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https://www.readbyqxmd.com/read/29226589/hydrochlorothiazide-and-acute-urinary-acidification-the-voltage-hypothesis-of-enac-dependent-h-secretion-refuted
#1
Niklas Ayasse, Pauline I A de Bruijn, Peder Berg, Mads V Sørensen, Jens Leipziger
AIM: The 'voltage hypothesis' of H+ secretion states that urinary acidification following increased Na+ delivery to the collecting duct (CD) is ENaC-dependent leading to transepithelial voltage-dependent increase in H+ secretion. We recently showed that furosemide acidifies the urine independently of ENaC activity. If the voltage hypothesis holds, hydrochlorothiazide (HCT) must acidify the urine. We here tested the acute effect of HCT on urine pH under normal and high ENaC expression...
December 11, 2017: Acta Physiologica
https://www.readbyqxmd.com/read/29187368/n-linked-glycans-are-required-on-epithelial-na-channel-subunits-for-maturation-and-surface-expression
#2
Ossama B Kashlan, Carol L Kinlough, Michael M Myerburg, Shujie Shi, Jingxin Chen, Brandon M Blobner, Teresa M Buck, Jeffrey L Brodsky, Rebecca P Hughey, Thomas R Kleyman
Epithelial Na+ channel (ENaC) subunits undergo N-linked glycosylation in the endoplasmic reticulum where they assemble into an αβγ complex. Six, thirteen and five consensus sites (Asn-x-Ser/Thr) for N-glycosylation reside in the extracellular domains of the mouse α, β and γ subunits, respectively. Because the importance of ENaC N-linked glycans has not been fully addressed, we examined the effect of preventing N-glycosylation of specific subunits on channel function, expression, maturation, and folding...
November 29, 2017: American Journal of Physiology. Renal Physiology
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
#3
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
#4
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
#5
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/29178032/lithium-increases-ammonium-excretion-leading-to-altered-urinary-acid-base-buffer-composition
#6
Francesco Trepiccione, Claudia Altobelli, Giovambattista Capasso, Birgitte Mønster Christensen, Sebastian Frische
Previous reports identify a voltage dependent distal renal tubular acidosis (dRTA) secondary to lithium (Li+) salt administration. This was based on the inability of Li+-treated patients to increase the urine-blood (U-B) pCO2 when challenged with NaHCO3 and, the ability of sodium neutral phosphate or Na2SO4 administration to restore U-B pCO2 in experimental animal models. The underlying mechanisms for the Li+-induced dRTA are still unknown. To address this point, a 7 days time course of the urinary acid-base parameters was investigated in rats challenged with LiCl, LiCitrate, NaCl, or NaCitrate...
November 24, 2017: Journal of Nephrology
https://www.readbyqxmd.com/read/29154907/an-integrated-mathematical-epithelial-cell-model-for-airway-surface-liquid-regulation-by-mechanical-forces
#7
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/29144530/liddle-s-syndrome-in-an-african-male-due-to-a-novel-frameshift-mutation-in-the-beta-subunit-of-the-epithelial-sodium-channel-gene
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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/29120692/epithelial-na-channel-regulation-by-extracellular-and-intracellular-factors
#14
Thomas R Kleyman, Ossama B Kashlan, Rebecca P Hughey
Epithelial Na(+) channels (ENaCs) are members of the ENaC/degenerin family of ion channels that evolved to respond to extracellular factors. In addition to being expressed in the distal aspects of the nephron, where ENaCs couple the absorption of filtered Na(+) to K(+) secretion, these channels are found in other epithelia as well as nonepithelial tissues. This review addresses mechanisms by which ENaC activity is regulated by extracellular factors, including proteases, Na(+), and shear stress. It also addresses other factors, including acidic phospholipids and modification of ENaC cytoplasmic cysteine residues by palmitoylation, which enhance channel activity by altering interactions of the channel with the plasma membrane...
November 8, 2017: Annual Review of Physiology
https://www.readbyqxmd.com/read/29108246/mrp4-regulates-enac-dependent-creb-cox-2-pge2-signaling-during-embryo-implantation
#15
Jun-Jiang Chen, Yan Wang, Xiaojing Meng, Ye Chun Ruan, Fei Zou, Hsiao Chang Chan
Multi-drug resistance protein 4 (MRP4), a potential chemotherapeutic target as well as a transporter for endogenous signaling molecules (e.g. prostaglandins), is known to be expressed in the endometrium, although its possible role(s) in the physiology of the endometrium remains unknown. Here, we show that MRP4 is upregulated at implantation window and localized to the basolateral membrane of the endometrial epithelium, the interface between the epithelium and stroma in mice. In human endometrial epithelial cells, MRP4 expression is upregulated by ENaC activation and the inhibition of MRP4 blocks ENaC-dependent PGE2 release as well as phosphorylation of CREB...
October 3, 2017: Oncotarget
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
#16
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
https://www.readbyqxmd.com/read/29102290/ion-channels-as-targets-to-treat-cystic-fibrosis-lung-disease
#17
S Lorraine Martin, Vinciane Saint-Criq, Tzyh-Chang Hwang, László Csanády
Lung health relies on effective mucociliary clearance and innate immune defence mechanisms. In cystic fibrosis (CF), an imbalance in ion transport due to an absence of chloride ion secretion, caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) and a concomitant sodium hyperabsorption, caused by dyregulation of the epithelial sodium channel (ENaC), results in mucus stasis which predisposes the lungs to cycles of chronic infection and inflammation leading to lung function decline...
October 25, 2017: Journal of Cystic Fibrosis: Official Journal of the European Cystic Fibrosis Society
https://www.readbyqxmd.com/read/29074490/lung-disease-phenotypes-caused-by-over-expression-of-combinations-of-alpha-beta-and-gamma-subunits-of-the-epithelial-sodium-channel-in-mouse-airways
#18
Alessandra Livraghi-Butrico, Kristen J Wilkinson, Allison S Volmer, Rodney C Gilmore, Troy D Rogers, Ray A Caldwell, Kimberlie A Burns, Charles R Esther, Marcus A Mall, Richard C Boucher, Wanda K O'Neal, Barbara R Grubb
The epithelial Na+ channel (ENaC) regulates airway surface hydration. In mouse airways, ENaC is composed of three subunits, alpha (α), beta (β), and gamma (γ), which are differentially expressed (α > β > γ). Airway-targeted overexpression of the β subunit results in Na+ hyperabsorption causing airway surface dehydration, hyperconcentrated mucus with delayed clearance, lung inflammation, and perinatal mortality. Notably, mice overexpressing the α or γ subunit do not exhibit airway Na+ hyperabsorption nor lung pathology...
October 26, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/29070571/lithium-induces-aerobic-glycolysis-and-glutaminolysis-in-collecting-duct-principal-cells
#19
Mohammad Alsady, Theun de Groot, Marleen Louise Adriënne Kortenoeven, Claudia Carmone, Kim Neijman, Melissa Bekkenkamp-Grovenstein, Udo Engelke, Ron Wevers, Ruben Baumgarten, Ron Korstanje, Peter M T Deen
Lithium, given to bipolar disorder patients, causes nephrogenic diabetes insipidus (Li-NDI), a urinary concentrating defect. Li-NDI is due to downregulation of principal cell AQP2 expression, which coincides with principal cell proliferation. The metabolic effect of lithium on principal cells, however, is unknown and investigated here. Earlier, we have shown that the carbonic anhydrase (CA) inhibitor acetazolamide attenuated Li-induced downregulation in mouse collecting duct (mpkCCD) cells. Of the eight CAs present in mpkCCD cells, siRNA and drug treatments showed that downregulation of CA9 and to some extent CA12 attenuated Li-induced AQP2 downregulation...
October 25, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29061720/role-of-kidneys-in-sex-differences-in-angiotensin-ii-induced-hypertension
#20
Lei Wang, Ximing Wang, Helena Y Qu, Shan Jiang, Jie Zhang, Liying Fu, Jacentha Buggs, Bo Pang, Jin Wei, Ruisheng Liu
The significance of kidneys in regulation of sodium and water balance and hemodynamics has been demonstrated both in patients and animal models. In the present study, we tested our hypothesis that kidneys play an essential role in control of sex differences in angiotensin II (Ang II)-dependent hypertension. Kidney transplantations (KTXs) were performed between male (M) and female (F) C57BL/6 mice (donor→recipient: F→F, M→M, F→M, and M→F). Radiotelemetry transmitters were implanted for measurement of mean arterial pressure during the infusion of Ang II (600 ng·kg(-1)·min(-1))...
October 23, 2017: Hypertension
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