431-6 pubmed
    ..Thus expression, binding, and functional data all suggest that WWP2 is a candidate to regulate ENaC-mediated Na(+) transport in epithelia. ..
  29. Yan W, Spruce L, Rosenblatt M, Kleyman T, Rubenstein R. Intracellular trafficking of a polymorphism in the COOH terminus of the alpha-subunit of the human epithelial sodium channel is modulated by casein kinase 1. Am J Physiol Renal Physiol. 2007;293:F868-76 pubmed
  30. Marunaka Y. Characteristics and pharmacological regulation of epithelial Na+ channel (ENaC) and epithelial Na+ transport. J Pharmacol Sci. 2014;126:21-36 pubmed
    ..In the present review article, I discuss the characteristics of ENaC and how these factors are regulated. ..
  31. Bangel N, Dahlhoff C, Sobczak K, Weber W, Kusche Vihrog K. Upregulated expression of ENaC in human CF nasal epithelium. J Cyst Fibros. 2008;7:197-205 pubmed
    ..We conclude that the Na+ hyperabsorption in CF is not caused by mutations in hnENaC, but by an increase in the transcription of the hnENaC subunits. This could be induced by a disturbed regulation of the channel in CF. ..
  32. Kim S, Park H, Choi H, Chung H, Choi J. Functional and molecular expression of epithelial sodium channels in cultured human endolymphatic sac epithelial cells. Otol Neurotol. 2009;30:529-34 pubmed publisher
    ..Epithelial sodium channels are expressed in cultured human endolymphatic sac (ES) epithelial (HESE) cells and epithelial sodium channel (ENaC) expression is suppressed by interleukin 1beta...
  33. Azad A, Rauh R, Vermeulen F, Jaspers M, Korbmacher J, Boissier B, et al. Mutations in the amiloride-sensitive epithelial sodium channel in patients with cystic fibrosis-like disease. Hum Mutat. 2009;30:1093-103 pubmed publisher
    ..V114I and p.F61L in SCNN1A. More importantly, a more than three-fold significant increase in incidence of several rare ENaC polymorphisms was ..
  34. Song W, Wei S, Zhou Y, Lazrak A, Liu G, Londino J, et al. Inhibition of lung fluid clearance and epithelial Na+ channels by chlorine, hypochlorous acid, and chloramines. J Biol Chem. 2010;285:9716-28 pubmed publisher
    ..We concluded that HOCl and its reactive intermediates (such as organic chloramines) inhibit ENaC by affecting channel gating, which could be relieved by proteases cleavage. ..
  35. Amazit L, Le Billan F, Kolkhof P, Lamribet K, Viengchareun S, Fay M, et al. Finerenone Impedes Aldosterone-dependent Nuclear Import of the Mineralocorticoid Receptor and Prevents Genomic Recruitment of Steroid Receptor Coactivator-1. J Biol Chem. 2015;290:21876-89 pubmed publisher
    ..inhibits MR, steroid receptor coactivator-1, and RNA polymerase II binding at the regulatory sequence of the SCNN1A gene and also remarkably reduces basal MR and steroid receptor coactivator-1 recruitment, unraveling a specific ..
  36. Xu D, Wang H, You G. An Essential Role of Nedd4-2 in the Ubiquitination, Expression, and Function of Organic Anion Transporter-3. Mol Pharm. 2016;13:621-30 pubmed publisher
    ..In conclusion, our results provided the first evidence that Nedd4-2 is an important regulator for OAT3 ubiquitination, expression, and transport activity. ..
  37. Salih M, Gautschi I, van Bemmelen M, Di Benedetto M, Brooks A, Lugtenberg D, et al. A Missense Mutation in the Extracellular Domain of αENaC Causes Liddle Syndrome. J Am Soc Nephrol. 2017;28:3291-3299 pubmed publisher
    ..This mutation may explain other cases of patients with resistant hypertension and also provides novel insight into ENaC activation, which is relevant for kidney sodium reabsorption and salt-sensitive hypertension. ..
  38. Egli M, Duplain H, Lepori M, Cook S, Nicod P, Hummler E, et al. Defective respiratory amiloride-sensitive sodium transport predisposes to pulmonary oedema and delays its resolution in mice. J Physiol. 2004;560:857-65 pubmed
    ..These data in mice strengthen indirect evidence provided by clinical studies, suggesting that defective respiratory transepithelial sodium transport may also facilitate pulmonary oedema in humans. ..
  39. Xu W, Hong S, Zeitchek M, Cooper G, Jia S, Xie P, et al. Hydration status regulates sodium flux and inflammatory pathways through epithelial sodium channel (ENaC) in the skin. J Invest Dermatol. 2015;135:796-806 pubmed publisher
    ..Our results indicate that ENaC responds to small changes in sodium concentration with inflammatory mediators and suggest that the ENaC pathway is a potential target for a strategy to prevent fibrosis. ..
  40. Harvey K, Dinudom A, Komwatana P, Jolliffe C, Day M, Parasivam G, et al. All three WW domains of murine Nedd4 are involved in the regulation of epithelial sodium channels by intracellular Na+. J Biol Chem. 1999;274:12525-30 pubmed
    ..We propose that Nedd4-mediated down-regulation of Na+ channels involves the binding of WW domains 2 and 3 to the Na+ channel and of WW domain 1 to an unknown associated protein. ..
  41. Condliffe S, Carattino M, Frizzell R, Zhang H. Syntaxin 1A regulates ENaC via domain-specific interactions. J Biol Chem. 2003;278:12796-804 pubmed
    ..This study provides support for the concept that S1A inhibits ENaC-mediated Na(+) transport by decreasing cell surface channel number via direct protein-protein interactions at the ENaC C termini. ..
  42. Shimizu N, Yoshikawa N, Wada T, Handa H, Sano M, Fukuda K, et al. Tissue- and context-dependent modulation of hormonal sensitivity of glucocorticoid-responsive genes by hexamethylene bisacetamide-inducible protein 1. Mol Endocrinol. 2008;22:2609-23 pubmed publisher
    ..We here addressed this issue using atp1a1 and scnn1a, both of which are up-regulated in response to corticosteroids in human embryonic kidney-derived 293 cells, but ..
  43. Rollins B, Garcia Caballero A, Stutts M, Tarran R. SPLUNC1 expression reduces surface levels of the epithelial sodium channel (ENaC) in Xenopus laevis oocytes. Channels (Austin). 2010;4:255-9 pubmed
    ..A better understanding of ENaC's regulation by endogenous inhibitors may aid in the development of novel therapies designed to inhibit hyperactive ENaC in cystic fibrosis epithelia. ..
  44. Hanukoglu I, Boggula V, Vaknine H, Sharma S, KLEYMAN T, Hanukoglu A. Expression of epithelial sodium channel (ENaC) and CFTR in the human epidermis and epidermal appendages. Histochem Cell Biol. 2017;147:733-748 pubmed publisher
    ..PHA patients may develop folliculitis, miliaria rubra, and atopic dermatitis-like skin lesions, due to sweat gland duct occlusion and inflammation of eccrine glands as a result of salt accumulation. ..
  45. Mutesa L, Azad A, Verhaeghe C, Segers K, Vanbellinghen J, Ngendahayo L, et al. Genetic analysis of Rwandan patients with cystic fibrosis-like symptoms: identification of novel cystic fibrosis transmembrane conductance regulator and epithelial sodium channel gene variants. Chest. 2009;135:1233-1242 pubmed publisher
    ..liquid chromatography followed by direct sequencing; whereas, the sodium channel non-voltage-gated 1 alpha (SCNN1A), sodium channel non-voltage-gated 1 beta (SCNN1B), and sodium channel non-voltage-gated 1 gamma (SCNN1G) subunits ..
  46. Handschick M, Hedtfeld S, Tummler B. Frequency of the hyperactive W493R ENaC variant in carriers of a CFTR mutation. J Cyst Fibros. 2012;11:53-5 pubmed publisher
    ..CF-like disease has been reported in a heterozygous carrier of F508del CFTR and the hyperactive variant p.W493R-SCNN1A of the epithelial sodium channel (ENaC). The hypothesis that heterozygosity for p...
  47. Oliynyk I, Hussain R, Amin A, Johannesson M, Roomans G. The effect of NO-donors on chloride efflux, intracellular Ca(2+) concentration and mRNA expression of CFTR and ENaC in cystic fibrosis airway epithelial cells. Exp Mol Pathol. 2013;94:474-80 pubmed publisher
    ..It can be concluded that the effect of GSNO on Cl(-) efflux is, at least in part, due to its properties as an NO-donor, and the effect is likely to be mediated by CFTR, not by Ca(2+)-activated Cl(-) channels. ..
  48. Boggula V, Hanukoglu I, Sagiv R, Enuka Y, Hanukoglu A. Expression of the epithelial sodium channel (ENaC) in the endometrium - Implications for fertility in a patient with pseudohypoaldosteronism. J Steroid Biochem Mol Biol. 2018;183:137-141 pubmed publisher
    ..form of this disease results from mutations in the genes that encode for the epithelial sodium channel subunits, SCNN1A, SCNN1B, and SCNN1G. A PHA patient under our care failed to conceive after many years and IVF trials...
  49. Wang X, Lu X, Lin R, Wang S, Zhang L, Qian J, et al. Lack of association of functional variants in alpha-ENaC gene and essential hypertension in two ethnic groups in China. Kidney Blood Press Res. 2008;31:268-73 pubmed publisher
    ..For the above variants, we did not confirm the hypothesis that subtle genetic changes in alpha-ENaC subunits might be at the origin of essential hypertension in our populations. ..
  50. Garcia Caballero A, Rasmussen J, Gaillard E, Watson M, Olsen J, Donaldson S, et al. SPLUNC1 regulates airway surface liquid volume by protecting ENaC from proteolytic cleavage. Proc Natl Acad Sci U S A. 2009;106:11412-7 pubmed publisher
    ..Thus, we propose that SPLUNC1 is secreted onto mucosal surfaces as a soluble volume sensor whose concentration and dilution can regulate ENaC activity and mucosal volumes, including that of airway surface liquid. ..
  51. Mueller G, Yan W, Copelovitch L, Jarman S, Wang Z, Kinlough C, et al. Multiple residues in the distal C terminus of the ?-subunit have roles in modulating human epithelial sodium channel activity. Am J Physiol Renal Physiol. 2012;303:F220-8 pubmed publisher
    ..Our results suggest that multiple residues in the distal part of the cytoplasmic C terminus have roles in modulating channel activity. ..
  52. Yang X, He J, Gu D, Hixson J, Huang J, Rao D, et al. Associations of epithelial sodium channel genes with blood pressure changes and hypertension incidence: the GenSalt study. Am J Hypertens. 2014;27:1370-6 pubmed publisher
    ..b>SCNN1A SNP rs11064153 and SCNN1G SNP rs4401050 were significantly associated with longitudinal changes in SBP after ..
  53. Boiko N, Kucher V, Stockand J. Pseudohypoaldosteronism type 1 and Liddle's syndrome mutations that affect the single-channel properties of the epithelial Na+ channel. Physiol Rep. 2015;3: pubmed publisher
    These studies test whether three disease-causing mutations in genes (SCNN1A and SCNN1G) encoding subunits of the epithelial Na(+) channel, ENaC, affect the biophysical and gating properties of this important renal ion channel...
  54. Wang J, Yu T, Yin L, Li J, Yu L, Shen Y, et al. Novel mutations in the SCNN1A gene causing Pseudohypoaldosteronism type 1. PLoS ONE. 2013;8:e65676 pubmed publisher
    ..Mutations in the subunit genes (SCNN1A, SCNN1B, SCNN1G) of the epithelial sodium channel (ENaC) and the NR3C2 gene encoding the mineralocorticoid ..
  55. Foxx Lupo W, Wheatley C, Baker S, Cassuto N, Delamere N, Snyder E. Genetic variation of the alpha subunit of the epithelial Na+ channel influences exhaled Na+ in healthy humans. Respir Physiol Neurobiol. 2011;179:205-11 pubmed publisher
    ..05). The results are consistent with the notion that genetic variation of ENaC influences ?(2)-adrenergic receptor stimulated Na(+) clearance in the lungs, as there was a significant reduction in exhaled Na(+) over time in the AA group. ..
  56. Enuka Y, Hanukoglu I, Edelheit O, Vaknine H, Hanukoglu A. Epithelial sodium channels (ENaC) are uniformly distributed on motile cilia in the oviduct and the respiratory airways. Histochem Cell Biol. 2012;137:339-53 pubmed publisher
    ..ENaC on motile cilia should be essential for diverse functions of motile cilia, such as germ cell transport, fertilization, implantation, clearance of respiratory airways and cell migration. ..
  57. Kim J, Kwon H, Jang Y. Effects of rhinovirus infection on the expression and function of cystic fibrosis transmembrane conductance regulator and epithelial sodium channel in human nasal mucosa. Ann Allergy Asthma Immunol. 2012;108:182-7 pubmed publisher
    ..In contrast, ENaC expression and function were increased by RV infection. Therefore, RV infection may impair mucociliary transport of nasal epithelium by these alterations. ..
  58. Chandrashekar J, Kuhn C, Oka Y, Yarmolinsky D, Hummler E, Ryba N, et al. The cells and peripheral representation of sodium taste in mice. Nature. 2010;464:297-301 pubmed publisher
    ..We genetically engineered mice lacking ENaCalpha in TRCs, and produced animals exhibiting a complete loss of salt attraction and sodium taste responses...
  59. Hobbs C, Blanchard M, Alijevic O, Tan C, Kellenberger S, Bencharit S, et al. Identification of the SPLUNC1 ENaC-inhibitory domain yields novel strategies to treat sodium hyperabsorption in cystic fibrosis airway epithelial cultures. Am J Physiol Lung Cell Mol Physiol. 2013;305:L990-L1001 pubmed publisher
    ..Furthermore, the robust inhibition of ENaC by the S18 peptide suggests that this peptide may be suitable for treating CF lung disease. ..
  60. Straniero L, Soldà G, Costantino L, Seia M, Melotti P, Colombo C, et al. Whole-gene CFTR sequencing combined with digital RT-PCR improves genetic diagnosis of cystic fibrosis. J Hum Genet. 2016;61:977-984 pubmed publisher
    ..We also included in the custom NGS design the coding portions of the SCNN1A, SCNN1B and SCNN1G genes, encoding the subunits of the sodium channel ENaC, which were found to be mutated in CF-..
  61. Meisler M, Barrow L, Canessa C, Rossier B. SCNN1, an epithelial cell sodium channel gene in the conserved linkage group on mouse chromosome 6 and human chromosome 12. Genomics. 1994;24:185-6 pubmed
    b>SCNN1, a gene encoding a nonvoltage-gated sodium channel, was detected using a rat colon cDNA probe with homology to Caenorhabditis elegans degenerin genes. Human SCNN1 was assigned to chromosome 12 using the NIGMS hybrid mapping panel 2...
  62. Zhou R, Kabra R, Olson D, Piper R, Snyder P. Hrs controls sorting of the epithelial Na+ channel between endosomal degradation and recycling pathways. J Biol Chem. 2010;285:30523-30 pubmed publisher
    ..In contrast, Hrs-?UIM had no effect on degradation of uncleaved inactive channels. The data support a model in which Nedd4-2 induces binding of ENaC to Hrs, which mediates the sorting decision between ENaC degradation and recycling. ..
  63. Janér C, Pitkänen O, Helve O, Andersson S. Airway expression of the epithelial sodium channel ?-subunit correlates with cortisol in term newborns. Pediatrics. 2011;128:e414-21 pubmed publisher
    ..These results support a role in humans for endogenous glucocorticoids in the regulation of airway ion transport. This finding may be a physiologic mechanism mediating pulmonary adaptation in the newborn infant. ..
  64. Zhao C, Crosby J, Lv T, Bai D, Monia B, Guo S. Antisense oligonucleotide targeting of mRNAs encoding ENaC subunits ?, ?, and ? improves cystic fibrosis-like disease in mice. J Cyst Fibros. 2018;: pubmed publisher
    The epithelial sodium channel ENaC consists of three subunits encoded by Scnn1a, Scnn1b, and Scnn1g and increased sodium absorption through this channel is hypothesized to lead to mucus dehydration and accumulation in cystic fibrosis (CF) ..
  65. Saxena A, Hanukoglu I, Saxena D, Thompson R, Gardiner R, Hanukoglu A. Novel mutations responsible for autosomal recessive multisystem pseudohypoaldosteronism and sequence variants in epithelial sodium channel alpha-, beta-, and gamma-subunit genes. J Clin Endocrinol Metab. 2002;87:3344-50 pubmed
    ..Our analyses revealed the following homozygous mutations in three probands: 1) insertion of a T in exon 8 of the alpha ENaC gene that causes a frameshift error at Tyr(447) and leads to a premature stop codon at K459 in a Pakistani ..
  66. Zeissig S, Bergann T, Fromm A, Bojarski C, Heller F, Guenther U, et al. Altered ENaC expression leads to impaired sodium absorption in the noninflamed intestine in Crohn's disease. Gastroenterology. 2008;134:1436-47 pubmed publisher
    ..In CD, macroscopically noninflamed colon contributes to diarrhea via impaired ENaC-mediated sodium absorption. Inhibition of extracellular signal-regulated kinase might serve as a potential therapeutic strategy for CD diarrhea. ..
  67. Collier D, Snyder P. Extracellular protons regulate human ENaC by modulating Na+ self-inhibition. J Biol Chem. 2009;284:792-8 pubmed publisher
    ..Together, the data support a model in which protons modulate ENaC gating by relieving Na(+) self-inhibition. We speculate that this may be an important mechanism to facilitate epithelial Na(+) transport under conditions of acidosis. ..
  68. He M, Liu S, Gallolu Kankanamalage S, Borromeo M, Girard L, Gazdar A, et al. The Epithelial Sodium Channel (?ENaC) Is a Downstream Therapeutic Target of ASCL1 in Pulmonary Neuroendocrine Tumors. Transl Oncol. 2018;11:292-299 pubmed publisher
    ..From this analysis, we discovered that the gene SCNN1A, which encodes the alpha subunit of the epithelial sodium channel (?ENaC), is highly correlated with ASCL1 ..
  69. Tucker J, Tamba K, Lee Y, Shen L, Warnock D, Oh Y. Cloning and functional studies of splice variants of the alpha-subunit of the amiloride-sensitive Na+ channel. Am J Physiol. 1998;274:C1081-9 pubmed
    The alpha-subunit of the amiloride-sensitive epithelial Na+ channel (alpha ENaC) is critical in forming an ion conductive pore in the membrane...
  70. Kashlan O, Maarouf A, Kussius C, Denshaw R, Blumenthal K, Kleyman T. Distinct structural elements in the first membrane-spanning segment of the epithelial sodium channel. J Biol Chem. 2006;281:30455-62 pubmed
    ..Together, our data suggest that alphaM1 is divided into two distinct regions. ..
  71. Goulart A, Rexrode K, Cheng S, Rose L, Buring J, Ridker P, et al. Association of genetic variants with the metabolic syndrome in 20,806 white women: The Women's Health Genome Study. Am Heart J. 2009;158:257-262.e1 pubmed publisher
    ..28, 95% CI 0.99-1.65), PAI1 rs1799768 (OR 1.07, 95% CI 1.01-1.14), SCNN1A rs5742912 (OR 1.22, 95% CI 1.01-1.47), and IL1A rs1800587 (OR 1.07, 95% CI 1.01-1...
  72. Ruffieux Daidié D, Staub O. Intracellular ubiquitylation of the epithelial Na+ channel controls extracellular proteolytic channel activation via conformational change. J Biol Chem. 2011;286:2416-24 pubmed publisher
    ..These results present a new paradigm in which an intracellular, post-translational modification (e.g. ubiquitylation) of a transmembrane protein can affect its extracellular conformation. ..
  73. Salker M, Hosseinzadeh Z, Alowayed N, Zeng N, Umbach A, Webster Z, et al. LEFTYA Activates the Epithelial Na+ Channel (ENaC) in Endometrial Cells via Serum and Glucocorticoid Inducible Kinase SGK1. Cell Physiol Biochem. 2016;39:1295-306 pubmed publisher
    ..LEFTYA regulates the expression and activity of ENaC in endometrial epithelial cells via SGK1. Aberrant regulation of SGK1 and ENaC by LEFTYA could contribute to the pathogenesis of unexplained infertility. ..
  74. Ruffieux Daidié D, Poirot O, Boulkroun S, Verrey F, Kellenberger S, Staub O. Deubiquitylation regulates activation and proteolytic cleavage of ENaC. J Am Soc Nephrol. 2008;19:2170-80 pubmed publisher
    ..In summary, these data suggest that Usp2-45 deubiquitylation of ENaC enhances the proteolytic activation of both alphaENaC and gammaENaC, possibly by inducing a conformational change and by interfering with endocytosis, respectively. ..
  75. Perrier R, Boscardin E, Malsure S, Sergi C, Maillard M, Loffing J, et al. Severe Salt-Losing Syndrome and Hyperkalemia Induced by Adult Nephron-Specific Knockout of the Epithelial Sodium Channel ?-Subunit. J Am Soc Nephrol. 2016;27:2309-18 pubmed publisher
    ..We generated adult inducible nephron-specific ?ENaC-knockout mice (Scnn1a(Pax8/LC1)) that exhibit hyperkalemia and body weight loss when kept on a regular-salt diet, thus mimicking PHA-1...
  76. McDonald F, Snyder P, McCray P, Welsh M. Cloning, expression, and tissue distribution of a human amiloride-sensitive Na+ channel. Am J Physiol. 1994;266:L728-34 pubmed
    ..Expression of alpha hENaC in Xenopus oocytes produced currents that were amiloride sensitive and Na+ selective, properties consistent with the function of epithelial Na+ channels in native tissues...
  77. Sugiyama T, Kato N, Ishinaga Y, Yamori Y, Yazaki Y. Evaluation of selected polymorphisms of the Mendelian hypertensive disease genes in the Japanese population. Hypertens Res. 2001;24:515-21 pubmed
    ..However, the present study did not definitively resolve this issue and further investigation is certainly warranted. ..
  78. Araki I, Du S, Kamiyama M, Mikami Y, Matsushita K, Komuro M, et al. Overexpression of epithelial sodium channels in epithelium of human urinary bladder with outlet obstruction. Urology. 2004;64:1255-60 pubmed
    ..The ENaC expressed in the bladder epithelium might be implicated in the mechanosensory transduction in the bladder afferent pathways, thereby inducing detrusor instability by outlet obstruction. ..
  79. Zhou R, Patel S, Snyder P. Nedd4-2 catalyzes ubiquitination and degradation of cell surface ENaC. J Biol Chem. 2007;282:20207-12 pubmed
    ..Together, the data suggest a model in which Nedd4-2 binds to and ubiquitinates ENaC at the cell surface, which targets surface ENaC for degradation, and thus, reduces epithelial Na(+) transport. ..
  80. Juang J, Lu T, Lai L, Ho C, Liu Y, Tsai C, et al. Disease-targeted sequencing of ion channel genes identifies de novo mutations in patients with non-familial Brugada syndrome. Sci Rep. 2014;4:6733 pubmed publisher
    ..Five de novo mutations were identified in four genes (SCNN1A, KCNJ16, KCNB2, and KCNT1) in three BrS patients (20%)...
  81. Bhalla V, Oyster N, Fitch A, Wijngaarden M, Neumann D, Schlattner U, et al. AMP-activated kinase inhibits the epithelial Na+ channel through functional regulation of the ubiquitin ligase Nedd4-2. J Biol Chem. 2006;281:26159-69 pubmed
    ..AMPK-dependent ENaC inhibition may limit cellular Na+ loading under conditions of metabolic stress when AMPK becomes activated. ..
  82. Hills C, Bland R, Bennett J, Ronco P, Squires P. High glucose up-regulates ENaC and SGK1 expression in HCD-cells. Cell Physiol Biochem. 2006;18:337-46 pubmed
    ..Together these data offer a potential explanation for glucose-evoked Na+-resorption and a potential contributory role of SGK1 and ENaCs in development of secondary hypertension, commonly linked to diabetic nephropathy. ..
  83. Wiemuth D, Ke Y, Rohlfs M, McDonald F. Epithelial sodium channel (ENaC) is multi-ubiquitinated at the cell surface. Biochem J. 2007;405:147-55 pubmed
  84. Bardou O, Privé A, Migneault F, Roy Camille K, Dagenais A, Berthiaume Y, et al. K+ channels regulate ENaC expression via changes in promoter activity and control fluid clearance in alveolar epithelial cells. Biochim Biophys Acta. 2012;1818:1682-90 pubmed
    ..In summary, our results disclose that K+ channels regulate alpha-ENaC expression by controlling its promoter activity and thus affect the alveolar function of fluid clearance. ..
  85. Li W, Long C, Renjun L, Zhangxue H, Yin H, Wanwei L, et al. Association of SCNN1A Single Nucleotide Polymorphisms with neonatal respiratory distress syndrome. Sci Rep. 2015;5:17317 pubmed publisher
    ..The SCNN1A gene, which encodes the α-ENaC, might predispose infants to RDS...
  86. Buck T, Jordahl A, Yates M, Preston G, Cook E, Kleyman T, et al. Interactions between intersubunit transmembrane domains regulate the chaperone-dependent degradation of an oligomeric membrane protein. Biochem J. 2017;474:357-376 pubmed publisher
    ..These data indicate that the Lhs1 chaperone selectively recognizes an immature form of ?ENaC, one which has failed to correctly assemble with the other channel subunits via its transmembrane domain. ..
  87. Xu H, Ferro T, Chu S. Cigarette smoke condensate inhibits ENaC alpha-subunit expression in lung epithelial cells. Eur Respir J. 2007;30:633-42 pubmed
  88. Zhang Z, Chou C, Wang J, Liang Y, Ma H. Anionic phospholipids differentially regulate the epithelial sodium channel (ENaC) by interacting with alpha, beta, and gamma ENaC subunits. Pflugers Arch. 2010;459:377-87 pubmed publisher
    ..Further, the data from cell-attached patch-clamp and confocal microscopy experiments indicate that PA, a product of phospholipase D, may provide one of the pathways for inhibition of ENaC by endothelin receptors. ..
  89. Oberfeld B, Ruffieux Daidié D, Vitagliano J, Pos K, Verrey F, Staub O. Ubiquitin-specific protease 2-45 (Usp2-45) binds to epithelial Na+ channel (ENaC)-ubiquitylating enzyme Nedd4-2. Am J Physiol Renal Physiol. 2011;301:F189-96 pubmed publisher
    ..Taken together, the data support the conclusion that Usp2-45 action on ENaC is promoted by various interactions, including through binding to Nedd4-2 that is suggested to position Usp2-45 favorably for ENaC deubiquitylation. ..
  90. Jeggle P, Callies C, Tarjus A, Fassot C, Fels J, Oberleithner H, et al. Epithelial sodium channel stiffens the vascular endothelium in vitro and in Liddle mice. Hypertension. 2013;61:1053-9 pubmed publisher
    ..We conclude that ENaC in the vascular endothelium determines cellular mechanics and hence might participate in the control of vascular function. ..
  91. Ramos M, Trujillano D, Olivar R, Sotillo F, Ossowski S, Manzanares J, et al. Extensive sequence analysis of CFTR, SCNN1A, SCNN1B, SCNN1G and SERPINA1 suggests an oligogenic basis for cystic fibrosis-like phenotypes. Clin Genet. 2014;86:91-5 pubmed publisher
    ..We have performed the extensive molecular analysis of four candidate genes (SCNN1A, SCNN1B, SCNN1G and SERPINA1) in a cohort of 10 uncharacterized patients with CF and CF-like disease...
  92. Jeggle P, Smith E, Stewart A, Haerteis S, Korbmacher C, Edwardson J. Atomic force microscopy imaging reveals the formation of ASIC/ENaC cross-clade ion channels. Biochem Biophys Res Commun. 2015;464:38-44 pubmed publisher
    ..AFM imaging revealed proteins that were decorated by both an antibody and a Fab fragment with an angle of ∼120° between them, indicating the formation of ASIC1a/ENaC heterotrimers. ..