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https://www.readbyqxmd.com/read/28803436/acute-regulated-expression-of-pendrin-in-human-urinary-exosomes
#1
Ganesh Pathare, Nasser Dhayat, Nilufar Mohebbi, Carsten A Wagner, Lydie Cheval, Thomas J Neuhaus, Daniel G Fuster
It is well known that pendrin, an apical Cl(-)/HCO3(-)exchanger in type B intercalated cells, is modulated by chronic acid-base disturbances and electrolyte intake. To study this adaptation further at the acute level, we analyzed urinary exosomes from individuals subjected to oral acute acid, alkali, and NaCl loading. Acute oral NH4Cl loading (n = 8) elicited systemic acidemia with a drop in urinary pH and an increase in urinary NH4 excretion. Nadir urinary pH was achieved 5 h after NH4Cl loading. Exosomal pendrin abundance was dramatically decreased at 3 h after acid loading...
August 12, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28771454/%C3%AE-ketoglutarate-drives-electroneutral-nacl-reabsorption-in-intercalated-cells-by-activating-a-g-protein-coupled-receptor-oxgr1
#2
Paul R Grimm, Paul A Welling
PURPOSE OF REVIEW: This review describes the recent discoveries about a powerful electroneutral NaCl reabsorption mechanism in intercalated cells, and its regulation by an intrarenal metabolite paracrine, α-ketoglutartate, and the G-protein coupled receptor, Oxgr1. RECENT FINDINGS: The distal nephron fine-tunes sodium, chloride, potassium, hydrogen, bicarbonate and water transport to maintain electrolyte homeostasis and blood pressure. Intercalated cells have been traditionally viewed as the professional regulators of acid-base balance, but recent studies reveal that a specific population of intercalated cells, identified by the pendrin-transporter, have a surprising role in the regulation of salt balance...
September 2017: Current Opinion in Nephrology and Hypertension
https://www.readbyqxmd.com/read/28750403/ablation-of-the-cl-hco3-exchanger-pendrin-enhances-hydrochlorothiazide-induced-diuresis
#3
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/28719636/the-non-diuretic-hypotensive-effects-of-thiazides-are-enhanced-during-volume-depletion-states
#4
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/28718179/genetic-alterations-in-pendrin-slc26a4-gene-in-adult-hypothyroid-patients
#5
Sourav Mukherjee, Manalee Guha, Bidisha Adhikary, Biswabandhu Bankura, Pubali Mitra, Subhankar Chowdhury, Madhusudan Das
Current study was aimed to screen the SLC26A4 gene in 127 nonautoimmune and noncongenital hypothyroid patients, who were under optimal iodine nutrition and devoid of any characteristics of Pendred syndrome from eastern part of Indian population. 8 single nucleotide variants/mutations were identified in heterozygous state in 20% patient population, which include 1 novel nonsynonymous (p.C18S), 1 novel intronic (g.942C>A), 3 known nonsynonymous (p.S23X, p.V239D, and p.I455F), and 3 known intronic (g.23034G>T, g...
September 2017: Hormone and Metabolic Research, Hormon- und Stoffwechselforschung, Hormones et Métabolisme
https://www.readbyqxmd.com/read/28648509/pendred-syndrome
#6
REVIEW
Jean-Louis Wémeau, Peter Kopp
Pendred syndrome is an autosomal recessive disorder that is classically defined by the combination of sensorineural deafness/hearing impairment, goiter, and an abnormal organification of iodide with or without hypothyroidism. The hallmark of the syndrome is the impaired hearing, which is associated with inner ear malformations such as an enlarged vestibular aqueduct (EVA). The thyroid phenotype is variable and may be modified by the nutritional iodine intake. Pendred syndrome is caused by biallelic mutations in the SLC26A4/PDS gene, which encodes the multifunctional anion exchanger pendrin...
March 2017: Best Practice & Research. Clinical Endocrinology & Metabolism
https://www.readbyqxmd.com/read/28648508/iodide-handling-disorders-nis-tpo-tg-iyd
#7
REVIEW
Héctor M Targovnik, Cintia E Citterio, Carina M Rivolta
Iodide Handling Disorders lead to defects of the biosynthesis of thyroid hormones (thyroid dyshormonogenesis, TD) and thereafter congenital hypothyroidism (CH), the most common endocrine disease characterized by low levels of circulating thyroid hormones. The prevalence of CH is 1 in 2000-3000 live births. Prevention of CH is based on prenatal diagnosis, carrier identification, and genetic counseling. In neonates a complete diagnosis of TD should include clinical examination, biochemical thyroid tests, thyroid ultrasound, radioiodine or technetium scintigraphy and perchlorate discharge test (PDT)...
March 2017: Best Practice & Research. Clinical Endocrinology & Metabolism
https://www.readbyqxmd.com/read/28560800/emerging-targets-of-diuretic-therapy
#8
REVIEW
C-J Cheng, A R Rodan, C-L Huang
Diuretics are commonly prescribed for treatment in patients with hypertension, edema, or heart failure. Studies on hypertensive and salt-losing disorders and on urea transporters have contributed to better understanding of mechanisms of renal salt and water reabsorption and their regulation. Proteins involved in the regulatory pathways are emerging targets for diuretic and aquaretic therapy. Integrative high-throughput screening, protein structure analysis, and chemical modification have identified promising agents for preclinical testing in animals...
September 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28378089/interleukin-13-increases-pendrin-abundance-to-the-cell-surface-in-bronchial-nci-h292-cells-via-rho-actin-signaling
#9
Annamaria Russo, Marianna Ranieri, Annarita Di Mise, Silvia Dossena, Tommaso Pellegrino, Emilia Furia, Charity Nofziger, Lucantonio Debellis, Markus Paulmichl, Giovanna Valenti, Grazia Tamma
Interleukin-13 (IL13) is a major player in the development of airway hyperresponsiveness in several respiratory disorders. Emerging data suggest that an increased expression of pendrin in airway epithelia is associated with elevated airway hyperreactivity in asthma. Here, we investigate the effect of IL13 on pendrin localization and function using bronchiolar NCI-H292 cells. The data obtained revealed that IL13 increases the cell surface expression of pendrin. This effect was paralleled by a significant increase in the intracellular pH, possibly via indirect stimulation of NHE...
April 4, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28365704/interleukin-4-induces-cpg-site-specific-demethylation-of-the-pendrin-promoter-in-primary-human-bronchial-epithelial-cells
#10
Giada Scantamburlo, Simone Vanoni, Silvia Dossena, Selma M Soyal, Emanuele Bernardinelli, Davide Antonio Civello, Wolfgang Patsch, Markus Paulmichl, Charity Nofziger
Pendrin is upregulated in bronchial epithelial cells following IL-4 stimulation via binding of STAT6 to an N4 GAS motif. Basal CpG methylation of the pendrin promoter is cell-specific. We studied if a correlation exists between IL-4 sensitivity and the CpG methylation status of the pendrin promoter in human bronchial epithelial cell models. METHODS: Real-time PCR and pyrosequencing were used to respectively quantify pendrin mRNA levels and methylation of pendrin promoter, with and without IL-4 stimulation, in healthy and diseased primary HBE cells, as well as NCI-H292 cells...
2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28341401/discovery-of-2-aminophenyl-methanol-as-a-new-molecular-chaperone-that-rescues-the-localization-of-p123s-mutant-pendrin-stably-expressed-in-hek293-cells
#11
Wataru Nabeyama, Kenji Ishihara, Hyun Seung Ban, Hiroshi Wada, Hiroyuki Nakamura
Pendred syndrome is the most common form of syndromic deafness. It is associated with a mutation in the SLC26A4 gene that encodes pendrin, which is thought to maintain the ion concentration of endolymph in the inner ear most likely by acting as a chloride/bicarbonate transporter. Mutations in the SLC26A4 gene are responsible for sensorineural hearing loss. In this study, we established a stable HEK293 cell line expressing P123S mutant pendrin and developed screening methods for compounds that show pharmacological chaperone activity by image analysis using CellInsight™...
March 14, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28289181/hypokalemia-and-pendrin-induction-by-aldosterone
#12
Ning Xu, Daigoro Hirohama, Kenichi Ishizawa, Wen Xiu Chang, Tatsuo Shimosawa, Toshiro Fujita, Shunya Uchida, Shigeru Shibata
Aldosterone plays an important role in regulating Na-Cl reabsorption and blood pressure. Epithelial Na(+) channel, Na(+)-Cl(-) cotransporter, and Cl(-)/HCO3(-) exchanger pendrin are the major mediators of Na-Cl transport in the aldosterone-sensitive distal nephron. Existing evidence also suggests that plasma K(+) concentration affects renal Na-Cl handling. In this study, we posited that hypokalemia modulates the effects of aldosterone on pendrin in hyperaldosteronism. Chronic aldosterone infusion in mice increased pendrin levels at the plasma membrane, and correcting hypokalemia in this model almost completely blocked pendrin upregulation...
May 2017: Hypertension
https://www.readbyqxmd.com/read/28108829/vascular-contractile-reactivity-in-hypotension-due-to-reduced-renal-reabsorption-of-na-and-restricted-dietary-na
#13
Saeed Alshahrani, Robert M Rapoport, Manoocher Soleimani
Reduced renal Na(+) reabsorption along with restricted dietary Na(+) depletes intravascular plasma volume which can then result in hypotension. Whether hypotension occurs and the magnitude of hypotension depends in part on compensatory angiotensin II-mediated increased vascular resistance. We investigated whether the ability of vascular resistance to mitigate the hypotension was compromised by decreased contractile reactivity. In vitro reactivity was investigated in aorta from mouse models of reduced renal Na(+) reabsorption and restricted dietary Na(+) associated with considerable hypotension and renin-angiotensin system activation: (1) the Na(+)-Cl(-)-Co-transporter (NCC) knockout (KO) with Na(+) restricted diet (0...
March 2017: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/28103777/role-of-iodine-in-metabolism
#14
Szybiński Zbigniew
The natural resources of iodine are seawater, seaweeds and saltpeter-nitrate deposits in Chile. Over 1/3 of the global population is exposed to iodine deficiency, especially in the mountains. Iodine is a component of the thyroid hormones and a strong antioxidant with electric potential of -0.54 V. Iodine as iodide is taken up by the thyroid gland, gastric mucosa, salivary glands and mammary glands in pregnant and breast-feeding women. The transport of iodine to the thyroid gland is regulated by specific enzymes: Natrium-Iodine Symporter, Na+/K+ATP-ase, Pendrin and Apical Iodine Transporter...
January 19, 2017: Recent Patents on Endocrine, Metabolic & Immune Drug Discovery
https://www.readbyqxmd.com/read/28064162/acute-genetic-ablation-of-pendrin-lowers-blood-pressure-in-mice
#15
Francesco Trepiccione, Christelle Soukaseum, Veronique Baudrie, Yusuke Kumai, Jacques Teulon, Bruno Villoutreix, Nicolas Cornière, Philine Wangemann, Andrew J Griffith, Yoon Byung Choi, Juliette Hadchouel, Regine Chambrey, Dominique Eladari
Background: Pendrin, the chloride/bicarbonate exchanger of β-intercalated cells of the renal connecting tubule and the collecting duct, plays a key role in NaCl reabsorption by the distal nephron. Therefore, pendrin may be important for the control of extracellular fluid volume and blood pressure. Methods: Here, we have used a genetic mouse model in which the expression of pendrin can be switched-on in vivo by the administration of doxycycline. Pendrin can also be rapidly removed when doxycycline administration is discontinued...
July 1, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28052261/cochlear-cell-modeling-using-disease-specific-ipscs-unveils-a-degenerative-phenotype-and-suggests-treatments-for-congenital-progressive-hearing-loss
#16
Makoto Hosoya, Masato Fujioka, Takefumi Sone, Satoshi Okamoto, Wado Akamatsu, Hideki Ukai, Hiroki R Ueda, Kaoru Ogawa, Tatsuo Matsunaga, Hideyuki Okano
Hearing impairments are the most common symptom of congenital defects, and they generally remain intractable to treatment. Pendred syndrome, the most frequent syndromic form of hereditary hearing loss, is associated with mutations in the anion exchanger pendrin. Loss of pendrin function as an anion exchanger is thought to be causative, but rodent models do not exhibit progressive deafness. Here, we report a degenerative phenotype exhibiting mutant pendrin aggregates and increased susceptibility to cellular stresses in cochlear epithelial cells induced from patient-derived induced pluripotent stem cells (iPSCs)...
January 3, 2017: Cell Reports
https://www.readbyqxmd.com/read/28043731/acetazolamide-and-hydrochlorothiazide-followed-by-furosemide-versus-furosemide-and-hydrochlorothiazide-followed-by-furosemide-for-the-treatment-of-adults-with-nephrotic-edema-a-randomized-trial
#17
RANDOMIZED CONTROLLED TRIAL
Mohammad Amin Fallahzadeh, Banafshe Dormanesh, Mohammad Kazem Fallahzadeh, Jamshid Roozbeh, Mohammad Hossein Fallahzadeh, Mohammad Mahdi Sagheb
BACKGROUND: Nephrotic edema is considered refractory if it does not respond to maximum or near-maximum doses of loop diuretics. This condition can be treated with loop diuretics and thiazides. However, animal studies show that the simultaneous downregulation of pendrin with acetazolamide and inhibition of the sodium-chloride cotransporter with hydrochlorothiazide generates significant diuresis, and furosemide administration following a pendrin inhibitor potentiates furosemide's diuretic effect...
March 2017: American Journal of Kidney Diseases: the Official Journal of the National Kidney Foundation
https://www.readbyqxmd.com/read/28013561/the-effect-of-smoking-on-placental-pendrin-expression
#18
Ahmet Karatas, Havva Erdem, Zehra Karatas, Tulay Ozlu, Bulent Cakmak
Pendrin is important for transport of iodine across the placenta. Thiocyanate coming from cigarette is a competitive inhibitor of iodine transport. We aimed to evaluate the pendrin immunostaining intensity in placentas of smoker and non-smoker women. Placental tissues from 61 women, of which 28 were in smoking, and 33 were in non-smoking group were evaluated by immunohistochemical staining. Positive immunostaining was evaluated using a semiquantitative score: 0, negative; +, mild; ++, moderate; and +++, intense...
December 25, 2016: Journal of Obstetrics and Gynaecology: the Journal of the Institute of Obstetrics and Gynaecology
https://www.readbyqxmd.com/read/27864363/induction-of-airway-allergic-inflammation-by-hypothiocyanite-via-epithelial-cells
#19
Shoichi Suzuki, Masahiro Ogawa, Shoichiro Ohta, Satoshi Nunomura, Yasuhiro Nanri, Hiroshi Shiraishi, Yasutaka Mitamura, Tomohito Yoshihara, James J Lee, Kenji Izuhara
Hypothiocyanite (OSCN(-)) serves as a potent innate defense system against microbes in the lungs. OSCN(-) is generated by the catalysis of peroxidases using thiocyanate transported via several anion transporters, including pendrin/SLC26A4 and hydrogen peroxide (H2O2) generated by Duox1 and Duox2. We previously demonstrated that expression of pendrin, peroxidases, and Duox1/Duox2 is up-regulated in bronchial asthma patients and/or asthma model mice and that these molecules are important in accelerating airway inflammation...
December 30, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27861301/a-novel-mutation-in-slc26a4-causes-nonsyndromic-autosomal-recessive-hearing-impairment
#20
Axel Wolf, Alexandra Frohne, Matthew Allen, Thomas Parzefall, Martin Koenighofer, Markus M Schreiner, Christian Schoefer, Klemens Frei, Trevor Lucas
BACKGROUND: Heterozygous mutations in GJB2 (MIM: 121011) encoding the gap junction protein connexin 26 are overrepresented in patient groups suffering from nonsyndromic sensorineural hearing impairment (HI) implying the involvement of additional genetic factors. Mutations in SLC26A4 (MIM: 605646), encoding the protein pendrin can cause both Pendred syndrome and autosomal recessive, nonsyndromic HI locus 4 type sensorineural HI (MIM: 600791). OBJECTIVES: Aim of this study was to investigate the role of SLC26A4 coding mutations in a nonsyndromic hearing impairment (NSHI) patient group bearing heterozygous GJB2 35delG mutations...
February 2017: Otology & Neurotology
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