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https://www.readbyqxmd.com/read/29416622/mntbap-therapy-attenuates-the-downregulation-of-sodium-transporters-in-obstructive-kidney-disease
#1
Mi Liu, Yangyang Zhu, Ying Sun, Zhaoying Wen, Songming Huang, Guixia Ding, Aihua Zhang, Zhanjun Jia, Yue Zhang
Ureteral obstruction is associated with reduced expressions of renal sodium transporters, which contributes to impaired urinary concentrating capacity. In this study, we employed a synthetic mitochondrial superoxide dismutase 2 (SOD2) mimic MnTBAP to investigate the role of mitochondrial oxidative stress in modulating the sodium transporters in obstructive kidney disease. Following unilateral ureteral obstruction (UUO) for 7 days, a global reduction of sodium transporters including NHE3, NCC, NKCC2, and ENaCα was observed as determined by qRT-PCR, Western Blotting or immunohistochemistry...
January 2, 2018: Oncotarget
https://www.readbyqxmd.com/read/29371419/plasma-potassium-determines-ncc-abundance-in-adult-kidney-specific-%C3%AE-enac-knockout
#2
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 αENaC 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 αENaC 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...
January 25, 2018: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/29357444/renal-potassium-handling-in-rats-with-subtotal-nephrectomy-modeling-and-analysis
#3
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
https://www.readbyqxmd.com/read/29357420/renal-na-handling-defect-associated-with-per1-dependent-non-dipping-hypertension-in-male-mice
#4
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
https://www.readbyqxmd.com/read/29357414/effects-of-a-high-sodium-low-potassium-diet-on-renal-calcium-magnesium-and-phosphate-handling
#5
Jenny van der Wijst, Omar A Z Tutakhel, Caro Bos, A H Jan Danser, Ewout J Hoorn, Joost G J Hoenderop, René J M Bindels
The distal convoluted tubule (DCT) of the kidney plays an important role in blood pressure regulation by modulating Na+ reabsorption via the Na+-Cl- cotransporter (NCC). A diet containing high salt (NaCl) and low K+ activates NCC, thereby causing Na+ retention and a rise in blood pressure. Since high blood pressure, hypertension, is associated with changes in serum calcium (Ca2+) and magnesium (Mg2+) levels, we hypothesized that dietary Na+ and K+ intake affects Ca2+ and Mg2+ transport in the DCT. Therefore, the present study aimed to investigate the effect of a high Na+/low K+ diet on renal Ca2+ and Mg2+ handling...
January 10, 2018: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29350579/evaluation-of-respiratory-motion-corrected-cone-beam-ct-at-end-expiration-in-abdominal-radiotherapy-sites-a-prospective-study
#6
Russell E Kincaid, Agung E Hertanto, Yu-Chi Hu, Abraham J Wu, Karyn A Goodman, Hai D Pham, Ellen D Yorke, Qinghui Zhang, Qing Chen, Gig S Mageras
BACKGROUND: Cone beam computed tomography (CBCT) for radiotherapy image guidance suffers from respiratory motion artifacts. This limits soft tissue visualization and localization accuracy, particularly in abdominal sites. We report on a prospective study of respiratory motion-corrected (RMC)-CBCT to evaluate its efficacy in localizing abdominal organs and improving soft tissue visibility at end expiration. MATERIAL AND METHODS: In an IRB approved study, 11 patients with gastroesophageal junction (GEJ) cancer and five with pancreatic cancer underwent a respiration-correlated CT (4DCT), a respiration-gated CBCT (G-CBCT) near end expiration and a one-minute free-breathing CBCT scan on a single treatment day...
January 19, 2018: Acta Oncologica
https://www.readbyqxmd.com/read/29326302/role-of-clc-k-and-barttin-in-low-potassium-induced-sodium-chloride-cotransporter-activation-and-hypertension-in-mouse-kidney
#7
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
https://www.readbyqxmd.com/read/29323234/caveolin-1-promotes-renal-water-and-salt-reabsorption
#8
Yan Willière, Aljona Borschewski, Andreas Patzak, Tatiana Nikitina, Carsten Dittmayer, Anna L Daigeler, Markus Schuelke, Sebastian Bachmann, Kerim Mutig
Caveolin-1 (Cav1) is essential for the formation of caveolae. Little is known about their functional role in the kidney. We tested the hypothesis that caveolae modulate renal salt and water reabsorption. Wild-type (WT) and Cav1-deficient (Cav1-/-) mice were studied. Cav1 expression and caveolae formation were present in vascular cells, late distal convoluted tubule and principal connecting tubule and collecting duct cells of WT but not Cav1-/- kidneys. Urinary sodium excretion was increased by 94% and urine flow by 126% in Cav1-/- mice (p < 0...
January 11, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29310825/potassium-intake-modulates-the-thiazide-sensitive-sodium-chloride-cotransporter-ncc-activity-via-the-kir4-1-potassium-channel
#9
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
https://www.readbyqxmd.com/read/29131070/pathophysiology-of-post-transplant-hypertension-in-kidney-transplant-focus-on-calcineurin-inhibitors-induced-oxidative-stress-and-renal-sodium-retention-and-implications-with-rhoa-rho-kinase-pathway
#10
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
https://www.readbyqxmd.com/read/28940314/dietary-sodium-induces-a-redistribution-of-the-tubular-metabolic-workload
#11
Khalil Udwan, Ahmed Abed, Isabelle Roth, Eva Dizin, Marc Maillard, Carla Bettoni, Johannes Loffing, Carsten A Wagner, Aurélie Edwards, Eric Feraille
KEY POINTS: Body Na(+) content is tightly controlled by regulated urinary Na(+) excretion. The intrarenal mechanisms mediating adaptation to variations in dietary Na(+) intake are incompletely characterized. We confirmed and expanded observations in mice that variations in dietary Na(+) intake do not alter the glomerular filtration rate but alter the total and cell-surface expression of major Na(+) transporters all along the kidney tubule. Low dietary Na(+) intake increased Na(+) reabsorption in the proximal tubule and decreased it in more distal kidney tubule segments...
November 15, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28877879/uninephrectomy-and-apical-fluid-shear-stress-decrease-enac-abundance-in-collecting-duct-principal-cells
#12
Thomas Ernandez, Khalil Udwan, Alexandra Chassot, Pierre-Yves Martin, Eric Feraille
Acute nephron reduction such as after living kidney donation may increase the risk of hypertension. Uninephrectomy induces major hemodynamic changes in the remaining kidney resulting in rapid increase of single nephron GFR and fluid delivery in the distal nephron. Decreased sodium (Na) fractional reabsorption after the distal tubule has been reported after uninephrectomy in animals preserving volume homeostasis. In the present study, we thought to specifically explore the effect of unilateral nephrectomy on ENaC subunits expression in mice...
September 6, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28750403/ablation-of-the-cl-hco3-exchanger-pendrin-enhances-hydrochlorothiazide-induced-diuresis
#13
Saeed Alshahrani, Manoocher Soleimani
BACKGROUND/AIMS: The Cl-/HCO3- exchanger pendrin and the thiazide-sensitive Na-Cl cotransporter NCC are expressed in the kidney distal nephron and mediate salt absorption. We hypothesized that deletion of pendrin leaves NCC as the major salt absorbing transporter in the distal nephron and therefore enhances salt excretion by hydrochlorothiazide (HCTZ). METHODS: Metabolic cage studies were performed in wild type, pendrin KO and NCC KO mice at baseline and following HCTZ treatment...
2017: Kidney & Blood Pressure Research
https://www.readbyqxmd.com/read/28743496/wnk4-is-indispensable-for-the-pathogenesis-of-pseudohypoaldosteronism-type-ii-caused-by-mutant-klhl3
#14
Koichiro Susa, Eisei Sohara, Daiei Takahashi, Tomokazu Okado, Tatemitsu Rai, Shinichi Uchida
WNK-OSR1/SPAK-NCC signaling cascade is important for regulating salt balance and blood pressure. Activation of WNK-OSR1/SPAK-NaCl cotransporter (NCC) cascade increases sodium reabsorption in the kidney, leading to pseudohypoaldosteronism type II (PHA II) characterized by salt-sensitive hypertension and hyperkalemia. It has been previously demonstrated that the amount of phosphorylated and total NCC markedly decreased in WNK4(-/-) mice, indicating that WNK4 plays a major role for activation of OSR1/SPAK-NCC signaling...
September 23, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28719636/the-non-diuretic-hypotensive-effects-of-thiazides-are-enhanced-during-volume-depletion-states
#15
Saeed Alshahrani, Robert M Rapoport, Kamyar Zahedi, Min Jiang, Michelle Nieman, Sharon Barone, Andrea L Meredith, John N Lorenz, Jack Rubinstein, Manoocher Soleimani
Thiazide derivatives including Hydrochlorothiazide (HCTZ) represent the most common treatment of mild to moderate hypertension. Thiazides initially enhance diuresis via inhibition of the kidney Na+-Cl- Cotransporter (NCC). However, chronic volume depletion and diuresis are minimal while lowered blood pressure (BP) is maintained on thiazides. Thus, a vasodilator action of thiazides is proposed, likely via Ca2+-activated K+ (BK) channels in vascular smooth muscles. This study ascertains the role of volume depletion induced by salt restriction or salt wasting in NCC KO mice on the non-diuretic hypotensive action of HCTZ...
2017: PloS One
https://www.readbyqxmd.com/read/28656378/comparative-transcriptomic-analysis-identifies-evolutionarily-conserved-gene-products-in-the-vertebrate-renal-distal-convoluted-tubule
#16
REVIEW
Yuya Sugano, Chiara Cianciolo Cosentino, Dominique Loffing-Cueni, Stephan C F Neuhauss, Johannes Loffing
Understanding the molecular basis of the complex regulatory networks controlling renal ion transports is of major physiological and clinical importance. In this study, we aimed to identify evolutionarily conserved critical players in the function of the renal distal convoluted tubule (DCT) by a comparative transcriptomic approach. We generated a transgenic zebrafish line with expression of the red fluorescent mCherry protein under the control of the zebrafish DCT-specific promoter of the thiazide-sensitive NaCl cotransporter (NCC)...
August 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28600880/klotho-lacks-an-fgf23-independent-role-in-mineral-homeostasis
#17
Olena Andrukhova, Jessica Bayer, Christiane Schüler, Ute Zeitz, Sathish K Murali, Sibel Ada, Jose M Alvarez-Pez, Alina Smorodchenko, Reinhold G Erben
Fibroblast growth factor-23 (FGF23) is a bone-derived hormone regulating vitamin D hormone production and renal handling of minerals by signaling through an FGF receptor/αKlotho (Klotho) receptor complex. Whether Klotho has FGF23-independent effects on mineral homeostasis is a controversial issue. Here, we aimed to shed more light on this controversy by comparing male and female triple knockout mice with simultaneous deficiency in Fgf23 and Klotho and a nonfunctioning vitamin D receptor (VDR) (Fgf23/Klotho/VDR) with double (Fgf23/VDR, Klotho/VDR, and Fgf23/Klotho) and single Fgf23, Klotho, and VDR mutants...
October 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/28515174/functional-assessment-of-sodium-chloride-cotransporter-ncc-mutants-in-polarized-mammalian-epithelial-cells
#18
COMPARATIVE STUDY
Lena L Rosenbaek, Federica Rizzo, Nanna MacAulay, Olivier Staub, Robert A Fenton
The thiazide-sensitive sodium chloride cotransporter NCC is important for maintaining serum sodium (Na(+)) and, indirectly, serum potassium (K(+)) levels. Functional studies on NCC have used cell lines with native NCC expression, transiently transfected nonpolarized cell lines, or Xenopus laevis oocytes. Here, we developed the use of polarized Madin-Darby canine kidney type I (MDCKI) mammalian epithelial cell lines with tetracycline-inducible human NCC expression to study NCC activity and membrane abundance in the same system...
August 1, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28446151/novel-mutation-in-the-slc12a3-gene-in-a-sri-lankan-family-with-gitelman-syndrome-coexistent-diabetes-a-case-report
#19
Chandrika Jayakanthi Subasinghe, Nirmala Dushyanthi Sirisena, Chula Herath, Knut Erik Berge, Trond Paul Leren, Uditha Bulugahapitiya, Vajira Harshadeva Weerabaddana Dissanayake
BACKGROUND: Gitelman syndrome (GS) is a rare autosomal recessively inherited salt-wasting tubulopathy associated with mutations in the SLC12A3 gene, which encodes for NaCl cotransporter (NCC) in the kidney. CASE PRESENTATION: In this report, we describe two siblings from a Sri Lankan non-consanguineous family presenting with hypokalaemia associated with renal potassium wasting, hypomagnesemia, hypocalciuria and hypereninemic hyperaldosteronism with normal blood pressure...
April 26, 2017: BMC Nephrology
https://www.readbyqxmd.com/read/28430812/nacl-cotransporter-abundance-in-urinary-vesicles-is-increased-by-calcineurin-inhibitors-and-predicts-thiazide-sensitivity
#20
Omar A Z Tutakhel, Arthur D Moes, Marco A Valdez-Flores, Marleen L A Kortenoeven, Mathijs V D Vrie, Sabina Jeleń, Robert A Fenton, Robert Zietse, Joost G J Hoenderop, Ewout J Hoorn, Luuk Hilbrands, René J M Bindels
Animal studies have shown that the calcineurin inhibitors (CNIs) cyclosporine and tacrolimus can activate the thiazide-sensitive NaCl cotransporter (NCC). A common side effect of CNIs is hypertension. Renal salt transporters such as NCC are excreted in urinary extracellular vesicles (uEVs) after internalization into multivesicular bodies. Human studies indicate that CNIs also increase NCC abundance in uEVs, but results are conflicting and no relationship with NCC function has been shown. Therefore, we investigated the effects of CsA and Tac on the abundance of both total NCC (tNCC) and phosphorylated NCC at Thr60 phosphorylation site (pNCC) in uEVs, and assessed whether NCC abundance in uEVs predicts the blood pressure response to thiazide diuretics...
2017: PloS One
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