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Epithelial sodium channel

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
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
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
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
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
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
Steven J St John
Three experiments assessed potential changes in the rat's perception of sodium chloride (NaCl) during a state of sodium appetite. In Experiment 1, sodium-sufficient rats licking a range of NaCl concentrations (0.028-0.89M) in 15s trials showed an inverted U-shaped concentration response function peaking at 0.281M. Depleted rats (furosemide) showed an identical function, merely elevated, suggesting altered qualitative or hedonic perception but no change in perceived intensity. In Experiment 2, sodium-depleted rats were tested with NaCl, sodium gluconate, and potassium chloride (KCl; 0...
September 22, 2016: Chemical Senses
Shuji Shimizu, Tsuyoshi Akiyama, Toru Kawada, Yusuke Sata, Michael James Turner, Masafumi Fukumitsu, Hiromi Yamamoto, Atsunori Kamiya, Toshiaki Shishido, Masaru Sugimachi
This study examined the mechanism of release of endogenous acetylcholine (ACh) in rabbit renal cortex by applying a microdialysis technique. In anesthetized rabbits, a microdialysis probe was implanted into the renal cortex and perfused with Ringer's solution containing high potassium concentration, high sodium concentration, a Na(+)/K(+)-ATPase inhibitor (ouabain), or an epithelial Na(+) channel blocker (benzamil). Dialysate samples were collected at baseline and during exposure to each agent, and ACh concentrations in the samples were measured by high-performance liquid chromatography...
September 22, 2016: Journal of Physiological Sciences: JPS
Rudolf Lucas, Qiang Yue, Abdel Alli, Billie Jeanne Duke, Otor Al-Khalili, Tiffany L Thai, Jürg Hamacher, Supriya Sridhar, Iryna Lebedyeva, Huabo Su, Susan Tzotzos, Bernhard Fischer, Armanda Formigoa Gameiro, Maria Loose, Trinad Chakraborty, Waheed Shabbir, Mohammed Aufy, Rosa Lemmens-Gruber, Douglas C Eaton, Istvan Czikora
Regulation of the epithelial sodium channel (ENaC), which regulates fluid homeostasis and blood pressure, is complex and remains incompletely understood. The TIP peptide, a mimic of the lectin-like domain of TNF, activates ENaC, by binding to glycosylated residues in the extracellular loop of ENaC-α, as well as to a hitherto uncharacterized internal site. Molecular docking studies suggested three residues - Val567, Glu568 and Glu571 - located at the interface between the second transmembrane and carboxy-terminal domains of ENaC-α, as a critical site for binding of the TIP peptide...
September 19, 2016: Journal of Biological Chemistry
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
X Liu, R S Edinger, C A Klemens, Y L Phua, A J Bodnar, W A LaFramboise, J Ho, M B Butterworth
The epithelial sodium channel (ENaC) is expressed in the epithelial cells of the distal convoluted tubules, connecting tubules and cortical collecting duct (CCD) in the kidney nephron. Under the regulation of the steroid hormone aldosterone, ENaC is a major determinant of sodium (Na(+) ) and water balance. The ability of aldosterone to regulate microRNAs (miRs) in the kidney has recently been realized, but the role of miRs in Na(+) regulation has not been well established. Here we demonstrate that expression of a miR cluster mmu-miR-23∼24∼27, is upregulated in the CCD by aldosterone stimulation both in vitro and in vivo...
September 16, 2016: Journal of Cellular Physiology
Wei-Wan Zheng, Xin-Yuan Li, Hui-Bin Liu, Zi-Rui Wang, Qing-Qing Hu, Yu-Xia Li, Bin-Lin Song, Jie Lou, Qiu-Shi Wang, He-Ping Ma, Zhi-Ren Zhang
Recent studies suggest that the epithelial sodium channel (ENaC) is expressed in the endothelial cells. To test whether high salt affects the NO production via regulation of endothelial ENaC, human umbilical vein endothelial cells (HUVECs) were incubated in solutions containing either normal or high sodium (additional 20 mM NaCl). Our data showed that high sodium treatment significantly increased α-, β-, and γ-ENaC expression levels in HUVECs. Using the cell-attached patch-clamp technique, we demonstrated that high sodium treatment significantly increased ENaC open probability (P O )...
2016: Oxidative Medicine and Cellular Longevity
Verena Rickert-Zacharias, Carsten Schultz, Marcus A Mall
No abstract text is available yet for this article.
September 15, 2016: American Journal of Respiratory and Critical Care Medicine
Reinhold G Erben, Olena Andrukhova
Fibroblast growth factor-23 (FGF23) is a bone-derived hormone protecting against the potentially deleterious effects of hyperphosphatemia by suppression of phosphate reabsorption and of active vitamin D hormone synthesis in the kidney. The kidney is one of the main target organs of FGF23 signaling. The purpose of this review is to highlight the recent advances in the area of FGF23-Klotho signaling in the kidney. During recent years, it has become clear that FGF23 acts independently on proximal and distal tubular epithelium...
September 10, 2016: Bone
Lukas Klumpp, Efe C Sezgin, Franziska Eckert, Stephan M Huber
Breast cancer, lung cancer and melanoma exhibit a high metastatic tropism to the brain. Development of brain metastases severely worsens the prognosis of cancer patients and constrains curative treatment options. Metastasizing to the brain by cancer cells can be dissected in consecutive processes including epithelial-mesenchymal transition, evasion from the primary tumor, intravasation and circulation in the blood, extravasation across the blood-brain barrier, formation of metastatic niches, and colonization in the brain...
2016: International Journal of Molecular Sciences
Sudhirkumar Yanpallewar, Ting Wang, Dawn C I Koh, Eros Quarta, Gianluca Fulgenzi, Lino Tessarollo
Nedd4-2 (NEDD4L in humans) is a ubiquitin protein ligase best known for its role in regulating ion channel internalization and turnover. Nedd4-2 deletion in mice causes perinatal lethality associated with increased epithelial sodium channel (ENaC) expression in lung and kidney. Abundant data suggest that Nedd4-2 plays a role in neuronal functions and may be linked to epilepsy and dyslexia in humans. We used a mouse model of Nedd4-2 haploinsufficiency to investigate whether an alteration in Nedd4-2 levels of expression affects general nervous system functions...
2016: Scientific Reports
Luciana C Veiras, Jiyang Han, Donna L Ralph, Alicia A McDonough
Angiotensin II (AngII) hypertension increases distal tubule Na-Cl cotransporter (NCC) abundance and phosphorylation (NCCp), as well as epithelial Na(+) channel abundance and activating cleavage. Acutely raising plasma [K(+)] by infusion or ingestion provokes a rapid decrease in NCCp that drives a compensatory kaliuresis. The first aim tested whether acutely raising plasma [K(+)] with a single 3-hour 2% potassium meal would lower NCCp in Sprague-Dawley rats after 14 days of AngII (400 ng/kg per minute). The potassium-rich meal neither decreased NCCp nor increased K(+) excretion...
October 2016: Hypertension
Adrián Galiana-Simal, Elena Olivares-Álvaro, Mercedes Klett-Mingo, María Belén Ruiz-Roso, Sandra Ballesteros, Natalia de Las Heras, Peter J Fuller, Vicente Lahera, Beatriz Martín-Fernández
Aldosterone plays a central role in the development of cardiac pathological states involving ion transport imbalances, especially sodium transport. We have previously demonstrated a cardioprotective effect of proanthocyanidins in aldosterone-treated rats. Our objective was to investigate for the first time the effect of proanthocyanidins on serum and glucocorticoid-regulated kinase 1 (SGK1), epithelial Na(+) channel (γ-ENaC), neuronal precursor cells expressed developmentally down-regulated 4-2 (Nedd4-2) and phosphoNedd4-2 protein expression in the hearts of aldosterone-treated rats...
August 14, 2016: Journal of Nutritional Biochemistry
Israel Hanukoglu
The acid-sensing ion channels (ASICs) and epithelial sodium channels (ENaC) are members of a superfamily of channels that play critical roles in mechanosensation, chemosensation, nociception, and regulation of blood volume and pressure. These channels look and function like a tripartite funnel that directs the flow of Na(+) ions into the cytoplasm via the channel pore in the membrane. The subunits that form these channels share a common structure with two transmembrane segments (TM1 and TM2) and a large extracellular part...
August 31, 2016: FEBS Journal
Song-Yan Hu, Xiao-Dong Jin, Hao Zhang, Jun Chen, Guo-Zhu Yang, Xiao-Dong Wang, Lu Tang, Xing-Yan Lu, Li Lu, Qing-Nan Li
OBJECTIVE: To explore the role of epithelial sodium channel (ENaC) in regulating the functional activity of osteoclasts. METHODS: Multinucleated osteoclasts were obtained by inducing the differentiation of rat bone marrow cells with macrophage colony-stimulating factor (M-CSF) and RANKL. The osteoclasts were exposed to different concentrations of the ENaC inhibitor amiloride, and the expression of ENaC on osteoclasts was examined using immunofluorescence technique...
August 20, 2016: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
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