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Epithelial sodium channel

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https://www.readbyqxmd.com/read/27903760/interactions-between-intersubunit-transmembrane-domains-regulate-the-chaperone-dependent-degradation-of-an-oligomeric-membrane-protein
#1
Teresa M Buck, Alexa S Jordahl, Megan E Yates, Mike Preston, Emily Cook, Thomas R Kleyman, Jeffrey L Brodsky
The Epithelial Sodium Channel (ENaC) in kidney regulates blood pressure through control of sodium and volume homeostasis, and in lung ENaC regulates the volume of airway and alveolar fluids.  ENaC is a heterotrimer of homologous α-, β-, and γ-subunits, and assembles in the Endoplasmic Reticulum (ER) before it traffics and functions at the plasma membrane. Improperly folded or orphaned ENaC subunits are subject to ER quality control and targeted for ER associated degradation (ERAD). We previously established that a conserved, ER lumenal, molecular chaperone, Lhs1/GRP170, selects αENaC, but not β- or γENaC, for degradation when the ENaC subunits were individually expressed...
November 30, 2016: Biochemical Journal
https://www.readbyqxmd.com/read/27900368/whole-exome-sequencing-reveals-an-inherited-r566x-mutation-of-the-epithelial-sodium-channel-%C3%AE-subunit-in-a-case-of-early-onset-phenotype-of-liddle-syndrome
#2
Linda M Polfus, Eric Boerwinkle, Richard A Gibbs, Ginger Metcalf, Donna Muzny, Narayanan Veeraraghavan, Megan Grove, Sanjay Shete, Stephanie Wallace, Dianna Milewicz, Neil Hanchard, James R Lupski, Syed Shahrukh Hashmi, Monesha Gupta-Malhotra
To comprehensively evaluate a European-American child with severe hypertension, whole-exome sequencing (WES) was performed on the child and parents, which identified causal variation of the proband's early-onset disease. The proband's hypertension was resistant to treatment, requiring a multiple drug regimen including amiloride, spironolactone, and hydrochlorothiazide. We suspected a monogenic form of hypertension because of the persistent hypokalemia with low plasma levels of renin and aldosterone. To address this, we focused on rare functional variants and indels, and performed gene-based tests incorporating linkage scores and allele frequency and filtered on deleterious functional mutations...
November 2016: Cold Spring Harbor Molecular Case Studies
https://www.readbyqxmd.com/read/27896928/liddle-syndrome-clinical-and-genetic-profiles
#3
Yunying Cui, Anli Tong, Jun Jiang, Fen Wang, Chunyan Li
Liddle syndrome is a rare autosomal dominant monogenic form of hypertension. The authors analyzed clinical and genetic features of 12 cases of Liddle syndrome, the largest sample size ever reported. Clinical data were studied retrospectively. The exon 13 of the β and γ subunits of the epithelial sodium channel were amplified and sequenced in the peripheral blood leukocytes of the patients. The onset age of the 12 patients was 15.5±3.3 years. Their blood pressures were poorly controlled, and serum potassium levels in most patients were <3...
November 29, 2016: Journal of Clinical Hypertension
https://www.readbyqxmd.com/read/27895120/ankyrin-g-expression-regulates-apical-delivery-of-the-epithelial-sodium-channel-enac
#4
Christine A Klemens, Robert S Edinger, Lindsay Kightlinger, Xiaoning Liu, Michael B Butterworth
The epithelial sodium channel (ENaC) is the limiting entry point for Na(+) reabsorption in the distal kidney nephron and is regulated by numerous hormones, including the mineralocorticoid hormone aldosterone. Previously we identified ankyrin G (AnkG), a cytoskeletal protein involved in vesicular transport, as a novel aldosterone-induced protein that can alter Na(+) transport in mouse cortical collecting duct (mCCD) cells. However, the mechanisms underlying AnkG's regulation of Na(+) transport were unknown. Here we report that AnkG expression directly regulates Na(+) transport by altering ENaC activity in the apical membrane...
November 28, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27835672/the-expression-of-water-and-ion-channels-in-diffuse-alveolar-damage-is-not-dependent-on-dad-etiology
#5
Ruy Camargo Pires-Neto, Fabiola Del Carlo Bernardi, Priscila Alves de Araujo, Thais Mauad, Marisa Dolhnikoff
INTRODUCTION: Aquaporins and ion channels are membrane proteins that facilitate the rapid movement of water and solutes across biological membranes. Experimental and in vitro studies reported that the function of these channels and pulmonary edema resolution are impaired in acute lung injury (ALI). Although current evidence indicates that alveolar fluid clearance is impaired in patients with ALI/diffuse alveolar damage (DAD), few human studies have addressed the alterations in pulmonary channels in this clinical condition...
2016: PloS One
https://www.readbyqxmd.com/read/27830759/marked-increases-in-mucociliary-clearance-produced-by-synergistic-secretory-agonists-or-inhibition-of-the-epithelial-sodium-channel
#6
Nam Soo Joo, Jin Hyeok Jeong, Hyung-Ju Cho, Jeffrey J Wine
Mucociliary clearance (MCC) is a critical host innate defense mechanism in airways, and it is impaired in cystic fibrosis (CF) and other obstructive lung diseases. Epithelial fluid secretion and absorption modify MCC velocity (MCCV). We tested the hypotheses that inhibiting fluid absorption accelerates MCCV, whereas inhibiting fluid secretion decelerates it. In airways, ENaC is mainly responsible for fluid absorption, while anion channels, including CFTR and Ca(2+)-activated chloride channels mediate anion/fluid secretion...
November 10, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27815150/solnatide-demonstrates-profound-therapeutic-activity-in-a-rat-model-of-pulmonary-edema-induced-by-acute-hypobaric-hypoxia-and-exercise
#7
Qiquan Zhou, Dong Wang, Yunsheng Liu, Xiaohong Yang, Rudolf Lucas, Bernhard Fischer
BACKGROUND: The synthetic peptide solnatide is a novel pharmacological agent that reduces extravascular lung water, blunts reactive oxygen species production and improves lung function due to its ability to directly activate the epithelial sodium channel ENaC. We aimed to investigate the effect of solnatide in pulmonary edema induced by acute hypobaric hypoxia and exercise in rats, which is considered a model for high altitude pulmonary edema. METHODS: Sprague-Dawley rats were assigned to low altitude control and eight treatment groups...
November 1, 2016: Chest
https://www.readbyqxmd.com/read/27814935/diuretic-resistance
#8
Ewout J Hoorn, David H Ellison
Diuretic resistance is defined as a failure to achieve the therapeutically desired reduction in edema despite a full dose of diuretic. The causes of diuretic resistance include poor adherence to drug therapy or dietary sodium restriction, pharmacokinetic issues, and compensatory increases in sodium reabsorption in nephron sites that are not blocked by the diuretic. To illustrate the pathophysiology and management of diuretic resistance, we describe a patient with nephrotic syndrome. This patient presented with generalized pitting edema and weight gain despite the use of oral loop diuretics...
November 1, 2016: American Journal of Kidney Diseases: the Official Journal of the National Kidney Foundation
https://www.readbyqxmd.com/read/27804084/ion-transport-its-regulation-in-the-endolymphatic-sac-suggestions-for-clinical-aspects-of-meniere-s-disease
#9
REVIEW
Nozomu Mori, Takenori Miyashita, Ryuhei Inamoto, Ai Matsubara, Terushige Mori, Kosuke Akiyama, Hiroshi Hoshikawa
Ion transport and its regulation in the endolymphatic sac (ES) are reviewed on the basis of recent lines of evidence. The morphological and physiological findings demonstrate that epithelial cells in the intermediate portion of the ES are more functional in ion transport than those in the other portions. Several ion channels, ion transporters, ion exchangers, and so on have been reported to be present in epithelial cells of ES intermediate portion. An imaging study has shown that mitochondria-rich cells in the ES intermediate portion have a higher activity of Na(+), K(+)-ATPase and a higher Na(+) permeability than other type of cells, implying that molecules related to Na(+) transport, such as epithelial sodium channel (ENaC), Na(+)-K(+)-2Cl(-) cotransporter 2 (NKCC2) and thiazide-sensitive Na(+)-Cl(-) cotransporter (NCC), may be present in mitochondria-rich cells...
November 1, 2016: European Archives of Oto-rhino-laryngology
https://www.readbyqxmd.com/read/27802315/exosomal-gapdh-from-proximal-tubule-cells-regulate-enac-activity
#10
Kishore Kumar Jella, Ling Yu, Qiang Yue, Daniel Friedman, Billie J Duke, Abdel A Alli
Exosomes are nanometer-scale, cell-derived vesicles that contain various molecules including nucleic acids, proteins, and lipids. These vesicles can release their cargo into adjacent or distant cells and mediate intercellular communication and cellular function. Here we examined the regulation of epithelial sodium channels in mpkCCD cells and distal tubule Xenopus 2F3 cells by exosomes isolated from proximal tubule LLC-PK1 cells. Cultured mpkCCD cells were stained with CTX coupled to a green fluorophore in order to label the cell membranes and freshly isolated exosomes from LLC-PK1 cells were labeled with the red lipophilic dye PKH26 in order to visualize uptake of exosomes into the cells...
2016: PloS One
https://www.readbyqxmd.com/read/27789743/channel-transporter-complexes-an-emerging-theme-in-cell-signaling
#11
Geoffrey W Abbott
In a recent edition of Biochemical Journal, Mistry and colleagues described the discovery of a novel protein complex, formed from the epithelial sodium channel (ENaC) and the sodium chloride cotransporter (NCC) [Biochem. J. (2016) Hoover, S.R]. The importance of these two proteins in the regulation of salt balance and blood pressure has long been known, as has their overlapping expression in the distal convoluted tubule of the kidney. The new study by Mistry et al. now demonstrates their physical interaction in the kidney and when heterologously co-expressed...
November 1, 2016: Biochemical Journal
https://www.readbyqxmd.com/read/27788793/tissue-expression-of-aquaporin-2-is-correlated-to-urine-output-and-allograft-function-in-sensitized-kidney-transplant-patients
#12
K Klein, S Rübenacker, S M Schaefer, L P Kihm, V Schwenger, S Macher-Goeppinger, P Schemmer, C Süsald, M Zeier, C Morath, L E Becker
BACKGROUND: Salt and water disturbances often occur during acute kidney allograft dysfunction that contribute to graft failure, but this condition has been poorly investigated in the alloreactivity setting. We evaluated the tissue expression of aquaporins (AQP1 and AQP2) and the epithelial sodium channel (ENAC) in kidney biopsy specimens from sensitized kidney transplant recipients. METHODS: Eighty-six biopsy specimens from 33 sensitized patients were divided into 3 groups according to clinical context: time-zero (n = 9), protocol (n = 9), and indication (n = 68)...
October 2016: Transplantation Proceedings
https://www.readbyqxmd.com/read/27780255/an-optimised-human-cell-culture-model-for-alveolar-epithelial-transport
#13
Hui Ren, Nigel P Birch, Vinod Suresh
Robust and reproducible in vitro models are required for investigating the pathways involved in fluid homeostasis in the human alveolar epithelium. We performed functional and phenotypic characterisation of ion transport in the human pulmonary epithelial cell lines NCI-H441 and A549 to determine their similarity to primary human alveolar type II cells. NCI-H441 cells exhibited high expression of junctional proteins ZO-1, and E-cadherin, seal-forming claudin-3, -4, -5 and Na+-K+-ATPase while A549 cells exhibited high expression of pore-forming claudin-2...
2016: PloS One
https://www.readbyqxmd.com/read/27777930/characterization-of-aqps-in-mouse-rat-and-human-colon-and-their-selective-regulation-by-bile-acids
#14
Jonathan Yde, Stephen Keely, Qi Wu, Johan F Borg, Natalia Lajczak, Aoife O'Dwyer, Peter Dalsgaard, Robert A Fenton, Hanne B Moeller
In normal individuals, the epithelium of the colon absorbs 1.5-2 l of water a day to generate dehydrated feces. However, in the condition of bile acid malabsorption (BAM), an excess of bile acids in the colon results in diarrhea. Several studies have attempted to address the mechanisms contributing to BAM induced by various bile acids. However, none have addressed a potential dysregulation of aquaporin (AQP) water channels, which are responsible for the majority of transcellular water transport in epithelial cells, as a contributing factor to the onset of diarrhea and the pathogenesis of BAM...
2016: Frontiers in Nutrition
https://www.readbyqxmd.com/read/27762337/formaldehyde-impairs-transepithelial-sodium-transport
#15
Yong Cui, Huiming Li, Sihui Wu, Runzhen Zhao, Deyi Du, Yan Ding, Hongguang Nie, Hong-Long Ji
Unsaturated oxidative formaldehyde is a noxious aldehyde in cigarette smoke that causes edematous acute lung injury. However, the mechanistic effects of formaldehyde on lung fluid transport are still poorly understood. We examined how formaldehyde regulates human epithelial sodium channels (ENaC) in H441 and expressed in Xenopus oocytes and exposed mice in vivo. Our results showed that formaldehyde reduced mouse transalveolar fluid clearance in vivo. Formaldehyde caused a dose-dependent inhibition of amiloride-sensitive short-circuit Na(+) currents in H441 monolayers and of αβγ-ENaC channel activity in oocytes...
October 20, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27755216/altered-prostasin-cap1-prss8-expression-favors-inflammation-and-tissue-remodeling-in-dss-induced-colitis
#16
Anna Keppner, Sumedha Malsure, Antoine Nobile, Muriel Auberson, Olivier Bonny, Edith Hummler
BACKGROUND: Inflammatory bowel diseases (IBD) including ulcerative colitis and Crohn's disease are diseases with impaired epithelial barrier function. We aimed to investigate whether mutated prostasin and thus, reduced colonic epithelial sodium channel activity predisposes to develop an experimentally dextran sodium sulfate (DSS)-induced colitis. METHODS: Wildtype, heterozygous (fr/+), and homozygous (fr/fr) prostasin-mutant rats were treated 7 days with DSS followed by 7 days of recovery and analyzed with respect to histology, clinicopathological parameters, inflammatory marker mRNA transcript expression, and sodium transporter protein expression...
October 12, 2016: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/27754097/os-21-02-connecting-tubule-glomerular-feedback-ctgf-in-renal-hemodynamics-and-blood-pressure-regulation-after-unilateral-nephrectomy-unx
#17
Cesar Romero, Sumit Monu, Glauber Cabral, Robert Knight, Oscar Carretero
OBJECTIVE: Renal hemodynamics is critical for regulation of glomerular filtration (GFR), sodium excretion and blood pressure (BP), and it depends on myogenic response, tubuloglomerular feedback (TGF) and connecting tubule-glomerular feedback (CTGF). CTGF dilates afferent arteriole in response to high sodium in connecting tubule (CNT), counteracting and resetting TGF; and increasing the plasma flow and glomerular pressure favoring sodium excretion. CTGF is initiated by epithelial sodium channel (ENaC) activation in CNT and inhibited by ENaC blocker Benzamil...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27717709/cns-sites-activated-by-renal-pelvic-epithelial-sodium-channels-enacs-in-response-to-hypertonic-saline-in-awake-rats
#18
Vanessa S Goodwill, Christopher Terrill, Ian Hopewood, Arthur D Loewy, Mark M Knuepfer
In some patients, renal nerve denervation has been reported to be an effective treatment for essential hypertension. Considerable evidence suggests that afferent renal nerves (ARN) and sodium balance play important roles in the development and maintenance of high blood pressure. ARN are sensitive to sodium concentrations in the renal pelvis. To better understand the role of ARN, we infused isotonic or hypertonic NaCl (308 or 500mOsm) into the left renal pelvis of conscious rats for two 2hours while recording arterial pressure and heart rate...
September 22, 2016: Autonomic Neuroscience: Basic & Clinical
https://www.readbyqxmd.com/read/27682266/amiloride-modifies-the-progression-of-lithium-induced-renal-interstitial-fibrosis
#19
Priyakshi Kalita-DE Croft, Jennifer J Bedford, John P Leader, Robert J Walker
AIM: Long-term administration of lithium has been associated with the development of a chronic interstitial fibrosis in addition to nephrogenic diabetes insipidus (NDI). Earlier studies have demonstrated that amiloride, by blocking the epithelial sodium channel ENaC and thus preventing lithium uptake into the principal cells of the collecting ducts, can partially reverse lithium-induced NDI. However, there are no long-term studies examining whether or not amiloride also modifies the progressive chronic interstitial fibrosis and tubular atrophy often evident with long term lithium exposure...
September 28, 2016: Nephrology
https://www.readbyqxmd.com/read/27664711/mineralocorticoid-receptor-antagonists-a-new-sprinkle-of-salt-and-youth
#20
Olivera Stojadinovic, Linsey E Lindley, Ivan Jozic, Marjana Tomic-Canic
Skin atrophy and impaired cutaneous wound healing are the recognized side effects of topical glucocorticoid (GC) therapy. Although GCs have high affinity for the glucocorticoid receptor, they also bind and activate the mineralocorticoid receptor. In light of this, one can speculate that some of the GC-mediated side effects can be remedied by blocking activation of the mineralocorticoid receptor. Indeed, according to Nguyen et al., local inhibition of the mineralocorticoid receptor via antagonists (spironolactone, canrenoate, and eplerenone) rescues GC-induced delayed epithelialization and accelerates wound closure in diabetic animals by targeting epithelial sodium channels and stimulating keratinocyte proliferation...
October 2016: Journal of Investigative Dermatology
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