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https://www.readbyqxmd.com/read/28108847/airway-mucus-inflammation-and-remodeling-emerging-links-in-the-pathogenesis-of-chronic-lung-diseases
#1
REVIEW
Zhe Zhou-Suckow, Julia Duerr, Matthias Hagner, Raman Agrawal, Marcus A Mall
Airway mucus obstruction is a hallmark of many chronic lung diseases including rare genetic disorders such as cystic fibrosis (CF) and primary ciliary dyskinesia, as well as common lung diseases such as asthma and chronic obstructive pulmonary disease (COPD), which have emerged as a leading cause of morbidity and mortality worldwide. However, the role of excess airway mucus in the in vivo pathogenesis of these diseases remains poorly understood. The generation of mice with airway-specific overexpression of epithelial Na(+) channels (ENaC), exhibiting airway surface dehydration (mucus hyperconcentration), impaired mucociliary clearance (MCC) and mucus plugging, led to a model of muco-obstructive lung disease that shares key features of CF and COPD...
January 20, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/28087701/the-ubiquitin-ligase-nedd4l-regulates-the-na-k-2cl-co-transporter-nkcc1-slc12a2-in-the-colon
#2
Chong Jiang, Hiroshi Kawabe, Daniela Rotin
The ubiquitin ligase Nedd4-like (Nedd4L, or Nedd4-2) binds to and regulates stability of the epithelial Na+ channel (ENaC) in salt absorbing epithelia in the kidney, lung, and other tissues. Its role in the distal colon, which also absorbs salt and fluid and expresses ENaC, is unknown. Using conditional knockout approach to knockout Nedd4L in mice intestinal epithelium (Nedd4Lf/f;Vil-CreERT2) we show here that Nedd4L depletion leads to a higher steady-state short circuit current (Isc) in mouse distal colon tissue relative to controls...
January 13, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28086951/sodium-glucose-transporter-2-sglt2-inhibition-with-empagliflozin-improves-cardiac-diastolic-function-in-a-female-rodent-model-of-diabetes
#3
Javad Habibi, Annayya R Aroor, James R Sowers, Guanghong Jia, Melvin R Hayden, Mona Garro, Brady Barron, Eric Mayoux, R Scott Rector, Adam Whaley-Connell, Vincent G DeMarco
Obese and diabetic individuals are at increased risk for impairments in diastolic relaxation and heart failure with preserved ejection fraction. The impairments in diastolic relaxation are especially pronounced in obese and diabetic women and predict future cardiovascular disease (CVD) events in this population. Recent clinical data suggest sodium glucose transporter-2 (SGLT2) inhibition reduces CVD events in diabetic individuals, but the mechanisms of this CVD protection are unknown. To determine whether targeting SGLT2 improves diastolic relaxation, we utilized empagliflozin (EMPA) in female db/db mice...
January 13, 2017: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/28062481/sex-specific-effects-of-sex-steroids-on-alveolar-epithelial-na-transport
#4
Melanie Haase, Mandy Laube, Ulrich H Thome
Alveolar fluid clearance mediates perinatal lung transition to air breathing in newborn infants, which is accomplished by epithelial Na+ channels (ENaC) and the Na,K-ATPase. Male sex represents a major risk factor for developing respiratory distress, especially in preterm infants. We previously showed that male sex is associated with reduced epithelial Na+ transport, possibly contributing to the sexual dimorphism in newborn respiratory distress. This study aimed to determine sex-specific effects of sex steroids on epithelial Na+ transport...
January 6, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28052878/high-frequency-of-variants-of-candidate-genes-in-black-africans-with-low-renin-resistant-hypertension
#5
Erika S Jones, J David Spence, Adam D Mcintyre, Justus Nondi, Kennedy Gogo, Adeseye Akintunde, Daniel G Hackam, Brian L Rayner
OBJECTIVES: Black subjects tend to retain salt and water, be more sensitive to aldosterone, and have suppression of plasma renin activity. Variants of the renal sodium channel (ENaC, SCNN1B) account for approximately 6% of resistant hypertension (RHT) in Blacks; other candidate genes may be important. METHODS: Six candidate genes associated with low renin-resistant hypertension were sequenced in Black Africans from clinics in Kenya and South Africa. CYP11B2 was sequenced if the aldosterone level was high (primary aldosteronism phenotype); SCNN1B, NEDD4L, GRK4, UMOD, and NPPA genes were sequenced if the aldosterone level was low (Liddle phenotype)...
January 4, 2017: American Journal of Hypertension
https://www.readbyqxmd.com/read/28024413/ferulic-acid-induces-proliferation-and-differentiation-of-rat-osteoblasts-in-vitro-through-cgmp-pkgii-enac-signaling
#6
Jian-Lin Gao, Jun Chen, Guo-Zhu Yang, Li Lu, Xing-Yan Lu, Huan-Huan Jia, Xiao-Dong Jin, Hao Zhang, Qing-Nan Li
Ferulic acid (FA) is an active component of the traditional Chinese herb Angelica sinensis. Numerous health benefits have been attributed to FA, but few studies have investigated the effects of FA on osteoblasts (Obs). Our work studied the effects of FA on proliferation, differentiation, and mineralization of rat calvarial Obs and examined the signaling pathways involved. Cell proliferation and differentiation were evaluated by Cell Counting Kit-8 (CCK-8) and alkaline phosphatase (ALP) assay kit, respectively...
December 27, 2016: Journal of Asian Natural Products Research
https://www.readbyqxmd.com/read/28017617/mir-263a-regulates-enac-to-maintain-osmotic-and-intestinal-stem-cell-homeostasis-in-drosophila
#7
Kevin Kim, Ruei-Jiun Hung, Norbert Perrimon
Proper regulation of osmotic balance and response to tissue damage is crucial in maintaining intestinal stem cell (ISC) homeostasis. We found that Drosophila miR-263a downregulates the expression of epithelial sodium channel (ENaC) subunits in enterocytes (ECs) to maintain osmotic and ISC homeostasis. In the absence of miR-263a, the intraluminal surface of the intestine displays dehydration-like phenotypes, Na(+) levels are increased in ECs, stress pathways are activated in ECs, and ISCs overproliferate. Furthermore, miR-263a mutants have increased bacterial load and expression of antimicrobial peptides...
January 9, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28003189/involvement-of-enac-in-the-development-of-salt-sensitive-hypertension
#8
Tengis S Pavlov, Alexander Staruschenko
Salt-sensitive hypertension is associated with renal and vascular dysfunctions which lead to impaired fluid excretion, increased cardiac output and total peripheral resistance. It is commonly accepted that increased renal sodium handling and plasma volume expansion are necessary factors for the development of salt-induced hypertension. The epithelial sodium channel (ENaC) is a trimeric ion channel expressed in the distal nephron which plays a critical role in the regulation of sodium reabsorption in both normal and pathological conditions...
December 21, 2016: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/27992235/effects-of-baicalin-on-alveolar-fluid-clearance-and-%C3%AE-enac-expression-in-rats-with-lps-induced-acute-lung-injury
#9
Jia Deng, Dao-Xin Wang, Ai-Ling Liang, Jing Tang, Da-Kai Xiang
Baicalin has been reported to attenuate lung edema in the process of lung injury. However, the effect of baicalin on alveolar fluid clearance (AFC) and epithelial sodium channel (ENaC) expression has not been tested. Sprague-Dawley rats were anesthetized and intratracheally injected with either 1 mg/kg lipopolysaccharide (LPS) or saline vehicle. Baicalin with various concentrations (10, 50, and 100 mg/kg) was injected intraperitoneally 30 min before administration of LPS. Then lungs were isolated for measurement of AFC, cyclic adenosine monophosphate (cAMP) level, and cellular localization of α-ENaC...
August 31, 2016: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/27941075/%C3%AE-%C3%AE-%C3%AE-enac-is-inhibited-by-cftr-but-stimulated-by-camp-in-xenopus-laevis-oocytes
#10
Robert Rauh, Christian Hoerner, Christoph Korbmacher
The epithelial sodium channel (ENaC) and the CFTR chloride channel critically regulate airway surface liquid by driving fluid absorption and secretion, respectively. Their functional interplay is complex and incompletely understood. ENaC is a heteromeric channel with three well characterised subunits (α, β, γ). In humans, an additional δENaC subunit exists in lung and several other tissues where it may replace the α-subunit to form δβγENaC. Little is known about the physiological role of δβγENaC and its possible interaction with CFTR...
December 9, 2016: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/27932503/computational-modelling-of-epithelial-fluid-and-ion-transport-in-the-parotid-duct-after-transfection-of-human-aquaporin-1
#11
Shelley Fong, John A Chiorini, James Sneyd, Vinod Suresh
Previous studies have shown that localized delivery of the aquaporin-1 (AQP1) gene to the parotid duct can restore saliva flow in minipigs following irradiation-induced salivary hypofunction. The resulting flow rate and electrochemisty of secreted saliva contradicts current understanding of ductal fluid transport. We hypothesized that changes in expression of ion transport proteins have occurred following AQP1 transfection. We use a mathematical model of ion and fluid transport across the parotid duct epithelial cells to predict the expression profile of ion transporters that are consistent with the experimental measurements of saliva composition and secretion rates...
December 8, 2016: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/27903760/interactions-between-intersubunit-transmembrane-domains-regulate-the-chaperone-dependent-degradation-of-an-oligomeric-membrane-protein
#12
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
#13
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/27895120/ankyrin-g-expression-regulates-apical-delivery-of-the-epithelial-sodium-channel-enac
#14
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 cells. However, the mechanisms underlying AnkG regulation of Na(+) transport were unknown. Here we report that AnkG expression directly regulates Na(+) transport by altering ENaC activity in the apical membrane...
January 6, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27867979/na-homeostasis-by-epithelial-na-channel-enac-and-nax-channel-nax-cooperation-of-enac-and-nax
#15
EDITORIAL
Yoshinori Marunaka, Rie Marunaka, Hongxin Sun, Toshiro Yamamoto, Narisato Kanamura, Akiyuki Taruno
No abstract text is available yet for this article.
October 2016: Annals of Translational Medicine
https://www.readbyqxmd.com/read/27835672/the-expression-of-water-and-ion-channels-in-diffuse-alveolar-damage-is-not-dependent-on-dad-etiology
#16
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/27833542/adaptive-automation-triggered-by-eeg-based-mental-workload-index-a-passive-brain-computer-interface-application-in-realistic-air-traffic-control-environment
#17
Pietro Aricò, Gianluca Borghini, Gianluca Di Flumeri, Alfredo Colosimo, Stefano Bonelli, Alessia Golfetti, Simone Pozzi, Jean-Paul Imbert, Géraud Granger, Raïlane Benhacene, Fabio Babiloni
Adaptive Automation (AA) is a promising approach to keep the task workload demand within appropriate levels in order to avoid both the under- and over-load conditions, hence enhancing the overall performance and safety of the human-machine system. The main issue on the use of AA is how to trigger the AA solutions without affecting the operative task. In this regard, passive Brain-Computer Interface (pBCI) systems are a good candidate to activate automation, since they are able to gather information about the covert behavior (e...
2016: Frontiers in Human Neuroscience
https://www.readbyqxmd.com/read/27830759/marked-increases-in-mucociliary-clearance-produced-by-synergistic-secretory-agonists-or-inhibition-of-the-epithelial-sodium-channel
#18
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/27825168/activation-of-sgk1-in-endometrial-epithelial-cells-in-response-to-pi3k-akt-inhibition-impairs-embryo-implantation
#19
Madhuri S Salker, Jennifer H Steel, Zohreh Hosseinzadeh, Jaya Nautiyal, Zoe Webster, Yogesh Singh, Sara Brucker, Florian Lang, Jan J Brosens
BACKGROUND: Serum & Glucocorticoid Regulated Kinase 1 (SGK1) plays a fundamental role in ion and solute transport processes in epithelia. In the endometrium, down-regulation of SGK1 during the window of receptivity facilitates embryo implantation whereas expression of a constitutively active mutant in the murine uterus blocks implantation. METHODS/RESULTS: Here, we report that treatment of endometrial epithelial cells with specific inhibitors of the phosphoinositide 3-kinase (PI3K)/AKT activity pathway results in reciprocal activation of SGK1...
2016: Cellular Physiology and Biochemistry
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
#20
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
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