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Epithelial sodium channel

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https://www.readbyqxmd.com/read/28646163/aldosterone-modulates-the-association-between-ncc-and-enac
#1
Brandi M Wynne, Abinash C Mistry, Otor Al-Khalili, Rickta Mallick, Franziska Theilig, Douglas C Eaton, Robert S Hoover
Distal sodium transport is a final step in the regulation of blood pressure. As such, understanding how the two main sodium transport proteins, the thiazide-sensitive sodium chloride cotransporter (NCC) and the epithelial sodium channel (ENaC), are regulated is paramount. Both are expressed in the late distal nephron; however, no evidence has suggested that these two sodium transport proteins interact. Recently, we established that these two sodium transport proteins functionally interact in the second part of the distal nephron (DCT2)...
June 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28633068/multi-electrode-system-for-measurement-of-transmembrane-ion-fluxes-through-living-epithelial-cells
#2
Mirosław Zając, Andrzej Lewenstam, Krzysztof Dolowy
Cystic Fibrosis (CF) is the most common fatal human genetic disease. It is caused by the defect in a single anion channel protein which affects ion and water transport across the epithelial tissue. A flat multi-electrode platform of diameter 12mm, allowing for measurement of four ions: sodium, potassium, hydrogen and chloride by exchangeable/replaceable ion-selective electrodes is described. The measurement is possible owing to the architecture of the platform which accommodates all the electrodes and inlets/outlets...
June 13, 2017: Bioelectrochemistry
https://www.readbyqxmd.com/read/28614116/parathyroid-hormone-and-the-regulation-of-renal-tubular-calcium-transport
#3
Benjamin Ko
PURPOSE OF REVIEW: Renal tubule excretion of calcium is carefully and complexly regulated. At the center of this process, parathyroid hormone (PTH) is the chief regulator of renal calcium reabsorption. This review outlines our current understanding of PTH's effects on renal tubular calcium transport, focusing on the more recent discoveries beyond its direct regulation of epithelial Ca channel transient receptor potential vanilloid 5 (TRPV5) and looking at its interaction with sodium transport and the hormones fibroblast growth factor 23 (FGF23) and klotho...
June 12, 2017: Current Opinion in Nephrology and Hypertension
https://www.readbyqxmd.com/read/28613240/an-isoform-of-nedd4-2-plays-a-pivotal-role-in-electrophysiological-cardiac-abnormalities
#4
Shintaro Minegishi, Tomoaki Ishigami, Hisho Kawamura, Tabito Kino, Lin Chen, Rie Nakashima-Sasaki, Hiroshi Doi, Kengo Azushima, Hiromichi Wakui, Yumi Chiba, Kouichi Tamura
We have previously shown that neural precursor cell-expressed developmentally downregulated gene 4-2 (Nedd4-2) isoforms with a C2 domain are closely related to ubiquitination of epithelial sodium channel (ENaC), resulting in salt-sensitive hypertension by Nedd4-2 C2 targeting in mice. The sodium voltage-gated channel alpha subunit 5 (SCN5A) gene encodes the α subunit of the human cardiac voltage-gated sodium channel (I Na), and the potassium voltage-gated channel subfamily H member 2 (KCNH2) gene encodes rapidly activating delayed rectifier K channels (I Kr)...
June 14, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28611771/tnf-lectin-like-domain-restores-epithelial-sodium-channel-function-in-frameshift-mutants-associated-with-pseudohypoaldosteronism-type-1b
#5
Anita Willam, Mohammed Aufy, Susan Tzotzos, Dina El-Malazi, Franziska Poser, Alina Wagner, Birgit Unterköfler, Didja Gurmani, David Martan, Shahid Muhammad Iqbal, Bernhard Fischer, Hendrik Fischer, Helmut Pietschmann, Istvan Czikora, Rudolf Lucas, Rosa Lemmens-Gruber, Waheed Shabbir
Previous in vitro studies have indicated that tumor necrosis factor (TNF) activates amiloride-sensitive epithelial sodium channel (ENaC) current through its lectin-like (TIP) domain, since cyclic peptides mimicking the TIP domain (e.g., solnatide), showed ENaC-activating properties. In the current study, the effects of TNF and solnatide on individual ENaC subunits or ENaC carrying mutated glycosylation sites in the α-ENaC subunit were compared, revealing a similar mode of action for TNF and solnatide and corroborating the previous assumption that the lectin-like domain of TNF is the relevant molecular structure for ENaC activation...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28604611/eplerenone-resistant-salt-sensitive-hypertension-in-nedd4-2-c2-ko-mice
#6
Tabito Kino, Tomoaki Ishigami, Tsumugi Murata, Hiroshi Doi, Rie Nakashima-Sasaki, Lin Chen, Michiko Sugiyama, Kengo Azushima, Hiromichi Wakui, Shintaro Minegishi, Kouichi Tamura
The epithelial sodium channel (ENaC) plays critical roles in maintaining fluid and electrolyte homeostasis and is located in the aldosterone-sensitive distal nephron (ASDN). We previously found that Nedd4-2 C2 knockout (KO) mice showed salt-sensitive hypertension with paradoxically enhanced ENaC gene expression in ASDN under high oral salt intake. Eplerenone (EPL), a selective aldosterone blocker, is a promising therapeutic option for resistant or/and salt-sensitive hypertension. We examined the effect of EPL on Nedd4-2 C2 KO mice with respect to blood pressure, metabolic parameters, and molecular level changes in ASDN under high oral salt intake...
June 11, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28588583/hypercapnia-impairs-enac-cell-surface-stability-by-promoting-phosphorylation-polyubiquitination-and-endocytosis-of-%C3%AE-enac-in-a-human-alveolar-epithelial-cell-line
#7
Paulina Gwoździńska, Benno A Buchbinder, Konstantin Mayer, Susanne Herold, Rory E Morty, Werner Seeger, István Vadász
Acute lung injury is associated with formation of pulmonary edema leading to impaired gas exchange. Patients with acute respiratory distress syndrome (ARDS) require mechanical ventilation to improve oxygenation; however, the use of relatively low tidal volumes (to minimize further injury of the lung) often leads to further accumulation of carbon dioxide (hypercapnia). Hypercapnia has been shown to impair alveolar fluid clearance (AFC), thereby causing retention of pulmonary edema, and may lead to worse outcomes; however, the underlying molecular mechanisms remain incompletely understood...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28579836/update-on-the-renal-toxicity-of-iodinated-contrast-drugs-used-in-clinical-medicine
#8
REVIEW
Michele Andreucci, Teresa Faga, Raffaele Serra, Giovambattista De Sarro, Ashour Michael
An important side effect of diagnostic contrast drugs is contrast-induced acute kidney injury (CI-AKI; a sudden decrease in renal function) occurring 48-72 hours after injection of a contrast drug that cannot be attributed to other causes. Its existence has recently been challenged, because of some retrospective studies in which the incidence of AKI was not different between subjects who received a contrast drug and those who did not, even using propensity score matching to prevent selection bias. For some authors, only patients with estimated glomerular filtration rate <30 mL/min/1...
2017: Drug, Healthcare and Patient Safety
https://www.readbyqxmd.com/read/28566357/living-with-a-leaky-skin-upregulation-of-ion-transport-proteins-during-sloughing
#9
Nicholas C Wu, Rebecca L Cramp, Craig E Franklin
Amphibian skin is a multifunctional organ providing protection from the external environment and facilitating the physiological exchange of gases, water and salts with the environment. In order to maintain these functions, the outer layer of skin is regularly replaced in a process called sloughing. During sloughing, the outermost layer of the skin is removed in its entirety, which has the potential to interfere with skin permeability and ion transport, disrupting homeostasis. In this study, we measured, in vivo, the effects of sloughing on the cutaneous efflux of ions in toads Rhinella marina kept in freshwater conditions...
June 1, 2017: Journal of Experimental Biology
https://www.readbyqxmd.com/read/28562363/novel-mechanisms-for-crotonaldehyde-induced-lung-edema
#10
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...
May 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28559392/renal-dysfunction-induced-by-kidney-specific-gene-deletion-of-hsd11b2-as-a-primary-cause-of-salt-dependent-hypertension
#11
Kohei Ueda, Mitsuhiro Nishimoto, Daigoro Hirohama, Nobuhiro Ayuzawa, Wakako Kawarazaki, Atsushi Watanabe, Tatsuo Shimosawa, Johannes Loffing, Ming-Zhi Zhang, Takeshi Marumo, Toshiro Fujita
Genome-wide analysis of renal sodium-transporting system has identified specific variations of Mendelian hypertensive disorders, including HSD11B2 gene variants in apparent mineralocorticoid excess. However, these genetic variations in extrarenal tissue can be involved in developing hypertension, as demonstrated in former studies using global and brain-specific Hsd11b2 knockout rodents. To re-examine the importance of renal dysfunction on developing hypertension, we generated kidney-specific Hsd11b2 knockout mice...
May 30, 2017: Hypertension
https://www.readbyqxmd.com/read/28557567/gene-expression-of-the-concentration-sensitive-sodium-channel-is-suppressed-in-lipopolysaccharide-induced-acute-lung-injury-in-mice
#12
Teruki Hagiwara, Shigeru Yoshida, Yuji Hidaka
PURPOSE: The concentration-sensitive sodium channel (NaC) is expressed in alveolar type II epithelial cells and pulmonary microvascular endothelial cells in mouse lungs. We recently reported that NaC contributes to amiloride-insensitive sodium transport in mouse lungs (Respiratory Physiology & Neurobiology, 2016). However, details regarding its physiological role in the lung remain unknown. To examine whether NaC is involved in alveolar fluid clearance during an acute lung injury (ALI), we analyzed the relationship between NaC gene expression in the lung and the development of pulmonary edema in lipopolysaccharide (LPS)-induced ALI mice...
April 2017: Experimental Lung Research
https://www.readbyqxmd.com/read/28542554/sodium-tanshinone-iia-sulfonate-stimulated-cl-secretion-in-mouse-trachea
#13
Peng-Xiao Chen, Yi-Lin Zhang, Jia-Wen Xu, Ming-Hao Yu, Jie-Hong Huang, Lei Zhao, Wen-Liang Zhou
Sodium tanshinone IIA sulfonate (STS) is a derivate of tanshinone IIA, a lipophilic compound in Salvia miltiorrhiza. This study aimed to investigate the effect of STS on ion transport in mouse tracheal epithelium and the mechanisms underlying it. Short-circuit current (Isc) was measured to evaluate the effect of STS on transepithelial ion transport. Intracellular Ca2+ imaging was performed to observe intracellular Ca2+ concentration ([Ca2+]i) changes induced by STS in primary cultured mouse tracheal epithelial cells...
2017: PloS One
https://www.readbyqxmd.com/read/28539224/inhaled-enac-antisense-oligonucleotide-ameliorates-cystic-fibrosis-like-lung-disease-in-mice
#14
Jeff R Crosby, Chenguang Zhao, Chong Jiang, Dong Bai, Melanie Katz, Sarah Greenlee, Hiroshi Kawabe, Michael McCaleb, Daniela Rotin, Shuling Guo, Brett P Monia
BACKGROUND: Epithelial sodium channel (ENaC, Scnn1) hyperactivity in the lung leads to airway surface dehydration and mucus accumulation in cystic fibrosis (CF) patients and in mice with CF-like lung disease. METHODS: We identified several potent ENaC specific antisense oligonucleotides (ASOs) and tested them by inhalation in mouse models of CF-like lung disease. RESULTS: The inhaled ASOs distributed into lung airway epithelial cells and decreased ENaC expression by inducing RNase H1-dependent degradation of the targeted Scnn1a mRNA...
May 20, 2017: Journal of Cystic Fibrosis: Official Journal of the European Cystic Fibrosis Society
https://www.readbyqxmd.com/read/28528375/hypothalamic-signaling-in-body-fluid-homeostasis-and-hypertension
#15
REVIEW
Brian J Kinsman, Haley N Nation, Sean D Stocker
PURPOSE OF REVIEW: The central nervous system plays a pivotal role in the regulation of extracellular fluid volume and consequently arterial blood pressure. Key hypothalamic regions sense and integrate neurohumoral signals to subsequently alter intake (thirst and salt appetite) and output (renal excretion via neuroendocrine and autonomic function). Here, we review recent findings that provide new insight into such mechanisms that may represent new therapeutic targets. RECENT FINDINGS: Implementation of cutting edge neuroscience approaches such as opto- and chemogenetics highlight pivotal roles of circumventricular organs to impact body fluid homeostasis...
June 2017: Current Hypertension Reports
https://www.readbyqxmd.com/read/28484659/systemic-pseudohypoaldosteronism-type-i-a-case-report-and-review-of-the-literature
#16
Nasifa Nur, Cameron Lang, Juanita K Hodax, Jose Bernardo Quintos
Systemic pseudohypoaldosteronism (PHA) type I is a rare genetic disorder resulting from mutations in the subunits of the epithelial sodium channel that manifests as severe salt wasting, hyperkalemia, and metabolic acidosis in infancy. In this article we report a patient with systemic PHA type I presenting with severe dehydration due to salt wasting at 6 days of life. She was found to have a known mutation in the SCNN1A gene and subsequently required treatment with sodium supplementation. We also review the clinical presentation, differential diagnosis, and treatment of systemic PHA type I and summarize data from 27 cases with follow-up data...
2017: Case Reports in Pediatrics
https://www.readbyqxmd.com/read/28481660/spx-101-is-a-novel-enac-targeted-therapeutic-for-cystic-fibrosis-that-restores-mucus-transport
#17
David W Scott, Matthew P Walker, Juliana Sesma, Bryant Wu, Timothy J Stuhlmiller, Juan R Sabater, William M Abraham, Timothy M Crowder, Dale J Christensen, Robert Tarran
RATIONALE: Cystic Fibrosis lung disease (CF) is caused by the loss of function of the cystic fibrosis transmembrane conductance regulator (CFTR) combined with hyperactivation of the epithelial sodium channel (ENaC). In the lung, ENaC is responsible for movement of sodium which creates an osmotic gradient that pulls fluid out of the airway. Hyperactivation of ENaC contributes to reduced airway hydration causing mucus dehydration, decreased mucociliary clearance, and chronic bacterial infections...
May 8, 2017: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/28480509/oxidized-low-density-lipoprotein-stimulates-epithelial-sodium-channels-in-endothelial-cells-of-mouse-thoracic-aorta
#18
Chen Liang, Qiu-Shi Wang, Xu Yang, Na Niu, Qing-Qing Hu, Bao-Long Zhang, Ming-Ming Wu, Chang-Jiang Yu, Xiao Chen, Bin-Lin Song, Zhi-Ren Zhang, He-Ping Ma
BACKGROUND AND PURPOSE: Epithelial sodium channel (ENaC) is expressed in endothelial cells and acts as a negative modulator of vasodilation. Oxidized low-density lipoprotein (ox-LDL) is a key pathological factor in endothelial dysfunction. The present study is to examine the role of ENaC in ox-LDL-induced endothelial dysfunction and its associated signal transduction pathway. EXPERIMENTAL APPROACH: Patch-clamp techniques combined with pharmacological approaches were used to examine ENaC activity in the endothelial cells of split-open mouse thoracic aorta...
May 8, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28473772/lack-of-effects-of-metformin-and-aicar-chronic-infusion-on-the-development-of-hypertension-in-dahl-salt-sensitive-rats
#19
Tengis S Pavlov, Vladislav Levchenko, Daria V Ilatovskaya, Hui Li, Oleg Palygin, Nuria M Pastor-Soler, Kenneth R Hallows, Alexander Staruschenko
In the kidney, reabsorption via the epithelial sodium channel (ENaC) is involved in long-term blood pressure control. Previously we demonstrated that ENaC hyperactivity is associated with development of salt-sensitive (SS) hypertension in Dahl SS rats. AMP-activated kinase (AMPK), playing a role in cellular energy homeostasis, has been shown to decrease ENaC activity. Here, we tested whether metformin and AICAR, two drugs that activate AMPK, affect the development of salt-induced hypertension. High salt diet significantly increased mean arterial pressure (MAP) in Dahl SS rats...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28468944/enac-activity-is-regulated-by-calpain-2-proteolysis-of-marcks-proteins
#20
Darrice S Montgomery, Ling Yu, Zinah M Ghazi, Tiffany L Thai, Otor Al-Khalili, He-Ping Ma, Douglas C Eaton, Abdel A Alli
We previously demonstrated a role for the myristoylated alanine-rich C kinase substrate (MARCKS) to serve as an adaptor protein in the anionic phospholipid phosphate-dependent regulation of the epithelial sodium channel (ENaC). Both MARCKS and ENaC are regulated by proteolysis. Calpains are a family of ubiquitously expressed intracellular Ca(2+)-dependent cysteine proteases involved in signal transduction. Here we examine the role of calpain-2 in regulating MARCKS and ENaC in cultured renal epithelial cells and in the mouse kidney...
May 3, 2017: American Journal of Physiology. Cell Physiology
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