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sodium chloride cotransporter

Hiroko Hashimoto, Naohiro Nomura, Wakana Shoda, Kiyoshi Isobe, Hiroaki Kikuchi, Kouhei Yamamoto, Takuya Fujimaru, Fumiaki Ando, Takayasu Mori, Tomokazu Okado, Tatemitsu Rai, Shinichi Uchida, Eisei Sohara
OBJECTIVE: Metformin is an antidiabetic drug that is widely used to treat patients with diabetes mellitus. Recent studies have reported that treatment with metformin not only improved blood glucose levels but also reduced blood pressure. However, it remains unclear how metformin reduces blood pressure. We hypothesized that metformin affects sodium reabsorption in the kidneys. METHODS: Urinary sodium excretion and expression of renal sodium transporters were examined in 8-week-old male C57BL/6 mice with acute and chronic treatment of metformin...
March 3, 2018: Metabolism: Clinical and Experimental
Marc-Henri Asmar, Louis Gaboury, Issam Saliba
Objectives Endolymphatic sac (ELS) pathophysiology in Ménière's disease (MD) remains poorly understood. We identified from the literature a group of proteins expressed on the ELS and involved in endolymph volume regulation: aquaporin-2 (AQP2), vasopressin receptor V2R, sodium potassium chloride cotransporter 2 (NKCC2), and transient receptor potential cation channel V4 (TRPV4). Our objective was to determine whether their ELS expression was altered in MD, to better understand the pathophysiology of endolymphatic hydrops...
February 1, 2018: Otolaryngology—Head and Neck Surgery
Andrew Scott Terker, Maria Castaneda-Bueno, Mohammed Zubaerul Ferdaus, Ryan J Cornelius, Kayla J Erspamer, Xiao-Tong Su, Lauren N Miller, James A McCormick, Wen-Hui Wang, Gerardo Gamba, Chao-Ling Yang, David H Ellison
With no lysine kinase 4 (WNK4) is essential to activate the thiazide-sensitive NaCl cotransporter (NCC) along the distal convoluted tubule, an effect central to the phenotype of familial hyperkalemic hypertension. Although effects on potassium and sodium channels along the connecting and collecting tubules have also been documented, WNK4 is typically believed to have little role in modulating sodium chloride reabsorption along the thick ascending limb of the loop of Henle. Yet wnk4-/- mice (knockout mice lacking WNK4) do not demonstrate the hypocalciuria typical of pure distal convoluted tubule dysfunction...
February 7, 2018: American Journal of Physiology. Renal Physiology
M Giovanola, A Vollero, R Cinquetti, E Bossi, L R Forrest, E Di Cairano, M Castagna
The crystallizations of the prokaryotic LeuT and of the eukaryotic DAT and SERT transporters represent important steps forward in the comprehension of the molecular physiology of Neurotransmitter:Sodium Symporters, although the molecular determinants of the coupling mechanism and of ion selectivity still remain to be fully elucidated. The insect NSS homologue KAAT1 exhibits unusual physiological features, such as the ability to use K+ as the driver ion, weak chloride dependence, and the ability of the driver ion to influence the substrate selectivity; these characteristics can help to define the molecular determinants of NSS function...
January 30, 2018: Biochimica et Biophysica Acta
Emilie Boscardin, Romain Perrier, Chloé Sergi, Marc P Maillard, Johannes Loffing, Dominique Loffing-Cueni, Robert Koesters, Bernard C Rossier, Edith Hummler
The amiloride-sensitive epithelial sodium channel (ENaC) and the thiazide-sensitive sodium chloride cotransporter (NCC) are key regulators of sodium and potassium and colocalize in the late distal convoluted tubule of the kidney. Loss of the α ENaC subunit leads to a perinatal lethal phenotype characterized by sodium loss and hyperkalemia resembling the human syndrome pseudohypoaldosteronism type 1 (PHA-I). In adulthood, inducible nephron-specific deletion of α ENaC in mice mimics the lethal phenotype observed in neonates, and as in humans, this phenotype is prevented by a high sodium (HNa+ )/low potassium (LK+ ) rescue diet...
March 2018: Journal of the American Society of Nephrology: JASN
Anita T Layton, Aurélie Edwards, Volker Vallon
We sought to decipher the mechanisms underlying the kidney's response to changes in K+ load and intake, under physiological and pathophysiological conditions. To accomplish that goal, we applied a published computational model of epithelial transport along rat nephrons in a \Red{sham}, uninephrectomized (UNX), and 5/6-nephrectomized (5/6-NX) \Red{rats that also considers adaptations in GFR and tubular growth}. Model simulations \Red{of an acute K+ load} indicate that elevated expression levels and activities of Na+/K+-ATPase, epithelial sodium channels (ENaC), large conductance Ca2+-activated K+ channels (BK), and renal outer medullary K+ channels (ROMK), together with downregulation of sodium-chloride cotransporters (NCC), increase K+ secretion along the connecting tubule, resulting in a > 6-fold increase in urinary K+ excretion in \Red{sham rats}, which substantially exceeds the filtered K+ load...
December 13, 2017: American Journal of Physiology. Renal Physiology
Lauren Grace Douma, Meaghan Rayann Holzworth, Kristen Solocinski, Sarah Howland Masten, Amber Holly Miller, Kit-Yan Cheng, I Jeanette Lynch, Brian D Cain, Charles S Wingo, Michelle L Gumz
Many physiological functions have a circadian rhythm, including blood pressure (BP). BP is highest during the active phase whereas during the rest period BP dips 10%-20%. Patients that do not experience this dip at night are termed "non-dippers." Non-dipping hypertension is associated with increased risk of cardiovascular disease. The mechanisms underlying non-dipping hypertension are not understood. Without the circadian clock gene Per1, C57BL/6J mice develop non-dipping hypertension on a high-salt diet plus mineralocorticoid treatment (HS/DOCP)...
January 10, 2018: American Journal of Physiology. Renal Physiology
Naohiro Nomura, Wakana Shoda, Yuanlong Wang, Shintaro Mandai, Taisuke Furusho, Daiei Takahashi, Moko Zeniya, Eisei Sohara, Tatemitsu Rai, Shinichi Uchida
The sodium-chloride cotransporter (NCC) has been identified as a key molecule regulating potassium balance. The mechanisms of NCC regulation during low extracellular potassium concentrations have been studied in vitro. These studies have shown that hyperpolarization increased chloride efflux, leading to the activation of chloride-sensitive WNK kinases and their downstream molecules, including STE20/SPS1-related proline/alanine-rich kinase (SPAK) and NCC. However, this mechanism was not studied in vivo Previously, we developed the barttin hypomorphic mouse ( Bsndneo/neo mice), expressing very low levels of barttin and ClC-K channels, because barttin is an essential ß-subunit of ClC-K...
January 11, 2018: Bioscience Reports
Ming-Xiao Wang, Catherina A Cuevas, Xiao-Tong Su, Peng Wu, Zhong-Xiuzi Gao, Dao-Hong Lin, James A McCormick, Chao-Ling Yang, Wen-Hui Wang, David H Ellison
Kir4.1 in the distal convoluted tubule plays a key role in sensing plasma potassium and in modulating the thiazide-sensitive sodium-chloride cotransporter (NCC). Here we tested whether dietary potassium intake modulates Kir4.1 and whether this is essential for mediating the effect of potassium diet on NCC. High potassium intake inhibited the basolateral 40 pS potassium channel (a Kir4.1/5.1 heterotetramer) in the distal convoluted tubule, decreased basolateral potassium conductance, and depolarized the distal convoluted tubule membrane in Kcnj10flox/flox mice, herein referred to as control mice...
January 6, 2018: Kidney International
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
Chaobin Qin, Liping Yang, Wenjia Zheng, Xiao Yan, Ronghua Lu, Dizhi Xie, Guoxing Nie
The co-transport of sodium and glucose is the first step for intestinal glucose absorption. Dietary glucose and sodium chloride (NaCl) may facilitate this physiological process in common carp (Cyprinus carpio L.). To test this hypothesis, we first investigated the feeding rhythm of intestinal glucose absorption. Carps were fed to satiety once a day (09:00 a.m.) for 1 month. Intestinal samples were collected at 01:00, 05:00, 09:00, 13:00, 17:00 and 21:00. Result showed that food intake greatly enhanced sodium/glucose cotransporter 1 (SGLT1) and glucose transporter type 2 (GLUT2) expressions, and improved glucose absorption, with highest levels at 09:00 a...
December 13, 2017: Biochemical and Biophysical Research Communications
Yuichi Uwai, Tatsuya Kawasaki, Tomohiro Nabekura
We previously reported the contribution of sodium-phosphate cotransporter to the tubular reabsorption of lithium in rats. In the present study, the dose dependency of the renal handling of lithium was examined in rats. When lithium chloride at 1.25 mg/kg, 2.5 mg/kg and 25 mg/kg was intravenously injected as a bolus, the areas under the plasma concentration-time curve of lithium until 60 minutes were calculated to be 6.23 mEq·min/l, 8.77 mEq·min/l and 64.6 mEq·min/l, respectively. The renal clearance of lithium and its fractional excretion increased with increments in the dose administered...
February 2018: Biopharmaceutics & Drug Disposition
Lorenzo A Calò, Verdiana Ravarotto, Francesca Simioni, Elena Naso, Francesco Marchini, Luciana Bonfante, Lucrezia Furian, Paolo Rigotti
Post-transplant hypertension is a common occurrence during treatment with calcineurin inhibitors (CNIs) in kidney transplant population. The pathogenesis of vasoconstriction induced by CNIs involves vascular tone alterations and kidney sodium transport regulation. Among the factors involved a key role is played by the activation of intrarenal renin-angiotensin system with enhanced release of Angiotensin II (Ang II) and increase of oxidative stress. A common pathway between oxidative stress and hypertension induced by CNIs may be identified in the involvement of the activation of RhoA/Rho kinase pathway, key for the induction of hypertension and cardiovascular-renal remodeling, of the oxidative stress mediated increased nitric oxide (NO) metabolism and increased renal sodium retention via increased activity of thiazide-sensitive sodium chloride cotransporter (NCC) in the distal tubule...
October 16, 2017: Kidney & Blood Pressure Research
Kristin J Bergsland, Fredric L Coe, Joan H Parks, John R Asplin, Elaine M Worcester
Background: Hypophosphatemia (HYP) is common among calcium stone formers (SFs) and in rare cases is associated with mutations in sodium-phosphate cotransporters or in Na+/H+ exchanger regulatory factor 1 (NHERF1), but the majority of cases are unexplained. We hypothesized that reduced sodium-phosphate cotransporter activity mediated via NHERF1 or a similar PDZ domain-containing protein, causes HYP. If so, other transport activities controlled by NHERF1, such as NHE3 and URAT1, might be reduced in HYP...
November 6, 2017: Nephrology, Dialysis, Transplantation
Brandi M Wynne, Cameron G McCarthy, Theodora Szasz, Patrick A Molina, Arlene B Chapman, R Clinton Webb, Janet D Klein, Robert S Hoover
AIM: Protein kinase Cα (PKCα) is a critical regulator of multiple cell signaling pathways including gene transcription, posttranslation modifications and activation/inhibition of many signaling kinases. In regards to the control of blood pressure, PKCα causes increased vascular smooth muscle contractility, while reducing cardiac contractility. In addition, PKCα has been shown to modulate nephron ion transport. However, the role of PKCα in modulating mean arterial pressure (MAP) has not been investigated...
November 8, 2017: Journal of Hypertension
Yaya Zhou, Wei Sun, Ning Chen, Chen Xu, Xinxin Wang, Kun Dong, Binxue Zhang, Jian Zhang, Ning Hao, Aihua Sun, Handong Wei, Fuchu He, Ying Jiang
Metastasis is the essential cause for the high mortality of hepatocellular carcinoma (HCC). In order to investigate the mechanism of metastasis, and to discover therapeutic targets for HCC, the quantitative proteomic technique was applied to characterize the plasma membrane proteins of two HCC cell lines with low (MHCC97L) or high (MHCC97H) metastatic potentials. One of the plasma membrane proteins, sodium-potassium-chloride cotransporter 1 (NKCC1), was upregulated in MHCC97H cell line. Immunohistochemistry result in HCC patients showed that NKCC1 expression was associated with poor differentiation and microvascular invasion...
September 12, 2017: Oncotarget
Lena L Rosenbaek, Federica Rizzo, Qi Wu, Lorena Rojas-Vega, Gerardo Gamba, Nanna MacAulay, Olivier Staub, Robert A Fenton
The renal sodium chloride cotransporter, NCC, in the distal convoluted tubule is important for maintaining body Na(+) and K(+) homeostasis. Endogenous NCC is highly ubiquitylated, but the role of individual ubiquitylation sites is not established. Here, we assessed the role of 10 ubiquitylation sites for NCC function. Transient transfections of HEK293 cells with human wildtype (WT) NCC or various K to R mutants identified greater membrane abundance for K706R, K828R and K909R mutants. Relative to WT-NCC, stable tetracycline inducible MDCKI cell lines expressing K706R, K828R and K909R mutants had significantly higher total and phosphorylated NCC levels at the apical plasma membrane under basal conditions...
October 11, 2017: Scientific Reports
Carolina M Alvadia, Theis Sommer, Kaare Bjerregaard-Andersen, Helle Hasager Damkier, Michele Montrasio, Christian Aalkjaer, J Preben Morth
The sodium-driven chloride/bicarbonate exchanger (NDCBE) is essential for maintaining homeostatic pH in neurons. The crystal structure at 2.8 Å resolution of the regulatory N-terminal domain of human NDCBE represents the first crystal structure of an electroneutral sodium-bicarbonate cotransporter. The crystal structure forms an equivalent dimeric interface as observed for the cytoplasmic domain of Band 3, and thus establishes that the consensus motif VTVLP is the key minimal dimerization motif. The VTVLP motif is highly conserved and likely to be the physiologically relevant interface for all other members of the SLC4 family...
September 21, 2017: Scientific Reports
Peter M Piermarini, Daniel C Akuma, John C Crow, Taylor L Jamil, Willa G Kerkhoff, Kenyatta C M F Viel, Christopher M Gillen
The yellow fever mosquito, Aedes aegypti, has three genes that code for proteins with sequence similarity to vertebrate Na+-K+-Cl- cotransporters (NKCCs) of the solute-linked carrier 12 superfamily of cation-chloride cotransporters (CCCs). We hypothesized that these mosquito NKCC orthologues have diverged to perform distinct roles in salt secretion and absorption. In phylogenetic analyses, one protein (aeNKCC1) groups with a Drosophila melanogaster NKCC that mediates salt secretion whereas two others (aeCCC2 and aeCCC3) group with a Drosophila transporter that is not functionally characterized...
December 2017: Comparative Biochemistry and Physiology. Part A, Molecular & Integrative Physiology
Caroline Pin-Barre, Annabelle Constans, Jeanick Brisswalter, Christophe Pellegrino, Jérôme Laurin
BACKGROUND AND PURPOSE: This study was designed to compare the effects of high-intensity interval training (HIT) and moderate-intensity aerobic training (MOD) on functional recovery and cerebral plasticity during the first 2 weeks after cerebral ischemia. METHODS: Rats were randomized as follows: control (n=15), SHAM (n=9), middle cerebral artery occlusion (n=13), middle cerebral artery occlusion at day 1 (n=7), MOD (n=13), and HIT (n=13). Incremental tests were performed at day 1 (D1) and 14 (D14) to identify the running speed associated with the lactate threshold ( S LT ) and the maximal speed ( S max )...
October 2017: Stroke; a Journal of Cerebral Circulation
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