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Pendrin

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https://www.readbyqxmd.com/read/29777056/the-extracellular-loop-of-pendrin-and-prestin-modulates-their-voltage-sensing-property
#1
Makoto F Kuwabara, Koichiro Wasano, Satoe Takahashi, Justin Bodner, Tomotaka Komori, Sotaro Uemura, Jing Zheng, Tomohiro Shima, Kazuaki Homma
Pendrin and prestin belong to the solute carrier 26 (SLC26) family of anion transporters. Prestin is unique among the SLC26 family members in that it displays voltage-driven motor activity (electromotility) and concurrent gating currents that manifests as nonlinear cell membrane electrical capacitance (NLC). Although the anion transport mechanism of the SLC26 proteins has begun to be elucidated, the molecular mechanism of electromotility, which is thought to be evolved from an ancestral ion transport mechanism, still remains largely elusive...
May 18, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29774167/complete-hypokalemic-quadriparesis-as-a-first-presentation-of-sj%C3%A3-gren-syndrome
#2
Jason An, Branko Braam
Rationale: We hope to increase awareness that hypokalemic paralysis may be the first presentation of Sjögren syndrome, for which potassium-sparing diuretics can be an effective adjunct to potassium replenishment. Presenting concerns: A 73-year-old female presented to a peripheral hospital with quadriparesis and a critically low serum potassium of 1.6 mmol/L with U waves on the electrocardiogram (ECG). The initial arterial blood gas showed a pH of 7.19, bicarbonate of 13 mEq/L, and a CO2 of 35 mm Hg...
2018: Canadian Journal of Kidney Health and Disease
https://www.readbyqxmd.com/read/29773687/the-role-of-intercalated-cell-nedd4-2-in-bp-regulation-ion-transport-and-transporter-expression
#3
Masayoshi Nanami, Truyen D Pham, Young Hee Kim, Baoli Yang, Roy L Sutliff, Olivier Staub, Janet D Klein, Karen I Lopez-Cayuqueo, Regine Chambrey, Annie Y Park, Xiaonan Wang, Vladimir Pech, Jill W Verlander, Susan M Wall
Background Nedd4-2 is an E3 ubiquitin-protein ligase that associates with transport proteins, causing their ubiquitylation, and then internalization and degradation. Previous research has suggested a correlation between Nedd4-2 and BP. In this study, we explored the effect of intercalated cell (IC) Nedd4-2 gene ablation on IC transporter abundance and function and on BP. Methods We generated IC Nedd4-2 knockout mice using Cre-lox technology and produced global pendrin/ Nedd4-2 null mice by breeding global Nedd4-2 null ( Nedd4-2-/- ) mice with global pendrin null ( Slc26a4-/- ) mice...
May 17, 2018: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/29772533/homology-of-pendrin-sodium-iodide-symporter-and-apical-iodide-transporter
#4
Salvatore Benvenga, Fabrizio Guarneri
We observed local homology between human pendrin and sodium/iodide symporter (NIS), that was absent in the NIS-homologous sodium/monocarboxylate transporter or apical iodide transporter (AIT) which, however, does not transport iodide. Thus, we analyzed the full proteins. They shared 63 identical and 66 similar residues (overall homology 14.4%, but 21% when omitting intervening sequences of 15 or more residues). Pendrin was more homologous to NIS (25%) than AIT (20%), particularly in the STAS domain (sulfate transporter and antisigma factor antagonist)...
June 1, 2018: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/29739340/mutation-analysis-of-slc26a4-pendrin-gene-in-a-brazilian-sample-of-hearing-impaired-subjects
#5
Renata Watanabe Nonose, Karina Lezirovitz, Maria Teresa Balester de Mello Auricchio, Ana Carla Batissoco, Guilherme Lopes Yamamoto, Regina Célia Mingroni-Netto
BACKGROUND: Mutations in the SLC26A4 gene are associated with Pendred syndrome and autosomal recessive non-syndromic deafness (DFNB4). Both disorders have similar audiologic characteristics: bilateral hearing loss, often severe or profound, which may be associated with abnormalities of the inner ear, such as dilatation of the vestibular aqueduct or Mondini dysplasia. But, in Pendred syndrome (OMIM #274600), with autosomal recessive inheritance, besides congenital sensorineural deafness, goiter or thyroid dysfunctions are frequently present...
May 8, 2018: BMC Medical Genetics
https://www.readbyqxmd.com/read/29667915/chronic-lithium-treatment-induces-novel-patterns-of-pendrin-localization-and-expression
#6
Nathaniel J Himmel, Yirong Wang, Daniel A Rodriguez, Michael A Sun, Mitsi A Blount
Prolonged lithium treatment is associated with various renal side effects and is known to induce inner medullary collecting duct (IMCD) remodeling. In animals treated with lithium, the fraction of intercalated cells (ICs), which are responsible for acid-base homeostasis, increases as compared to renal principal cells (PCs). In order to investigate the intricacies of lithium-induced IMCD remodeling, male Sprague Dawley rats were fed a lithium-enriched diet for 0,1, 2, 3, 6, 9, or 12 weeks. Urine osmolality was decreased at 1 week, and from 2-12 weeks, animals were severely polyuric...
April 18, 2018: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29580969/unconventional-secretion-of-transmembrane-proteins
#7
REVIEW
Heon Yung Gee, Jiyoon Kim, Min Goo Lee
Over the past 20 years it has become evident that eukaryotic cells utilize both conventional and unconventional pathways to deliver proteins to their target sites. Most proteins with a signal peptide and/or a transmembrane domain are conventionally transported through the endoplasmic reticulum to the Golgi apparatus and then to the plasma membrane. However, an increasing number of both soluble cargos (Type I, II, and III) and integral membrane proteins (Type IV) have been found to reach the plasma membrane via unconventional protein secretion (UPS) pathways that bypass the Golgi apparatus under certain conditions, such as cellular stress or development...
March 23, 2018: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/29536650/most-bicarbonate-secretion-by-calu-3-cells-is-mediated-by-cftr-and-independent-of-pendrin
#8
Junwei Huang, Dusik Kim, Jiajie Shan, Asmahan Abu-Arish, Yishan Luo, John W Hanrahan
Bicarbonate plays an important role in airway host defense, however, its transport mechanisms remain uncertain. Here we examined the relative contributions of the anion channel CFTR (cystic fibrosis transmembrane conductance regulator, ABCC7) and the anion exchanger pendrin (SLC26A4) to HCO3 - secretion by the human airway cell line Calu-3. Pendrin and CFTR were both detected in parental Calu-3 cells, although mRNA and protein expression appeared higher for CFTR than for pendrin. Targeting pendrin transcripts with lentiviral shRNA reduced pendrin detection by immunofluorescence staining but did not alter the rates of HCO3 - or fluid secretion, HCO3 - transport under pH-stat conditions, or net HCO3 - flux across basolaterally permeabilized monolayers...
March 2018: Physiological Reports
https://www.readbyqxmd.com/read/29482189/downregulation-of-the-cl-hco3-exchanger-pendrin-in-kidneys-of-mice-with-cystic-fibrosis-role-in-the-pathogenesis-of-metabolic-alkalosis
#9
Mujan Varasteh Kia, Sharon Barone, Alicia A McDonough, Kamyar Zahedi, Jie Xu, Manoocher Soleimani
BACKGROUND/AIMS: Patients with cystic fibrosis (CF) are prone to the development of metabolic alkalosis; however, the pathogenesis of this life threatening derangement remains unknown. We hypothesized that altered acid base transport machinery in the kidney collecting duct underlies the mechanism of impaired bicarbonate elimination in the CF kidney. METHODS: Balance studies in metabolic cages were performed in WT and CFTR knockout (CF) mice with the intestinal rescue in response to bicarbonate loading or salt restriction, and the expression levels and cellular distribution of acid base and electrolyte transporters in the proximal tubule, collecting duct and small intestine were examined by western blots, northern blots and/or immunofluorescence labeling...
2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29437784/role-of-iodide-metabolism-in-physiology-and-cancer
#10
REVIEW
Antonio De la Vieja, Pilar Santisteban
Iodide (I- ) metabolism is crucial for the synthesis of thyroid hormones (THs) in the thyroid and the subsequent action of these hormones in the organism. I- is principally transported by the sodium iodide symporter (NIS) and by the anion exchanger PENDRIN, and recent studies have demonstrated the direct participation of new transporters including anoctamin 1 (ANO1), cystic fibrosis transmembrane conductance regulator (CFTR) and sodium multivitamin transporter (SMVT). Several of these transporters have been found expressed in various tissues, implicating them in I- recycling...
April 2018: Endocrine-related Cancer
https://www.readbyqxmd.com/read/29412702/%C3%AE-ketoglutarate-stimulates-pendrin-dependent-cl-absorption-in-the-mouse-ccd-through-protein-kinase-c
#11
Yoskaly Lazo-Fernandez, Paul A Welling, Susan M Wall
Alpha-ketoglutarate (αKG) is a citric acid cycle intermediate and a glutamine catabolism product. It is also the natural ligand of OXGR1, a Gq-protein coupled receptor expressed on the apical membrane of intercalated cells. In the CCD, Cl- /HCO3 - exchange increases upon αKG binding to the OXGR1. To determine the signaling pathway(s) by which αKG stimulates Cl- absorption, we examined αKG-stimulated Cl- absorption in isolated perfused mouse CCDs. αKG increased electroneutral Cl- absorption in CCDs from wild type mice, but had no effect on Cl- absorption in pendrin KO mice...
February 7, 2018: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29320412/functional-testing-of-slc26a4-variants-clinical-and-molecular-analysis-of-a-cohort-with-enlarged-vestibular-aqueduct-from-austria
#12
Sebastian Roesch, Emanuele Bernardinelli, Charity Nofziger, Miklós Tóth, Wolfgang Patsch, Gerd Rasp, Markus Paulmichl, Silvia Dossena
The prevalence and spectrum of sequence alterations in the SLC26A4 gene, which codes for the anion exchanger pendrin, are population-specific and account for at least 50% of cases of non-syndromic hearing loss associated with an enlarged vestibular aqueduct. A cohort of nineteen patients from Austria with hearing loss and a radiological alteration of the vestibular aqueduct underwent Sanger sequencing of SLC26A4 and GJB2 , coding for connexin 26. The pathogenicity of sequence alterations detected was assessed by determining ion transport and molecular features of the corresponding SLC26A4 protein variants...
January 10, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29285423/renal-intercalated-cells-and-blood-pressure-regulation
#13
REVIEW
Susan M Wall
Type B and non-A, non-B intercalated cells are found within the connecting tubule and the cortical collecting duct. Of these cell types, type B intercalated cells are known to mediate Cl- absorption and HCO3 - secretion largely through pendrin-dependent Cl- /HCO3 - exchange. This exchange is stimulated by angiotensin II administration and is also stimulated in models of metabolic alkalosis, for instance after aldosterone or NaHCO3 administration. In some rodent models, pendrin-mediated HCO3 - secretion modulates acid-base balance...
December 2017: Kidney Research and Clinical Practice
https://www.readbyqxmd.com/read/29251736/pge-2-ep-1-receptor-inhibits-vasopressin-dependent-water-reabsorption-and-sodium-transport-in-mouse-collecting-duct
#14
Rania Nasrallah, Joseph Zimpelmann, David Eckert, Jamie Ghossein, Sean Geddes, Jean-Claude Beique, Jean-Francois Thibodeau, Chris R J Kennedy, Kevin D Burns, Richard L Hébert
PGE2 regulates glomerular hemodynamics, renin secretion, and tubular transport. This study examined the contribution of PGE2 EP1 receptors to sodium and water homeostasis. Male EP1-/- mice were bred with hypertensive TTRhRen mice (Htn) to evaluate blood pressure and kidney function at 8 weeks of age in four groups: wildtype (WT), EP1-/-, Htn, HtnEP1-/-. Blood pressure and water balance were unaffected by EP1 deletion. COX1 and mPGE2 synthase were increased and COX2 was decreased in mice lacking EP1, with increases in EP3 and reductions in EP2 and EP4 mRNA throughout the nephron...
March 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/29212817/casr-signaling-down-regulates-aqp2-expression-via-a-novel-microrna-pathway-in-pendrin-and-nacl-cotransporter-knockout-mice
#15
Marianna Ranieri, Kamyar Zahedi, Grazia Tamma, Mariangela Centrone, Annarita Di Mise, Manoocher Soleimani, Giovanna Valenti
High concentrations of urinary calcium counteract vasopressin action via the activation of the calcium-sensing receptor (CaSR) that is expressed in the luminal membrane of collecting duct cells, which impairs the trafficking of aquaporin-2 (AQP2). Pendrin/NaCl cotransporter double-knockout (dKO) mice display significant calcium wasting and develop severe volume depletion, despite increased circulating vasopressin levels. We hypothesized that the CaSR-mediated impairment of AQP2 expression/trafficking underlies vasopressin resistance in dKO mice...
January 5, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29187856/a-role-for-iodide-and-thyroglobulin-in-modulating-the-function-of-human-immune-cells
#16
Mahmood Y Bilal, Svetlana Dambaeva, Joanne Kwak-Kim, Alice Gilman-Sachs, Kenneth D Beaman
Iodine is an essential element required for the function of all organ systems. Although the importance of iodine in thyroid hormone synthesis and reproduction is well known, its direct effects on the immune system are elusive. Human leukocytes expressed mRNA of iodide transporters (NIS and PENDRIN) and thyroid-related proteins [thyroglobulin (TG) and thyroid peroxidase (TPO)]. The mRNA levels of PENDRIN and TPO were increased whereas TG transcripts were decreased post leukocyte activation. Flow cytometric analysis revealed that both PENDRIN and NIS were expressed on the surface of leukocyte subsets with the highest expression occurring on monocytes and granulocytes...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29169695/immunohistochemical-analysis-of-the-distribution-of-molecules-involved-in-ionic-and-ph-regulation-in-the-lancelet-branchiostoma-floridae-hubbs-1922
#17
Ivan Cuoghi, Clara Lazzaretti, Mauro Mandrioli, Lucrezia Mola, Aurora Pederzoli
The aim of present work is to analyse the distribution of carbonic anhydrase II (CAII), cystic fibrosis transmembrane regulator (CFTR), vacuolar-type H+ -ATPase (V-H+ -ATPase), Na+ /K+ ATPase, Na+ /H+ exchanger (NHE) and SLC26A6 (solute carrier family 26, member 6), also known as pendrin protein, in the lancelet Branchiostoma floridae in order to go in depth in the evolution of osmoregulation and pH regulation in Chordates. In view of their phylogenetic position, lancelets may indeed provide a critical point of reference for studies on osmoregulation evolution in Chordates...
January 2018: Acta Histochemica
https://www.readbyqxmd.com/read/29089413/transcriptomes-of-major-renal-collecting-duct-cell-types-in-mouse-identified-by-single-cell-rna-seq
#18
Lihe Chen, Jae Wook Lee, Chung-Lin Chou, Anil V Nair, Maria A Battistone, Teodor G Păunescu, Maria Merkulova, Sylvie Breton, Jill W Verlander, Susan M Wall, Dennis Brown, Maurice B Burg, Mark A Knepper
Prior RNA sequencing (RNA-seq) studies have identified complete transcriptomes for most renal epithelial cell types. The exceptions are the cell types that make up the renal collecting duct, namely intercalated cells (ICs) and principal cells (PCs), which account for only a small fraction of the kidney mass, but play critical physiological roles in the regulation of blood pressure, extracellular fluid volume, and extracellular fluid composition. To enrich these cell types, we used FACS that employed well-established lectin cell surface markers for PCs and type B ICs, as well as a newly identified cell surface marker for type A ICs, c-Kit...
November 14, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29021385/aldosterone-is-essential-for-angiotensin-ii-induced-upregulation-of-pendrin
#19
Daigoro Hirohama, Nobuhiro Ayuzawa, Kohei Ueda, Mitsuhiro Nishimoto, Wakako Kawarazaki, Atsushi Watanabe, Tatsuo Shimosawa, Takeshi Marumo, Shigeru Shibata, Toshiro Fujita
The renin-angiotensin-aldosterone system has an important role in the control of fluid homeostasis and BP during volume depletion. Dietary salt restriction elevates circulating angiotensin II (AngII) and aldosterone levels, increasing levels of the Cl- /HCO3 - exchanger pendrin in β -intercalated cells and the Na+ -Cl- cotransporter (NCC) in distal convoluted tubules. However, the independent roles of AngII and aldosterone in regulating these levels remain unclear. In C57BL/6J mice receiving a low-salt diet or AngII infusion, we evaluated the membrane protein abundance of pendrin and NCC; assessed the phosphorylation of the mineralocorticoid receptor, which selectively inhibits aldosterone binding in intercalated cells; and measured BP by radiotelemetry in pendrin-knockout and wild-type mice...
January 2018: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28955955/human-slc26a4-pendrin-stas-domain-is-a-nucleotide-binding-protein-refolding-and-characterization-for-structural-studies
#20
Alok K Sharma, Tobias Krieger, Alan C Rigby, Israel Zelikovic, Seth L Alper
Mutations in the human SLC26A4/Pendrin polypeptide (hPDS) cause Pendred Syndrome /DFNB4, syndromic deafness with enlargement of the vestibular aqueduct and low-penetrance goiter. Here we present data on cloning, protein overexpression and purification, refolding, and biophysical characterization of the recombinant hPDS STAS domain lacking its intrinsic variable sequence (STAS-ΔIVS). We report a reproducible protein refolding protocol enabling milligram scale expression and purification of uniformly (15)N- and (13)C(/15)N-enriched hPDS STAS-ΔIVS domain suitable for structural characterization by solution NMR...
December 2016: Biochemistry and Biophysics Reports
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