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sodium chloride cotransporter

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https://www.readbyqxmd.com/read/28818393/the-modulation-of-the-phosphorylation-status-of-nkcc1-in-organ-cultured-bovine-lenses-implications-for-the-regulation-of-fiber-cell-and-overall-lens-volume
#1
Irene Vorontsova, Paul J Donaldson, Zhiying Kong, Chiharu Wickremesinghe, Leo Lam, Julie C Lim
In this study we have used an antibody that specifically detects the phosphorylation status of the Sodium/Potassium/2 Chloride Cotransporter (NKCC1) to study whether the activity of NKCC1 can be regulated in organ cultured bovine lenses. Western blotting was first used to confirm the expression of NKCC1, phosphorylated NKCC1 (NKCC1-P) and the regulatory kinases WNK/SPAK and phosphatases PP1/PP2A in bovine lenses at the protein level. Changes to NKCC1-P status were then assessed by organ culturing bovine lenses in either isotonic, hypertonic or hypotonic solutions in the presence or absence of the NKCC inhibitor, bumetanide, or phosphatase inhibitors okadaic acid and calyculin A...
August 14, 2017: Experimental Eye Research
https://www.readbyqxmd.com/read/28762276/synthesis-of-aryl-c-glycosides-via-iron-catalyzed-cross-coupling-of-halosugars-stereoselective-anomeric-arylation-of-glycosyl-radicals
#2
Laksmikanta Adak, Shintaro Kawamura, Gabriel Toma, Toshio Takenaka, Katsuhiro Isozaki, Hikaru Takaya, Akihiro Orita, Ho C Li, Tony K M Shing, Masaharu Nakamura
We have developed a novel diastereoselective iron-catalyzed cross-coupling reaction of various glycosyl halides with aryl metal reagents for the efficient synthesis of aryl C-glycosides, which are of significant pharmaceutical interest due to their biological activities and resistance toward metabolic degradation. A variety of aryl, heteroaryl, and vinyl metal reagents can be cross-coupled with glycosyl halides in high yields in the presence of a well-defined iron complex, composed of iron(II) chloride and a bulky bisphosphine ligand, TMS-SciOPP...
August 1, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28759755/the-roles-of-sodium-glucose-cotransporter-2-inhibitors-in-preventing-kidney-injury-in-diabetes
#3
REVIEW
Krit Jaikumkao, Anchalee Pongchaidecha, Varanuj Chatsudthipong, Siriporn C Chattipakorn, Nipon Chattipakorn, Anusorn Lungkaphin
Diabetic nephropathy (DN) is the leading cause of end stage renal disease (ESRD) worldwide. The early effective treatment of high plasma glucose could delay or prevent the onset of DN. Sodium-glucose cotransporter 2 (SGLT2) inhibitors are new target treatments for ameliorating high plasma glucose and help to maintain glucose homeostasis in diabetic patients. Reduced renal glucose reabsorption by SGLT2 inhibition seems to have high potential to improve glycemic control in diabetes mellitus (DM) not only through glucose lowering but also through glucose-independent effects such as blood pressure-lowering and direct renal effects in diabetes...
July 28, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28750403/ablation-of-the-cl-hco3-exchanger-pendrin-enhances-hydrochlorothiazide-induced-diuresis
#4
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...
July 27, 2017: Kidney & Blood Pressure Research
https://www.readbyqxmd.com/read/28744758/gitelman-syndrome-an-analysis-of-the-underlying-pathophysiologic-mechanisms-of-acid-base-and-electrolyte-abnormalities
#5
REVIEW
T D Filippatos, C V Rizos, E Tzavella, M S Elisaf
Gitelman syndrome is the most common inherited tubular disease resulting from mutations of the SLC12A3 gene that encodes the thiazide-sensitive sodium-chloride cotransporter in the early distal convoluted tubules. The review presents the underlying pathophysiologic mechanisms of acid-base and electrolyte abnormalities observed in patients with Gitelman syndrome. The syndrome is usually characterized by hypokalemic metabolic alkalosis in combination with hypomagnesemia and hypocalciuria. Additionally, increased chloride excretion and renin/aldosterone levels, hypophosphatemia (occasionally), hyponatremia (rarely) and glucose intolerance/insulin resistance have been reported...
July 25, 2017: International Urology and Nephrology
https://www.readbyqxmd.com/read/28646163/aldosterone-modulates-the-association-between-ncc-and-enac
#6
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/28598867/pathophysiology-of-antenatal-bartter-s-syndrome
#7
Martin Kömhoff, Kamel Laghmani
PURPOSE OF REVIEW: Antenatal Bartter syndrome (aBS) is a heterogenous disease resulting from defective ion transport in the thick ascending limb of the loop of Henle. Novel insights into the pathophysiology, as well as the recent identification of a novel genetic cause of aBS, merit an update on this topic. RECENT FINDINGS: In aBS, severe salt losing is further aggravated by defective salt sensing in the macula densa, where a reduced tubular salt concentration is perceived and glomerular filtration is increased instead of decreased...
September 2017: Current Opinion in Nephrology and Hypertension
https://www.readbyqxmd.com/read/28557059/effects-of-taurine-on-plasma-glucose-concentration-and-active-glucose-transport-in-the-small-intestine
#8
Yo Tsuchiya, Koichi Kawamata
Taurine lowers blood glucose levels and improves hyperglycemia. However, its effects on glucose transport in the small intestine have not been investigated. Here, we elucidated the effect of taurine on glucose absorption in the small intestine. In the oral glucose tolerance test, addition of 10 mmol/L taurine suppressed the increase in hepatic portal glucose concentrations. To investigate whether the suppressive effect of taurine occurs via down-regulation of active glucose transport in the small intestine, we performed an assay using the everted sac of the rat jejunum...
May 30, 2017: Animal Science Journal, Nihon Chikusan Gakkaihō
https://www.readbyqxmd.com/read/28522431/wnk1-and-p38-mapk-distribution-in-ionocytes-and-accessory-cells-of-euryhaline-teleost-fish-implies-ionoregulatory-function
#9
W S Marshall, R R F Cozzi, M Spieker
Ionocytes of euryhaline teleost fish secrete NaCl, under regulation by serine and threonine kinases, including with-no-lysine kinase (WNK1) and p38 mitogen-activated protein kinase (MAPK). Mummichogs (Fundulus heteroclitus L.) were acclimated to freshwater (FW), full strength seawater (SW) and hypersaline conditions (2SW). Immunocytochemistry of ionocytes in opercular epithelia of fish acclimated to SW and 2SW revealed that WNK1-anti-pT58 phosphoantibody localized strongly to accessory cells and was present in the cytosol of ionocytes, close to cystic fibrosis transmembrane conductance regulator (CFTR) in the apical membrane and the sodium potassium 2 chloride cotransporter (NKCC) in the basolateral membrane...
July 15, 2017: Biology Open
https://www.readbyqxmd.com/read/28511177/familial-hyperkalemia-and-hypertension-fhht-and-klhl3-description-of-a-family-with-a-new-recessive-mutation-s553l-compared-to-a-family-with-a-dominant-mutation-q309r-with-analysis-of-urinary-sodium-chloride-cotransporter
#10
Orit Kliuk-Ben Bassat, Vered Carmon, Aaron Hanukoglu, Liat Ganon, Eias Massalha, Eliezer J Holtzman, Zvi Farfel, Haim Mayan
BACKGROUND: Familial hyperkalemia and hypertension (FHHt) is an inherited disorder manifested by hyperkalemia and hypertension. The following four causative genes were identified: WNK1, WNK4, CUL3, and KLHL3. For the first 3 genes, inheritance is autosomal dominant. For KLHL3, inheritance is mostly dominant. A few cases with autosomal recessive disease were described. The mechanism of these 2 modes of inheritance is not clear. In the recessive form, the phenotype of heterozygotes is not well described...
May 17, 2017: Nephron
https://www.readbyqxmd.com/read/28507171/first-in-man-demonstration-of-direct-endothelin-mediated-natriuresis-and-diuresis
#11
Robert W Hunter, Rebecca Moorhouse, Tariq E Farrah, Iain M MacIntyre, Takae Asai, Peter J Gallacher, Debbie Kerr, Vanessa Melville, Alicja Czopek, Emma E Morrison, Jess R Ivy, James W Dear, Matthew A Bailey, Jane Goddard, David J Webb, Neeraj Dhaun
Endothelin (ET) receptor antagonists are potentially novel therapeutic agents in chronic kidney disease and resistant hypertension, but their use is complicated by sodium and water retention. In animal studies, this side effect arises from ETB receptor blockade in the renal tubule. Previous attempts to determine whether this mechanism operates in humans have been confounded by the hemodynamic consequences of ET receptor stimulation/blockade. We aimed to determine the effects of ET signaling on salt transport in the human nephron by administering subpressor doses of the ET-1 precursor, big ET-1...
May 15, 2017: Hypertension
https://www.readbyqxmd.com/read/28488023/glucose-enhances-rotavirus-enterotoxin-induced-intestinal-chloride-secretion
#12
Liangjie Yin, Rejeesh Menon, Reshu Gupta, Lauren Vaught, Paul Okunieff, Sadasivan Vidyasagar
Rotavirus causes severe diarrhea in small children and is typically treated using glucose-containing oral rehydration solutions; however, glucose may have a detrimental impact on these patients, because it increases chloride secretion and presumably water loss. The rotavirus enterotoxin nonstructural protein 4 (NSP4) directly inhibits glucose-mediated sodium absorption. We examined the effects of NSP4 and glucose on sodium and chloride transport in mouse small intestines and Caco-2 cells. Mouse small intestines and Caco-2 cells were incubated with NSP4114-135 in the presence/absence of glucose...
May 10, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28442491/constitutively-active-spak-causes-hyperkalemia-by-activating-ncc-and-remodeling-distal-tubules
#13
P Richard Grimm, Richard Coleman, Eric Delpire, Paul A Welling
Aberrant activation of with no lysine (WNK) kinases causes familial hyperkalemic hypertension (FHHt). Thiazide diuretics treat the disease, fostering the view that hyperactivation of the thiazide-sensitive sodium-chloride cotransporter (NCC) in the distal convoluted tubule (DCT) is solely responsible. However, aberrant signaling in the aldosterone-sensitive distal nephron (ASDN) and inhibition of the potassium-excretory renal outer medullary potassium (ROMK) channel have also been implicated. To test these ideas, we introduced kinase-activating mutations after Lox-P sites in the mouse Stk39 gene, which encodes the terminal kinase in the WNK signaling pathway, Ste20-related proline-alanine-rich kinase (SPAK)...
April 25, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28385297/renal-tubular-nhe3-is-required-in-the-maintenance-of-water-and-sodium-chloride-homeostasis
#14
Robert A Fenton, Søren B Poulsen, Samantha de la Mora Chavez, Manoocher Soleimani, Jessica A Dominguez Rieg, Timo Rieg
The sodium/proton exchanger isoform 3 (NHE3) is expressed in the intestine and the kidney, where it facilitates sodium (re)absorption and proton secretion. The importance of NHE3 in the kidney for sodium chloride homeostasis, relative to the intestine, is unknown. Constitutive tubule-specific NHE3 knockout mice (NHE3(loxloxCre)) did not show significant differences compared to control mice in body weight, blood pH or bicarbonate and plasma sodium, potassium, or aldosterone levels. Fluid intake, urinary flow rate, urinary sodium/creatinine, and pH were significantly elevated in NHE3(loxloxCre) mice, while urine osmolality and GFR were significantly lower...
August 2017: Kidney International
https://www.readbyqxmd.com/read/28341239/calcineurin-inhibitors-block-sodium-chloride-cotransporter-dephosphorylation-in-response-to%C3%A2-high-potassium-intake
#15
Wakana Shoda, Naohiro Nomura, Fumiaki Ando, Yutaro Mori, Takayasu Mori, Eisei Sohara, Tatemitsu Rai, Shinichi Uchida
Dietary potassium intake is inversely related to blood pressure and mortality. Moreover, the sodium-chloride cotransporter (NCC) plays an important role in blood pressure regulation and urinary potassium excretion in response to potassium intake. Previously, it was shown that NCC is activated by the WNK4-SPAK cascade and dephosphorylated by protein phosphatase. However, the mechanism of NCC regulation with acute potassium intake is still unclear. To identify the molecular mechanism of NCC regulation in response to potassium intake, we used adult C57BL/6 mice fed a 1...
February 2017: Kidney International
https://www.readbyqxmd.com/read/28259499/chlorthalidone-versus-amlodipine-for-hypertension-in-kidney%C3%A2-transplant-recipients-treated-with-tacrolimus-a%C3%A2-randomized-crossover-trial
#16
RANDOMIZED CONTROLLED TRIAL
Arthur D Moes, Dennis A Hesselink, Anton H van den Meiracker, Robert Zietse, Ewout J Hoorn
BACKGROUND: Chlorthalidone is a very effective antihypertensive drug, but it has not been studied prospectively in kidney transplant recipients with hypertension. Recent data indicate that calcineurin inhibitors activate the thiazide-sensitive sodium chloride cotransporter, providing further rationale to test thiazides in this population. STUDY DESIGN: Randomized noninferiority crossover trial (noninferiority margin, -2.8mmHg). SETTING & PARTICIPANTS: Hypertensive kidney transplant recipients using tacrolimus (median duration, 2...
June 2017: American Journal of Kidney Diseases: the Official Journal of the National Kidney Foundation
https://www.readbyqxmd.com/read/28253301/targeting-gene-expression-to-specific-cells-of-kidney-tubules-in-vivo-using-adenoviral-promoter-fragments
#17
Sumiyo Watanabe, Toru Ogasawara, Yoshifuru Tamura, Taku Saito, Toshiyuki Ikeda, Nobuchika Suzuki, Tatsuo Shimosawa, Shigeru Shibata, Ung-Il Chung, Masaomi Nangaku, Shunya Uchida
Although techniques for cell-specific gene expression via viral transfer have advanced, many challenges (e.g., viral vector design, transduction of genes into specific target cells) still remain. We investigated a novel, simple methodology for using adenovirus transfer to target specific cells of the kidney tubules for the expression of exogenous proteins. We selected genes encoding sodium-dependent phosphate transporter type 2a (NPT2a) in the proximal tubule, sodium-potassium-2-chloride cotransporter (NKCC2) in the thick ascending limb of Henle (TALH), and aquaporin 2 (AQP2) in the collecting duct...
2017: PloS One
https://www.readbyqxmd.com/read/28125972/gitelman-syndrome-in-a-south-african-family-presenting-with-hypokalaemia-and-unusual-food-cravings
#18
Pieter Du Toit van der Merwe, Megan A Rensburg, William L Haylett, Soraya Bardien, M Razeen Davids
BACKGROUND: Gitelman syndrome (GS) is an autosomal recessive renal tubular disorder characterised by renal salt wasting with hypokalaemia, metabolic alkalosis, hypomagnesaemia and hypocalciuria. It is caused by mutations in SLC12A3 encoding the sodium-chloride cotransporter on the apical membrane of the distal convoluted tubule. We report a South African family with five affected individuals presenting with hypokalaemia and unusual food cravings. METHODS: The affected individuals and two unaffected first degree relatives were enrolled into the study...
January 26, 2017: BMC Nephrology
https://www.readbyqxmd.com/read/28101242/screening-and-analysis-of-breast-cancer-genes-regulated-by-the-human-mammary-microenvironment-in-a-humanized-mouse-model
#19
Mingjie Zheng, Jue Wang, Lijun Ling, Dandan Xue, Shui Wang, Yi Zhao
Tumor microenvironments play critical regulatory roles in tumor growth. Although mouse cancer models have contributed to the understanding of human tumor biology, the effectiveness of mouse cancer models is limited by the inability of the models to accurately present humanized tumor microenvironments. Previously, a humanized breast cancer model in severe combined immunodeficiency mice was established, in which human breast cancer tissue was implanted subcutaneously, followed by injection of human breast cancer cells...
December 2016: Oncology Letters
https://www.readbyqxmd.com/read/28094030/glucocorticoid-induced-leucine-zipper-protein-regulates-sodium-and-potassium-balance-in-the-distal-nephron
#20
Priyanka Rashmi, GianLuca Colussi, Michael Ng, Xinhao Wu, Atif Kidwai, David Pearce
Glucocorticoid induced leucine zipper protein (GILZ) is an aldosterone-regulated protein that controls sodium transport in cultured kidney epithelial cells. Mice lacking GILZ have been reported previously to have electrolyte abnormalities. However, the mechanistic basis has not been explored. Here we provide evidence supporting a role for GILZ in modulating the balance of renal sodium and potassium excretion by regulating the sodium-chloride cotransporter (NCC) activity in the distal nephron. Gilz(-/-) mice have a higher plasma potassium concentration and lower fractional excretion of potassium than wild type mice...
January 13, 2017: Kidney International
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