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Epithelial sodium channel

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https://www.readbyqxmd.com/read/29767556/hydronephrosis-is-associated-with-elevated-plasmin-in-urine-in-pediatric-patients-and-rats-and-changes-in-ncc-and-%C3%AE-enac-abundance-in-rat-kidney
#1
Rikke Zachar, Ammar Al-Mashhadi, Henrik Dimke, Per Svenningsen, Boye L Jensen, Mattias Carlström
Obstruction of urine flow at the level of the pelvo-ureteric junction (UPJO) and subsequent development of hydronephrosis is one of the most common congenital renal malformations. UPJO is associated with development of salt-sensitive hypertension, which is set by the obstructed kidney, and with a stimulated renin-angiotensin-aldosterone system (RAAS) in rodent models. This study aimed at investigating the hypothesis that i) in pediatric patients with UPJO the RAAS is activated prior to surgical relief of the obstruction; ii) in rats with UPJO the RAAS activation is reflected by increased abundance of renal aldosterone-stimulated Na+ transporters; and iii) the injured UPJO kidney allows aberrant filtration of plasminogen leading to proteolytic activation of the epithelial sodium channel gamma subunit (γ-ENaC)...
May 16, 2018: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29757959/association-of-genetic-variation-in-the-epithelial-sodium-channel-gene-with-urinary-sodium-excretion-and-blood-pressure
#2
Yoon Jung Yang, Jihye Kim, Chang Keun Kwock
This study was performed to investigate whether genetic variation in the epithelial sodium channel (ENaC) is associated with 24-h urinary sodium excretion and blood pressure. A total of 3345 participants of the KoGES_Ansan and Ansung study were eligible for this study. Genomic DNA samples were isolated from peripheral blood and genotyped on the Affymetrix Genome-Wide Human SNP Array 5.0. Thirty-four single nucleotide polymorphisms (SNPs) were extracted for gene regions ( SCNN1A , SCNN1B , and SCNN1G ) as additive components by using Plink...
May 14, 2018: Nutrients
https://www.readbyqxmd.com/read/29750923/ion-channel-modulators-in-cystic-fibrosis
#3
REVIEW
Martina Gentzsch, Marcus A Mall
Cystic fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene and remains one of the most common life-shortening genetic diseases affecting the lung and other organs. CFTR functions as a cAMP-dependent anion channel that transports chloride and bicarbonate across epithelial surfaces and disruption of these ion transport processes plays a central role in the pathogenesis of CF. These findings provided the rationale for pharmacological modulation of ion transport, either by targeting mutant CFTR or alternative ion channels that can compensate for CFTR dysfunction, as a promising therapeutic approach...
May 8, 2018: Chest
https://www.readbyqxmd.com/read/29748250/effective-silencing-of-enac-by-sirna-delivered-with-epithelial-targeted-nanocomplexes-in-human-cystic-fibrosis-cells-and-in-mouse-lung
#4
Aristides D Tagalakis, Mustafa M Munye, Rositsa Ivanova, Hanpeng Chen, Claire M Smith, Ahmad M Aldossary, Luca Z Rosa, Dale Moulding, Josephine L Barnes, Konstantinos N Kafetzis, Stuart A Jones, Deborah L Baines, Guy W J Moss, Christopher O'Callaghan, Robin J McAnulty, Stephen L Hart
INTRODUCTION: Loss of the cystic fibrosis transmembrane conductance regulator in cystic fibrosis (CF) leads to hyperabsorption of sodium and fluid from the airway due to upregulation of the epithelial sodium channel (ENaC). Thickened mucus and depleted airway surface liquid (ASL) then lead to impaired mucociliary clearance. ENaC regulation is thus a promising target for CF therapy. Our aim was to develop siRNA nanocomplexes that mediate effective silencing of airway epithelial ENaC in vitro and in vivo with functional correction of epithelial ion and fluid transport...
May 10, 2018: Thorax
https://www.readbyqxmd.com/read/29700291/protectin-dx-increases-alveolar-fluid-clearance-in-rats-with-lipopolysaccharide-induced-acute-lung-injury
#5
Xiao-Jun Zhuo, Yu Hao, Fei Cao, Song-Fan Yan, Hui Li, Qian Wang, Bi-Huan Cheng, Bin-Yu Ying, Fang Gao Smith, Sheng-Wei Jin
Acute respiratory distress syndrome is a life-threatening critical syndrome resulting largely from the accumulation of and the inability to clear pulmonary edema. Protectin DX, an endogenously produced lipid mediator, is believed to exert anti-inflammatory and pro-resolution effects. Protectin DX (5 µg/kg) was injected i.v. 8 h after LPS (14 mg/kg) administration, and alveolar fluid clearance was measured in live rats (n = 8). In primary rat ATII epithelial cells, protectin DX (3.605 × 10-3  mg/l) was added to the culture medium with LPS for 6 h...
April 27, 2018: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29692722/the-deletion-of-endothelial-sodium-channel-%C3%AE-%C3%AE-enac-impairs-endothelium-dependent-vasodilation-and-endothelial-barrier-integrity-in-endotoxemia-in-vivo
#6
Magdalena Sternak, Anna Bar, Mateusz G Adamski, Tasnim Mohaissen, Brygida Marczyk, Anna Kieronska, Marta Stojak, Kamil Kus, Antoine Tarjus, Frederic Jaisser, Stefan Chlopicki
The role of epithelial sodium channel (ENaC) activity in the regulation of endothelial function is not clear. Here, we analyze the role of ENaC in the regulation of endothelium-dependent vasodilation and endothelial permeability in vivo in mice with conditional αENaC subunit gene inactivation in the endothelium (endo-αENaCKO mice) using unique MRI-based analysis of acetylcholine-, flow-mediated dilation and vascular permeability. Mice were challenged or not with lipopolysaccharide (LPS, from Salmonella typhosa , 10 mg/kg, i...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29664060/specialized-pro-resolving-mediators-regulate-alveolar-fluid-clearance-during-acute-respiratory-distress-syndrome
#7
REVIEW
Qian Wang, Song-Fan Yan, Yu Hao, Sheng-Wei Jin
Objective: Acute respiratory distress syndrome (ARDS) is an acute and lethal clinical syndrome that is characterized by the injury of alveolar epithelium, which impairs active fluid transport in the lung, and impedes the reabsorption of edema fluid from the alveolar space. This review aimed to discuss the role of pro-resolving mediators on the regulation of alveolar fluid clearance (AFC) in ARDS. Data Sources: Articles published up to September 2017 were selected from the PubMed, with the keywords of "alveolar fluid clearance" or "lung edema" or "acute lung injury" or "acute respiratory distress syndrome", and "specialized pro-resolving mediators" or "lipoxin" or "resolvin" or "protectin" or "maresin" or "alveolar epithelial cells" or "aspirin-triggered lipid mediators" or "carbon monoxide and heme oxygenase" or "annexin A1"...
April 20, 2018: Chinese Medical Journal
https://www.readbyqxmd.com/read/29605410/environmentally-relevant-levels-of-bisphenol-a-affect-uterine-decidualization-and-embryo-implantation-through-the-estrogen-receptor-serum-and-glucocorticoid-regulated-kinase-1-epithelial-sodium-ion-channel-%C3%AE-subunit-pathway-in-a-mouse-model
#8
Mu Yuan, Minhao Hu, Yiyun Lou, Qijing Wang, Luna Mao, Qitao Zhan, Fan Jin
OBJECTIVE: To investigate whether bisphenol A (BPA) exposure is associated with uterine decidualization and embryo implantation failure in mice. DESIGN: Experimental animal study and in vitro study. SETTING: University-based infertility center. ANIMAL(S): ICR mice. INTERVENTION(S): Mice treated with different doses of BPA; Ishikawa cells cultured in medium of different concentrations of BPA. MAIN OUTCOME MEASURE(S): Embryo implantation sites, uterine weight, quantitative real-time reverse transcriptase-polymerase chain reaction, Western blot analysis, hematoxylin and eosin staining, and immunohistochemical, cell proliferation, and statistical analyses...
April 2018: Fertility and Sterility
https://www.readbyqxmd.com/read/29580127/epithelial-sodium-channel-blockade-and-new-%C3%AE-enac-polymorphisms-among-normotensive-and-hypertensive-adult-nigerians
#9
Simiat O Elias, Olusoga A Sofola, Smith I Jaja
We sought to determine the effect of amiloride on blood pressure (BP) and the presence of polymorphisms of the β-subunit of the epithelial sodium channel (ENaC) among normotensive (NT) and hypertensive (HT) Nigerians. Healthy volunteers-47 NT and 53 age-matched HT were recruited after giving informed consent. Subjects were salt-loaded with 200 mmol of NaCl daily for 5 days. Following a week washout period, salt-loading was repeated in addition to the administration of 5 mg amiloride daily for five days. Blood pressure, plasma and urine electrolytes were measured at baseline, after salt-loading and after salt-loading plus amiloride...
March 26, 2018: Clinical and Experimental Hypertension: CHE
https://www.readbyqxmd.com/read/29576549/incorporation-of-the-delta-subunit-into-the-epithelial-sodium-channel-enac-generates-protease-resistant-enacs-in-xenopus-laevis
#10
Lukas Wichmann, Kirsty Sophia Vowinkel, Alexander Perniss, Ivan Manzini, Mike Althaus
The epithelial sodium channel (ENaC) is a critical regulator of vertebrate electrolyte homeostasis. ENaC is the only constitutively open ion channel in the degenerin/ENaC protein family, and its expression, membrane abundance, and open probability therefore are tightly controlled. The canonical ENaC is composed of three subunits (α, β and γ), but a fourth δ-subunit may replace α and form atypical δβγ-ENaCs. Using Xenopus laevis as a model, here we found that mRNAs of the α- and δ-subunits are differentially expressed in different tissues and that δ-ENaC predominantly is present in the urogenital tract...
March 25, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29547542/transepithelial-fluid-and-salt-re-absorption-regulated-by-cgk2-signals
#11
REVIEW
Jianjun Chang, Yan Ding, Zhiyu Zhou, Hong-Guang Nie, Hong-Long Ji
Transepithelial fluid and salt re-absorption in epithelial tissues play an important role in fluid and salt homeostasis. In absorptive epithelium, fluid and salt flux is controlled by machinery mainly composed of epithelial sodium channels (ENaC), cystic fibrosis transmembrane conductance regulator (CFTR), Na⁺/H⁺ exchanger (NHE), aquaporin, and sodium potassium adenosine triphosphatase (Na⁺/K⁺-ATPase). Dysregulation of fluid and salt transport across epithelium contributes to the pathogenesis of many diseases, such as pulmonary edema and cystic fibrosis...
March 16, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29534496/liddle-syndrome-review-of-the-literature-and-description-of-a-new-case
#12
REVIEW
Martina Tetti, Silvia Monticone, Jacopo Burrello, Patrizia Matarazzo, Franco Veglio, Barbara Pasini, Xavier Jeunemaitre, Paolo Mulatero
Liddle syndrome is an inherited form of low-renin hypertension, transmitted with an autosomal dominant pattern. The molecular basis of Liddle syndrome resides in germline mutations of the SCNN1A , SCNN1B and SCNN1G genes, encoding the α, β, and γ-subunits of the epithelial Na⁺ channel (ENaC), respectively. To date, 31 different causative mutations have been reported in 72 families from four continents. The majority of the substitutions cause an increased expression of the channel at the distal nephron apical membrane, with subsequent enhanced renal sodium reabsorption...
March 11, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29526865/oxymatrine-attenuates-lipopolysaccharide-induced-acute-lung-injury-by-activating-the-epithelial-sodium-channel-and-suppressing-the-jnk-signaling-pathway
#13
Bingji Jin, Hong Jin
The epithelial sodium channel (ENaC) and mitogen-activated protein kinase (MAPK) pathway have been reported to be associated with the progression of acute lung injury (ALI). Oxymatrine (OMT) alone or combined with other drugs can ameliorate paraquat- or oleic acid-induced lung injury. However, the effect of OMT on lipopolysaccharide (LPS)-induced ALI remains unknown. The aim of the present study was to evaluate whether OMT can attenuate LPS-induced ALI through regulation of the ENaC and MAPK pathway using an ALI mouse model...
March 9, 2018: Experimental Animals
https://www.readbyqxmd.com/read/29513651/gating-mechanisms-of-acid-sensing-ion-channels
#14
Nate Yoder, Craig Yoshioka, Eric Gouaux
Acid-sensing ion channels (ASICs) are trimeric, proton-gated and sodium-selective members of the epithelial sodium channel/degenerin (ENaC/DEG) superfamily of ion channels and are expressed throughout vertebrate central and peripheral nervous systems. Gating of ASICs occurs on a millisecond time scale and the mechanism involves three conformational states: high pH resting, low pH open and low pH desensitized. Existing X-ray structures of ASIC1a describe the conformations of the open and desensitized states, but the structure of the high pH resting state and detailed mechanisms of the activation and desensitization of the channel have remained elusive...
March 15, 2018: Nature
https://www.readbyqxmd.com/read/29489063/plasma-kallikrein-activates-the-epithelial-sodium-channel-in-vitro-but-is-not-essential-for-volume-retention-in-nephrotic-mice
#15
S Haerteis, A Schork, T Dörffel, B N Bohnert, R Nacken, M Wörn, M Xiao, D Essigke, A Janessa, A H Schmaier, E P Feener, H-U Häring, M Bertog, C Korbmacher, F Artunc
AIM: Recent work has demonstrated that activation of the epithelial sodium channel (ENaC) by aberrantly filtered serine proteases causes sodium retention in nephrotic syndrome. The aim of this study was to elucidate a potential role of plasma kallikrein (PKLK) as a candidate serine protease in this context. METHODS: We analysed PKLK in the urine of patients with chronic kidney disease (CKD, n = 171) and investigated its ability to activate human ENaC expressed in Xenopus laevis oocytes...
February 28, 2018: Acta Physiologica
https://www.readbyqxmd.com/read/29483157/mechanism-of-hyperkalemia-induced-metabolic-acidosis
#16
Autumn N Harris, P Richard Grimm, Hyun-Wook Lee, Eric Delpire, Lijuan Fang, Jill W Verlander, Paul A Welling, I David Weiner
Background Hyperkalemia in association with metabolic acidosis that are out of proportion to changes in glomerular filtration rate defines type 4 renal tubular acidosis (RTA), the most common RTA observed, but the molecular mechanisms underlying the associated metabolic acidosis are incompletely understood. We sought to determine whether hyperkalemia directly causes metabolic acidosis and, if so, the mechanisms through which this occurs. Methods We studied a genetic model of hyperkalemia that results from early distal convoluted tubule (DCT)-specific overexpression of constitutively active Ste20/SPS1-related proline-alanine-rich kinase (DCT-CA-SPAK)...
May 2018: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/29453757/localization-of-epithelial-sodium-channel-enac-and-cftr-in-the-germinal-epithelium-of-the-testis-sertoli-cells-and-spermatozoa
#17
Sachin Sharma, Aaron Hanukoglu, Israel Hanukoglu
Spermatogenesis starts within the seminiferous tubules of the testis by mitotic division of spermatogonia that produces spermatocytes. Meiotic division of these spermatocytes produces haploid spermatids that differentiate into spermatozoa. In this study, we examined the expression of ENaC and CFTR (a Cl- channel) in rat testicular sections using confocal microscopic immunofluorescence. The structural integrity of the seminiferous tubule sections was verified by precise phalloidin staining of the actin fibers located abundantly at both basal and adluminal tight junctions...
April 2018: Journal of Molecular Histology
https://www.readbyqxmd.com/read/29413762/the-epithelial-sodium-channel-%C3%AE-enac-is-a-downstream-therapeutic-target-of-ascl1-in-pulmonary-neuroendocrine-tumors
#18
Min He, Shanshan Liu, Sachith Gallolu Kankanamalage, Mark D Borromeo, Luc Girard, Adi F Gazdar, John D Minna, Jane E Johnson, Melanie H Cobb
Small cell lung cancer (SCLC) is an aggressive neuroendocrine carcinoma, designated as a recalcitrant cancer by the National Cancer Institute, in urgent need of new rational therapeutic targets. Previous studies have determined that the basic helix-loop-helix transcription factor achaete-scute homolog 1 (ASCL1) is essential for the survival and progression of a fraction of pulmonary neuroendocrine cancer cells, which include both SCLC and a subset of non-SCLC. Previously, to understand how ASCL1 initiates tumorigenesis in pulmonary neuroendocrine cancer and identify the transcriptional targets of ASCL1, whole-genome RNA-sequencing analysis combined with chromatin immunoprecipitation-sequencing was performed with a series of lung cancer cell lines...
April 2018: Translational Oncology
https://www.readbyqxmd.com/read/29396543/ouabagenin-is-a-naturally-occurring-lxr-ligand-without-causing-hepatic-steatosis-as-a-side-effect
#19
Satoru Tamura, Maiko Okada, Shigeaki Kato, Yasuharu Shinoda, Norifumi Shioda, Kohji Fukunaga, Kumiko Ui-Tei, Minoru Ueda
Ouabagenin (OBG) is an aglycone of the cardiotonic steroid ouabain and until now was considered a biologically inactive biosynthetic precursor. Herein, we revealed that OBG functions as a novel class of ligand for the liver X receptor (LXR). Luciferase reporter assays and in silico docking studies suggested that OBG has LXR-selective agonistic activity. In addition, OBG repressed the expression of epithelial sodium channel (ENaC), a LXR target gene, without causing hepatic steatosis, a typical side effect of conventional LXR ligands...
February 2, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29373035/epithelial-na-channel-enac-differentially-contributes-to-shear-stress-mediated-vascular-responsiveness-in-carotid-and-mesenteric-arteries-from-mice
#20
Zoe Ashley, Sama Mugloo, Fiona J McDonald, Martin Fronius
A potential "new player" in arteries for mediating shear stress responses is the Epithelial Sodium Channel (ENaC). ENaC's contribution as shear sensor in intact arteries, and particularly different types of arteries (conduit and resistance) is unknown. We investigated the role of ENaC in both conduit (carotid) and resistance (3rd order mesenteric) arteries isolated from C57Bl/6J mice. Vessel characteristics were determined at baseline (60 mmHg, no-flow), in response to increased intraluminal pressure and shear stress using a pressure myograph...
January 26, 2018: American Journal of Physiology. Heart and Circulatory Physiology
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