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https://www.readbyqxmd.com/read/28819106/identification-and-characterization-of-a-bacterial-homolog-of-chloride-intracellular-channel-clic-protein
#1
Shubha Gururaja Rao, Devasena Ponnalagu, Sowmya Sukur, Harkewal Singh, Shridhar Sanghvi, Yixiao Mei, Ding J Jin, Harpreet Singh
Chloride intracellular channels (CLIC) are non-classical ion channels lacking a signal sequence for membrane targeting. In eukaryotes, they are implicated in cell volume regulation, acidification, and cell cycle. CLICs resemble the omega class of Glutathione S-transferases (GST), yet differ from them in their ability to form ion channels. They are ubiquitously found in eukaryotes but no prokaryotic homolog has been characterized. We found that indanyloxyacetic acid-94 (IAA-94), a blocker of CLICs, delays the growth of Escherichia coli...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28808008/mathematical-model-reveals-role-of-nucleotide-signaling-in-airway-surface-liquid-homeostasis-and-its-dysregulation-in-cystic-fibrosis
#2
Conner I Sandefur, Richard C Boucher, Timothy C Elston
Mucociliary clearance is composed of three components (i.e., mucin secretion, airway surface hydration, and ciliary-activity) which function coordinately to clear inhaled microbes and other foreign particles from airway surfaces. Airway surface hydration is maintained by water fluxes driven predominantly by active chloride and sodium ion transport. The ion channels that mediate electrogenic ion transport are regulated by extracellular purinergic signals that signal through G protein-coupled receptors. These purinoreceptors and the signaling pathways they activate have been identified as possible therapeutic targets for treating lung disease...
August 14, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28803966/a-chimeric-prokaryotic-eukaryotic-pentameric-ligand-gated-ion-channel-reveals-interactions-between-the-extracellular-and-transmembrane-domains-shape-neurosteroid-modulation
#3
Borna Ghosh, Tzu-Wei Tsao, Cynthia Czajkowski
Pentameric ligand-gated ion channels (pLGICs) are the targets of several clinical and endogenous allosteric modulators including anesthetics and neurosteroids. Molecular mechanisms underlying allosteric drug modulation are poorly understood. Here, we constructed a chimeric pLGIC by fusing the extracellular domain (ECD) of the proton-activated, cation-selective bacterial channel GLIC to the transmembrane domain (TMD) of the human ρ1 chloride-selective GABAAR, and tested the hypothesis that drug actions are regulated locally in the domain that houses its binding site...
August 10, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28802235/steviol-stabilizes-polycystin-1-expression-and-promotes-lysosomal-degradation-of-cftr-and-%C3%AE-catenin-proteins-in-renal-epithelial-cells
#4
Chaowalit Yuajit, Chatchai Muanprasat, Sureeporn Homvisasevongsa, Varanuj Chatsudthipong
Malfunction of polycystin 1 (PC1) is linked to abnormally high epithelial cell proliferation and fluid secretion, eventually leading to renal cyst development and declined renal function as found in autosomal dominant polycystic kidney disease (ADPKD). Currently, there is no effective therapy for ADPKD. Recent studies report PC1 regulates CFTR chloride channels and β-catenin levels in normal renal epithelial cells. Concurrently, our previous study found steviol retarded renal cyst enlargement in an in vitro and in an in vivo models by reducing CFTR expression and activity...
August 9, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28798690/risk-of-myopathy-in-patients-in-therapy-with-statins-identification-of-biological-markers-in-a-pilot-study
#5
Giulia M Camerino, Olimpia Musumeci, Elena Conte, Kejla Musaraj, Adriano Fonzino, Emanuele Barca, Marco Marino, Carmelo Rodolico, Domenico Tricarico, Claudia Camerino, Maria R Carratù, Jean-François Desaphy, Annamaria De Luca, Antonio Toscano, Sabata Pierno
Statin therapy may induce skeletal muscle damage ranging from myalgia to severe rhabdomyolysis. Our previous preclinical studies showed that statin treatment in rats involves the reduction of skeletal muscle ClC-1 chloride channel expression and related chloride conductance (gCl). An increase of the activity of protein kinase C theta (PKC theta) isoform, able to inactivate ClC-1, may contribute to destabilize sarcolemma excitability. These effects can be detrimental for muscle function leading to drug-induced myopathy...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28798480/magnesium-chloride-promotes-osteogenesis-through-notch-signaling-activation-and-expansion-of-mesenchymal-stem-cells
#6
Juan M Díaz-Tocados, Carmen Herencia, Julio M Martínez-Moreno, Addy Montes de Oca, Maria E Rodríguez-Ortiz, Noemi Vergara, Alfonso Blanco, Sonja Steppan, Yolanda Almadén, Mariano Rodríguez, Juan R Muñoz-Castañeda
Mesenchymal stem cells (MSC) are osteoblasts progenitors and a variety of studies suggest that they may play an important role for the health in the field of bone regeneration. Magnesium supplementation is gaining importance as adjuvant treatment to improve osteogenesis, although the mechanisms involving this process are not well understood. The objective of this study was to investigate the effects of magnesium on MSC differentiation. Here we show that in rat bone marrow MSC, magnesium chloride increases MSC proliferation in a dose-dependent manner promoting osteogenic differentiation and mineralization...
August 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28798394/orthosteric-versus-allosteric-dependent-activation-of-the-gabaa-receptor-requires-numerically-distinct-subunit-level-rearrangements
#7
Jahanshah Amin, Meena S Subbarayan
Anaesthetic molecules act on synaptic transmission via the allosteric modulation of ligand-gated chloride channels, such as hetero-oligomeric α1β2γ2 GABAA receptors. To elucidate the overall activation paradigm via allosteric versus orthosteric sites, we used highly homologous, but homo-oligomeric, ρ1 receptors that are contrastingly insensitive to anaesthetics and respond partially to several full GABA α1β2γ2 receptor agonists. Here, we coexpressed varying ratios of RNAs encoding the wild-type and the mutated ρ1 subunits, which are anaesthetic-sensitive and respond with full efficacy to partial GABA agonists, to generate distinct ensembles of receptors containing five, four, three, two, one, or zero mutated subunits...
August 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28796813/a-novel-organotypic-3d-sweat-gland-model-with-physiological-functionality
#8
Patricia Klaka, Sabine Grüdl, Bernhard Banowski, Melanie Giesen, Andrea Sättler, Peter Proksch, Thomas Welss, Thomas Förster
Dysregulated human eccrine sweat glands can negatively impact the quality-of-life of people suffering from disorders like hyperhidrosis. Inability of sweating can even result in serious health effects in humans affected by anhidrosis. The underlying mechanisms must be elucidated and a reliable in vitro test system for drug screening must be developed. Here we describe a novel organotypic three-dimensional (3D) sweat gland model made of primary human eccrine sweat gland cells. Initial experiments revealed that eccrine sweat gland cells in a two-dimensional (2D) culture lose typical physiological markers...
2017: PloS One
https://www.readbyqxmd.com/read/28775266/in-silico-model-of-the-human-clc-kb-chloride-channel-pore-mapping-biostructural-pathology-and-drug-screening
#9
Maxime Louet, Sara Bitam, Naziha Bakouh, Yohan Bignon, Gabrielle Planelles, David Lagorce, Maria A Miteva, Dominique Eladari, Jacques Teulon, Bruno O Villoutreix
The human ClC-Kb channel plays a key role in exporting chloride ions from the cytosol and is known to be involved in Bartter syndrome type 3 when its permeation capacity is decreased. The ClC-Kb channel has been recently proposed as a potential therapeutic target to treat hypertension. In order to gain new insights into the sequence-structure-function relationships of this channel, to investigate possible impacts of amino-acid substitutions, and to design novel inhibitors, we first built a structural model of the human ClC-Kb channel using comparative modeling strategies...
August 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28775098/influenza-virus-infection-alters-ion-channel-function-of-airway-and-alveolar-cells-mechanisms-and-physiological-sequelae
#10
James D Londino, Ahmed Lazrak, James F Collawn, Zsuzsanna Bebok, Kevin S Harrod, Sadis Matalon
The cystic fibrosis transmembrane conductance regulator (CFTR) and the amiloride-sensitive epithelial sodium channels (ENaC) are located in the apical membranes of airway and alveolar epithelial cells. These transporters play an important role in the regulation of lung fluid balance across airway and alveolar epithelia by being the conduits for chloride (Cl(-)) and bicarbonate (HCO3(-)) secretion and sodium (Na(+)) ion absorption, respectively. The functional role of these channels in the respiratory tract is to maintain the optimum volume and ionic composition of the bronchial pericilary fluid (PCL) and alveolar lining fluid (ALF) layers...
August 3, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28774558/molecular-dynamics-of-the-cryo-em-cftr-structure
#11
Hedvig Tordai, Ibolya Leveles, Tamás Hegedűs
Cystic fibrosis (CF), a lethal monogenic disease, is caused by mutant variants of the CF transmembrane conductance regulator (CFTR). Recent advances in single molecule cryo-EM methods enabled structural determination of full-length human and zebrafish CFTR, achieving an important milestone for CF drug development. To relate these structures to the gating cycle, we examined its dynamic features using molecular dynamics simulations. Our results show that the nucleotide binding domains (NBDs) in this bottom-open apo conformation exhibit motions related to dimerization and the bottom-closed apo CFTR model indicates opening of NBDs in contrast to transporters...
July 31, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28774085/tribocorrosion-failure-mechanism-of-tin-siox-duplex-coating-deposited-on-aisi304-stainless-steel
#12
Qiang Chen, Zhiwen Xie, Tian Chen, Feng Gong
TiN/SiOx duplex coatings were synthesized on AISI304 stainless steel by plasma immersion ion implantation and deposition (PIIID) followed by radio frequency magnetron sputtering (RFMS). The microstructure and tribocorrosion failure behaviors of the duplex coatings were investigated by X-ray diffraction, X-ray photoelectron spectroscopy, scanning electron microscopy, atomic force microscopy, reciprocating-sliding tribometer, and electrochemical tests. The as-deposited duplex coating had a two-layered columnar growth structure consisting of face-centered cubic TiN and amorphous SiOx...
November 26, 2016: Materials
https://www.readbyqxmd.com/read/28772848/effect-of-the-cationic-block-structure-on-the-characteristics-of-sludge-flocs-formed-by-charge-neutralization-and-patching
#13
Huaili Zheng, Li Feng, Baoyu Gao, Yuhao Zhou, Shixin Zhang, Bingchen Xu
In this study, a template copolymer (TPAA) of (3-Acrylamidopropyl) trimethylammonium chloride (AATPAC) and acrylamide (AM) was successfully synthesized though ultrasonic-initiated template copolymerization (UTP), using sodium polyacrylate (PAAS) as a template. TPAA was characterized by an evident cationic microblock structure which was observed through the analyses of the reactivity ratio, Fourier transform infrared spectroscopy (FTIR), ¹H ((13)C) nuclear magnetic resonance spectroscopy (¹H ((13)C) NMR), and thermogravimetry/differential scanning calorimetry (TG/DSC)...
May 3, 2017: Materials
https://www.readbyqxmd.com/read/28765511/nitrate-reductase-knockout-uncouples-nitrate-transport-from-nitrate-assimilation-and-drives-repartitioning-of-carbon-flux-in-a-model-pennate-diatom
#14
James Kevin McCarthy, Sarah R Smith, John P McCrow, Maxine Tan, Hong Zheng, Karen Beeri, Robyn A Roth, Christiane Lichtle, Ursula Goodenough, Chris Bowler, Cristopher L Dupont, Andrew E Allen
The ecological prominence of diatoms in the ocean environment largely results from their superior competitive ability for dissolved nitrate (NO3-). To investigate the cellular and genetic basis of diatom NO3- assimilation, we generated a knockout in the nitrate reductase gene (NR-KO) of the model pennate diatom Phaeodactylum tricornutum. In NR-KO cells, N assimilation was abolished although NO3-transport remained intact. Unassimilated NO3- accumulated in NR-KO cells, resulting in swelling and associated changes in biochemical composition and physiology...
August 1, 2017: Plant Cell
https://www.readbyqxmd.com/read/28754990/assessments-of-iodoindoles-and-abamectin-as-inducers-of-methuosis-in-pinewood-nematode-bursaphelenchus-xylophilus
#15
Satish Kumar Rajasekharan, Jin-Hyung Lee, Vinothkannan Ravichandran, Jintae Lee
Bursaphelenchus xylophilus is a quarantined migratory endoparasite known to cause severe economic losses in pine forest ecosystems. The study presents the nematicidal effects of halogenated indoles on B. xylophilus and their action mechanisms. 5-Iodoindole and abamectin (positive control) at low concentration (10 µg/mL) presented similar and high nematicidal activities against B. xylophilus. 5-Iodoindole diminished fecundity, reproductive activities, embryonic and juvenile lethality and locomotor behaviors...
July 28, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28748751/update-on-nitazoxanide-a-multifunctional-chemotherapeutic-agent
#16
Anshul Shakya, Hans Raj Bhat, Surjit Kumar Ghosh
Background: The thiazolide nitazoxanide (NTZ) is a broad-spectrum anti-infective drug that adversely affects viability, growth, and proliferation of a range of extracellular and intracellular protozoan, helminths, anaerobic and microaerophilic bacteria, and viruses. Methods: Current review compiled the potential chemotherapeutic efficacy of NTZ against a variety of such disease-causing macro and/or micro-organisms as well as neoplastic cells, using various search engines viz...
July 27, 2017: Current Drug Discovery Technologies
https://www.readbyqxmd.com/read/28743606/the-botanical-drug-substance-crofelemer-as-a-model-system-for-comparative-characterization-of-complex-mixture-drugs
#17
Peter A Kleindl, Jian Xiong, Asha Hewarathna, Olivier Mozziconacci, Maulik K Nariya, Adam C Fisher, Eric J Deeds, Sangeeta B Joshi, C Russell Middaugh, Christian Schöneich, David B Volkin, M Laird Forrest
Crofelemer is a botanical polymeric proanthocyanidin that inhibits chloride channel activity and is used clinically for treating HIV-associated secretory diarrhea. Crofelemer lots may exhibit significant physicochemical variation due to the natural source of the raw material. A variety of physical, chemical, and biological assays were utilized to identify potential critical quality attributes (CQAs) of crofelemer, which may be useful in characterizing differently sourced and/or processed drug products. Crofelemer drug substance was extracted from tablets of one commerical drug product lot, fractionated, and subjected to accelerated thermal degradation studies to produce derivative lots with variations in chemical and physical composition potentially representative of manufacturing and raw material variation...
July 22, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28739571/splice-variants-of-ph-sensitive-chloride-channel-identify-a-key-determinant-of-ivermectin-sensitivity-in-the-larvae-of-the-silkworm-bombyx-mori
#18
Daiki Okuhara, Shogo Furutani, Katsuhiko Ito, Makoto Ihara Ihara, Kazuhiko Matsuda
The pH-sensitive chloride channels (pHCls) are broadly expressed in insects, but little is known about their physiological role, diversity and sensitivity to insecticides acting on relevant chloride channels. Here we have sequenced 50 transcripts of the pHCl-1 gene from the brain, third thoracic ganglion (T3G) and midgut of larvae of silkworm Bombyx mori. It was found that >50 variants were expressed with distinct splicing in the T3G compared to the brain and midgut. Of the variants detected, variant 9, which was expressed most abundantly in the larvae, was reconstituted in Xenopus laevis oocytes to characterise its pH- and ivermectin sensitivity...
July 24, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28736919/a-g326e-substitution-in-the-glutamate-gated-chloride-channel-3-glucl3-of-the-two-spotted-spider-mite-tetranychus-urticae-abolishes-the-agonistic-activity-of-macrocyclic-lactones
#19
Catherine Mermans, Wannes Dermauw, Sven Geibel, Thomas Van Leeuwen
BACKGROUND: The macrocyclic lactones abamectin and milbemectin are frequently used to control phytophagous mites such as Tetranychus urticae. Consequently, resistance has developed and was genetically linked with substitutions in the glutamate-gated chloride channel (GluCl) subunits TuGluCl1 and TuGluCl3. Here, we functionally validated a G326E substitution in TuGluCl3 by functional expression in Xenopus laevis oocytes followed by two-electrode voltage-clamp electrophysiology. RESULTS: Homomeric wild-type and mutated GluCl3 were successfully expressed...
July 24, 2017: Pest Management Science
https://www.readbyqxmd.com/read/28736364/-angiotensin-1-7-protects-cardiac-myocytes-against-high-glucose-induced-injury-by-inhibiting-clc-3-chloride-channels
#20
Shao-Ai Ccai, Jing-Fu Chen, Mei-Ji Chen, Jian-Cong Lin, Jian-Qiang Feng, Kai Lin, Xi-Mei Zhi, Wei-Jie Zhang, Wen Wu
OBJECTIVE: To explore whether angiotensin-(1-7) [Ang-(1-7)] protects cardiac myocytes against high glucose (HG)-induced injury by inhibiting ClC-3 chloride channels. METHOD: H9c2 cardiac cells were exposed to 35 mmol/L glucose for 24 h to establish a cell injury model. The cells were treated with Ang-(1-7) or the inhibitor of chloride channel (NPPB) in the presence of HG for 24 h to observe the changes in HG-induced cell injury. Cell counter kit 8 (CCK-8) assay was used to test the cell viability, and the morphological changes of the apoptotic cells were detected using Hoechst 33258 staining and fluorescent microscopy...
July 20, 2017: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
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