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Epithelial sodium channel

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https://www.readbyqxmd.com/read/29351436/therapeutic-attenuation-of-the-epithelial-sodium-channel-with-a-splunc1-derived-peptide-in-airway-diseases
#1
James F Collawn, Rafal Bartoszewski, Ahmad Lazrak, Sadis Matalon
The airway surface liquid (ASL) coats the lining of the airways and allows for efficient cilial movement and therefore effective mucociliary transport. Cell surface channels regulate the hydration status of the ASL and the two critical channels in the process are the cystic fibrosis transmembrane conductance regulator (CFTR) and the amiloride-sensitive epithelial sodium channel (ENaC). In cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD) there is loss of CFTR function or compromised CFTR function in chronic bronchitis, respectively...
January 4, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/29305116/urine-albumin-is-a-superior-predictor-of-preeclampsia-compared-to-urine-plasminogen-in-type-i-diabetes-patients
#2
Lise Hald Nielsen, Boye L Jensen, Jens Fuglsang, Lise Lotte Torvin Andersen, Dorte Møller Jensen, Jan Stener Jørgensen, Gitte Kitlen, Per Ovesen
Pregnant women with type I diabetes mellitus (T1DM) are at increased risk of developing preeclampsia (PE). Plasminogen is aberrantly filtrated from plasma into tubular fluid in PE patients and activated to plasmin. Plasmin activates the epithelial sodium channel in the collecting ducts potentially causing impaired sodium excretion, suppression of the renin-angiotensin-aldosterone system, and hypertension in PE. The objective of the study was to test whether urinary total plasmin(ogen)/creatinine ratio and plasma concentration of aldosterone were better predictors of PE in pregnant women with T1DM compared with urine albumin and haemoglobin A1C...
December 13, 2017: Journal of the American Society of Hypertension: JASH
https://www.readbyqxmd.com/read/29295861/splunc1-is-an-allosteric-modulator-of-the-epithelial-sodium-channel
#3
Christine Seulki Kim, Saira Ahmad, Tongde Wu, William G Walton, Matthew R Redinbo, Robert Tarran
Cystic fibrosis (CF) is a common genetic disease with significantly increased mortality. CF airways exhibit ion transport abnormalities, including hyperactivity of the epithelial Na+ channel (ENaC). Short-palate lung and nasal epithelial clone 1 (SPLUNC1) is a multifunctional innate defense protein that is secreted into the airway lumen. We have previously demonstrated that SPLUNC1 binds to and inhibits ENaC to maintain fluid homeostasis in airway epithelia and that this process fails in CF airways. Despite this, how SPLUNC1 actually regulates ENaC is unknown...
January 2, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29289532/zinc-deficiency-via-a-splice-switch-in-zinc-importer-zip2-slc39a2-causes-cystic-fibrosis-associated-muc5ac-hypersecretion-in-airway-epithelial-cells
#4
Shunsuke Kamei, Haruka Fujikawa, Hirofumi Nohara, Keiko Ueno-Shuto, Kasumi Maruta, Ryunosuke Nakashima, Taisei Kawakami, Chizuru Matsumoto, Yuki Sakaguchi, Tomomi Ono, Mary Ann Suico, Richard C Boucher, Dieter C Gruenert, Toru Takeo, Naomi Nakagata, Jian-Dong Li, Hirofumi Kai, Tsuyoshi Shuto
Airway mucus hyperproduction and fluid imbalance are important hallmarks of cystic fibrosis (CF), the most common life-shortening genetic disorder in Caucasians. Dysregulated expression and/or function of airway ion transporters, including cystic fibrosis transmembrane conductance regulator (CFTR) and epithelial sodium channel (ENaC), have been implicated as causes of CF-associated mucus hypersecretory phenotype. However, the contributory roles of other substances and transporters in the regulation of CF airway pathogenesis remain unelucidated...
December 20, 2017: EBioMedicine
https://www.readbyqxmd.com/read/29283974/the-role-of-distal-tubule-and-collecting-duct-sodium-reabsorption-in-sunitinib-induced-hypertension
#5
Jeannine Witte, Josephine Lampe, Anna Koenen, Ines Urbaneck, Antje Steinbach, Rainer Rettig, Olaf Grisk
OBJECTIVE: Antiangiogenic receptor tyrosine kinase inhibitors (RTKI) induce arterial hypertension which may limit their use. Renal fractional sodium excretion (FENa) is reduced in early RTKI-induced hypertension, whereas fractional lithium excretion is unaltered. Therefore, we tested the hypothesis that activated distal tubule and collecting duct sodium reabsorption contributes to RTKI-induced hypertension. METHODS: Amiloride-sensitive and hydrochlorothiazide (HCTZ)-sensitive fractional sodium reabsorption (FRNa) and renal epithelial sodium channel (ENaC) as well as sodium chloride cotransporter (NCC) abundances were determined in sunitinib-treated and control rats...
December 27, 2017: Journal of Hypertension
https://www.readbyqxmd.com/read/29246398/doca-salt-hypertension-alters-period1-and-orexin-related-gene-expression-in-the-medulla-and-hypothalamus-of-male-rats-diurnal-influences
#6
M E Hernandez, J M Watkins, J Vu, L F Hayward
In peripheral tissues, aldosterone alters expression of multiple genes, including the clock gene Period 1 (Per1), 11 beta-hydroxysteroid dehydrogenase-2 (11-HSD2), and α-ENAC, the epithelial sodium channel subunit. We evaluated the impact of chronic aldosterone exposure (DOCA) and salt intake on nocturnal changes in gene expression in the male Sprague Dawley rat brain. Additionally, genes associated with the orexin (ORX) system were also evaluated based on the role of this neuropeptide in arousal, feeding and hypertension and an interconnection with Per1 expression...
December 9, 2017: Autonomic Neuroscience: Basic & Clinical
https://www.readbyqxmd.com/read/29230238/fluid-retention-caused-by-rosiglitazone-is-related-to-increases-in-aqp2-and-%C3%AE-enac-membrane-expression
#7
Jinghua Xu, Mingyue Pan, Xiaoli Wang, Lishi Xu, Lanfang Li, Cheng Xu
Peroxisome proliferator activated receptor-γ (PPARγ) is a ligand-activated transcription factor of the nuclear hormone receptor superfamily. The decreased phosphorylation of PPARγ due to rosiglitazone (ROS) is the main reason for the increased insulin sensitivity caused by this antidiabetic drug. However, there is no clear evidence whether the nuclear translocation of p-PPARγ stimulated by ROS is related to fluid retention. It is also unclear whether the translocation of p-PPARγ is associated with the change of aquaporin-2 (AQP2) and epithelial sodium channel α subunit (αENaC) in membranes, cytoplasm, and nucleus...
2017: PPAR Research
https://www.readbyqxmd.com/read/29229744/three-reportedly-unrelated-families-with-liddle-syndrome-inherited-from-a-common-ancestor
#8
Luca Pagani, Yoan Diekmann, Marco Sazzini, Sara De Fanti, Maurizio Rondinelli, Enrico Farnetti, Bruno Casali, Amelia Caretto, Francesca Novara, Orsetta Zuffardi, Paolo Garagnani, Franco Mantero, Mark G Thomas, Donata Luiselli, Ermanno Rossi
Liddle syndrome is considered a rare Mendelian hypertension. We have previously described 3 reportedly unrelated families, native of an Italian area around the Strait of Messina, carrying the same mutation (βP617L) of the epithelial sodium channel. The aims of our study were (1) to evaluate whether a close genomic relationship exists between the 3 families through the analysis of mitochondrial DNA and Y chromosome; and (2) to quantify the genomic relatedness between the patients with Liddle syndrome belonging to the 3 families and assess the hypothesis of a mutation shared through identity by descent...
December 11, 2017: Hypertension
https://www.readbyqxmd.com/read/29180450/knockout-of-mitochondrial-voltage-dependent-anion-channel-type-3-increases-reactive-oxygen-species-ros-levels-and-alters-renal-sodium-transport
#9
Li Zou, Valerie Linck, Yu-Jia Zhai, Laura Galarza-Paez, Linda Li, Qiang Yue, Otor Al-Khalili, Hui-Fang Bao, He-Ping Ma, Tiffany L Thai, Jundong Jiao, Douglas C Eaton
It has been suggested that voltage-dependent anion channels (VDACs) control the release of superoxide from mitochondria. We have previously shown that reactive oxygen species (ROS) such as superoxide (O2-) and hydrogen peroxide (H2O2) stimulate epithelial sodium channels (ENaCs) in sodium-transporting epithelial tissue including cortical collecting duct (CCD) principal cells. Therefore, we hypothesized that VDACs could regulate ENaC by modulating cytosolic ROS levels. Herein, we find that VDAC3-knockout(KO) mice can maintain normal salt and water balance on low-salt and high-salt diets...
November 27, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29180329/-effects-of-aldosterone-on-osteoblast-proliferation-differentiation-and-osteogenic-gene-expressions-in-vitro
#10
Jun Chen, Fang-Mei Xie, Xin Lin, Si-Hui Lin, Guo-Zhu Yang, Li Lu, Xing-Yan Lu, Qing-Nan Li
OBJECTIVE: To study the effect of aldosterone on cell proliferation, alkaline phosphatase (AKP) activity and osteogenic gene expression in rat osteoblasts and explore the mechanisms. METHODS: Osteoblasts isolated from the skull of neonatal SD rats by enzyme digestion were cultured and treated with different concentrations of aldosterone. The cell proliferation and AKP activity were evaluated using CCK-8 assay kit and AKP assay kit, respectively. The effects of aldosterone on mRNA and protein expressions of the osteogenic genes and epithelial sodium channel (ENaC) gene were investigated using semi-quantitative PCR and Western blotting...
November 20, 2017: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
https://www.readbyqxmd.com/read/29179210/enacs-as-both-effectors-and-regulators-of-mirnas-in-lung-epithelial-development-and-regeneration
#11
Yan Ding, Runzhen Zhao, Xiaoli Zhao, Michael A Matthay, Hong-Guang Nie, Hong-Long Ji
Epithelial sodium channels (ENaC) play an important role in re-absorbing excessive luminal fluid by building up an osmotic Na+ gradient across the tight epithelium in the airway, the lung, the kidney, and the colon. The ENaC is a major pathway for retention of salt in kidney too. MicroRNAs (miRs), a group of non-coding RNAs that regulate gene expression at the post-transcriptional level, have emerged as a novel class of regulators for ENaC. Given the ENaC pathway is crucial for maintaining fluid homeostasis in the lung and the kidney and other cavities, we summarized the cross-talk between ENaC and miRs and recapitulated the underlying regulatory factors, including aldosterone, transforming growth factor-β1, and vascular endothelial growth factor-A in the lung and other epithelial tissues/organs...
November 27, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29154907/an-integrated-mathematical-epithelial-cell-model-for-airway-surface-liquid-regulation-by-mechanical-forces
#12
Dan Wu, Richard C Boucher, Brian Button, Timothy Elston, Ching-Long Lin
A robust method based on reverse engineering was utilized to construct the ion-channel conductance functions for airway epithelial sodium channels (ENaC), the cystic fibrosis transmembrane conductance regulator (CFTR), and calcium-activated chloride channels (CaCC). The ion-channel conductance models for both normal (NL) and cystic fibrosis (CF) airway epithelia were developed and then coupled to an adenosine triphosphate (ATP) metabolism model and a fluid transport model (collectively called the integrated cell model) to investigate airway surface liquid (ASL) volume regulation and hence mucus concentration, by mechanical forces in NL and CF human airways...
November 15, 2017: Journal of Theoretical Biology
https://www.readbyqxmd.com/read/29153987/development-and-characterization-of-a-human-and-mouse-intestinal-epithelial-cell-monolayer-platform
#13
Kenji Kozuka, Ying He, Samantha Koo-McCoy, Padmapriya Kumaraswamy, Baoming Nie, Karen Shaw, Priscilla Chan, Michael Leadbetter, Limin He, Jason G Lewis, Ziyang Zhong, Dominique Charmot, Marwan Balaa, Andrew J King, Jeremy S Caldwell, Matthew Siegel
We describe the development and characterization of a mouse and human epithelial cell monolayer platform of the small and large intestines, with a broad range of potential applications including the discovery and development of minimally systemic drug candidates. Culture conditions for each intestinal segment were optimized by correlating monolayer global gene expression with the corresponding tissue segment. The monolayers polarized, formed tight junctions, and contained a diversity of intestinal epithelial cell lineages...
November 7, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/29144530/liddle-s-syndrome-in-an-african-male-due-to-a-novel-frameshift-mutation-in-the-beta-subunit-of-the-epithelial-sodium-channel-gene
#14
Robert Freercks, Surita Meldau, Erika Jones, Jason Ensor, Clarise Weimers-Willard, Brian Rayner
Resistant hypertension is a common clinical problem in South Africa and is frequently associated with low renin and aldosterone levels, especially in black Africans. In South Africa, novel variants in the epithelial sodium channel (ENaC) have been described to be associated with varying degrees of hypokalaemia and hypertension due to primary sodium retention. We report here a case of Liddle's syndrome due to a novel c.1709del11 (p.Ser570Tyrfs*20) deletion in the beta-subunit of the ENaC in a young black African male...
September 23, 2017: Cardiovascular Journal of Africa
https://www.readbyqxmd.com/read/29137360/novel-mechanisms-for-crotonaldehyde-induced-lung-edema
#15
Yue Li, Jianjun Chang, Yong Cui, Runzhen Zhao, Yan Ding, Yapeng Hou, Zhiyu Zhou, Hong-Long Ji, Hongguang Nie
Background: Crotonaldehyde is a highly noxious α,β-unsaturated aldehyde in cigarette smoke that causes edematous acute lung injury. Objective: To understand how crotonaldehyde impairs lung function, we examined its effects on human epithelial sodium channels (ENaC), which are major contributors to alveolar fluid clearance. Methods: We studied alveolar fluid clearance in C57 mice and ENaC activity was examined in H441 cells. Expression of α- and γ-ENaC was measured at protein and mRNA levels by western blot and real-time PCR, respectively...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29131643/electrophysiology-of-epithelial-sodium-channel-enac-embedded-in-supported-lipid-bilayer-using-a-single-nanopore-chip
#16
Muhammad Shuja Khan, Noura Sayed Dosoky, Ghulam Mustafa, Darayas Patel, Bakhrom K Berdiev, John Dalton Williams
Nanopore-based technologies are highly adaptable supports for developing label-free sensor chips to characterize lipid bilayers, membrane proteins and nucleotides. We utilized a single nanopore chip to study electrophysiology of epithelial Na+ channel (ENaC) incorporated in supported lipid membrane (SLM). An isolated nanopore was developed inside the silicon cavity followed by fusing large unilamellar vesicles (LUVs) of DPPS (1,2-dipalmitoyl-sn-glycero-3-phosphoserine) and DPPE (1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine) to produce a solvent-free SLM with giga-ohm (GΩ) sealed impedance...
November 13, 2017: Langmuir: the ACS Journal of Surfaces and Colloids
https://www.readbyqxmd.com/read/29129584/high-salt-loading-induces-urinary-storage-dysfunction-via-upregulation-of-epithelial-sodium-channel-alpha-in-the-bladder-epithelium-in-dahl-salt-sensitive-rats
#17
Seiji Yamamoto, Yuji Hotta, Kotomi Maeda, Tomoya Kataoka, Yasuhiro Maeda, Takashi Hamakawa, Yasuhiro Shibata, Shoichi Sasaki, Shinya Ugawa, Takahiro Yasui, Kazunori Kimura
We aimed to investigate whether high salt intake affects bladder function via epithelial sodium channel (ENaC) by using Dahl salt-resistant (DR) and salt-sensitive (DS) rats. Bladder weight of DR + high-salt diet (HS, 8% NaCl) and DS + HS groups were significantly higher than those of DR + normal-salt diet (NS, 0.3% NaCl) and DS + NS groups after one week treatment. We thereafter used only DR + HS and DS + HS group. Systolic and diastolic blood pressures were significantly higher in DS + HS group than in DR + HS group after the treatment period...
October 10, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/29126194/central-and-peripheral-slow-pressor-mechanisms-contributing-to
#18
Jiao Lu, Hong-Wei Wang, Monir Ahmad, Marzieh Keshtkar-Jahromi, Mordecai P Blaustein, John Hamlyn, Frans H H Leenen
Aims: High salt intake markedly enhances hypertension induced by angiotensin II (Ang II). We explored central and peripheral slow-pressor mechanisms which may be activated by Ang II and salt. Methods and Results: In Protocol I, Wistar rats were infused subcutaneously with low- dose Ang II (150 ng/kg/min) and fed regular (0.4%) or high salt (2%) diet for 14 days. In Protocol II, Ang II -high salt was combined with intracerebroventricular infusion of mineralocorticoid receptor (MR) blockers (eplerenone, spironolactone), epithelial sodium channel (ENaC) blocker (benzamil), angiotensin II type 1 receptor (AT1R) blocker (losartan) or vehicles...
November 8, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/29123030/the-nonproton-ligand-of-acid-sensing-ion-channel-3-activates-mollusk-specific-fanac-channels-via-a-mechanism-independent-of-native-fmrfamide-peptide
#19
Xiao-Na Yang, You-Ya Niu, Yan Liu, Yang Yang, Wang Jin, Xiao-Yang Cheng, Hong Liang, Heng-Shan Wang, You-Min Hu, Xiang-Yang Lu, Michael X Zhu, Tian-Le Xu, Yun Tian, Ye Yu
The degenerin/epithelial sodium channel (DEG/ENaC) superfamily of ion channels contains subfamilies with diverse functions that are fundamental to many physiological and pathological processes, ranging from synaptic transmission to epileptogenesis. The absence in mammals of some DEG/ENaCs subfamily orthologs such as FMRFamide peptide-activated sodium channels (FaNaCs), which have been identified only in mollusks, indicates that the various subfamilies diverged early in evolution. We recently reported that the nonproton agonist 2-guanidine-4-methylquinazoline (GMQ) activates acid-sensing ion channels (ASICs), a DEG/ENaC subfamily mainly in mammals, in the absence of acidosis...
November 9, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29107074/loss-of-%C3%AE-epithelial-sodium-channel-function-in-meibomian-glands-produces-pseudohypoaldosteronism-1-like-ocular-disease-in-mice
#20
Dongfang Yu, Yogesh Saini, Gang Chen, Andrew J Ghio, Hong Dang, Kimberlie A Burns, Yang Wang, Richard M Davis, Scott H Randell, Charles R Esther, Friedrich Paulsen, Richard C Boucher
Human subjects with pseudohypoaldosteronism-1 due to loss of function mutations in epithelial Na(+) channel (ENaC) subunits exhibit meibomian gland (MG) dysfunction. A conditional βENaC MG knockout mouse model was generated to elucidate the pathogenesis of absent ENaC function in the MG and associated ocular surface disease. βENaC MG KO mice exhibited a striking age dependent, female predominant MG dysfunction phenotype, with white toothpaste-like secretions observed obstructing MG orifices at seven weeks of age...
October 26, 2017: American Journal of Pathology
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