The Concise Guide to PHARMACOLOGY 2015/16
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BRIEF COMMUNICATION www.jasn.org Renal Fanconi Syndrome and Hypophosphatemic Rickets in the Absence of Xenotropic and Polytropic Retroviral Receptor in the Nephron Camille Ansermet,* Matthias B. Moor,* Gabriel Centeno,* Muriel Auberson,* † † ‡ Dorothy Zhang Hu, Roland Baron, Svetlana Nikolaeva,* Barbara Haenzi,* | Natalya Katanaeva,* Ivan Gautschi,* Vladimir Katanaev,*§ Samuel Rotman, Robert Koesters,¶ †† Laurent Schild,* Sylvain Pradervand,** Olivier Bonny,* and Dmitri Firsov* BRIEF COMMUNICATION *Department of Pharmacology and Toxicology and **Genomic Technologies Facility, University of Lausanne, Lausanne, Switzerland; †Department of Oral Medicine, Infection, and Immunity, Harvard School of Dental Medicine, Boston, Massachusetts; ‡Institute of Evolutionary Physiology and Biochemistry, St. Petersburg, Russia; §School of Biomedicine, Far Eastern Federal University, Vladivostok, Russia; |Services of Pathology and ††Nephrology, Department of Medicine, University Hospital of Lausanne, Lausanne, Switzerland; and ¶Université Pierre et Marie Curie, Paris, France ABSTRACT Tight control of extracellular and intracellular inorganic phosphate (Pi) levels is crit- leaves.4 Most recently, Legati et al. have ical to most biochemical and physiologic processes. Urinary Pi is freely filtered at the shown an association between genetic kidney glomerulus and is reabsorbed in the renal tubule by the action of the apical polymorphisms in Xpr1 and primary fa- sodium-dependent phosphate transporters, NaPi-IIa/NaPi-IIc/Pit2. However, the milial brain calcification disorder.5 How- molecular identity of the protein(s) participating in the basolateral Pi efflux remains ever, the role of XPR1 in the maintenance unknown. Evidence has suggested that xenotropic and polytropic retroviral recep- of Pi homeostasis remains unknown. Here, tor 1 (XPR1) might be involved in this process. Here, we show that conditional in- we addressed this issue in mice deficient for activation of Xpr1 in the renal tubule in mice resulted in impaired renal Pi Xpr1 in the nephron. -
A Computational Approach for Defining a Signature of Β-Cell Golgi Stress in Diabetes Mellitus
Page 1 of 781 Diabetes A Computational Approach for Defining a Signature of β-Cell Golgi Stress in Diabetes Mellitus Robert N. Bone1,6,7, Olufunmilola Oyebamiji2, Sayali Talware2, Sharmila Selvaraj2, Preethi Krishnan3,6, Farooq Syed1,6,7, Huanmei Wu2, Carmella Evans-Molina 1,3,4,5,6,7,8* Departments of 1Pediatrics, 3Medicine, 4Anatomy, Cell Biology & Physiology, 5Biochemistry & Molecular Biology, the 6Center for Diabetes & Metabolic Diseases, and the 7Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202; 2Department of BioHealth Informatics, Indiana University-Purdue University Indianapolis, Indianapolis, IN, 46202; 8Roudebush VA Medical Center, Indianapolis, IN 46202. *Corresponding Author(s): Carmella Evans-Molina, MD, PhD ([email protected]) Indiana University School of Medicine, 635 Barnhill Drive, MS 2031A, Indianapolis, IN 46202, Telephone: (317) 274-4145, Fax (317) 274-4107 Running Title: Golgi Stress Response in Diabetes Word Count: 4358 Number of Figures: 6 Keywords: Golgi apparatus stress, Islets, β cell, Type 1 diabetes, Type 2 diabetes 1 Diabetes Publish Ahead of Print, published online August 20, 2020 Diabetes Page 2 of 781 ABSTRACT The Golgi apparatus (GA) is an important site of insulin processing and granule maturation, but whether GA organelle dysfunction and GA stress are present in the diabetic β-cell has not been tested. We utilized an informatics-based approach to develop a transcriptional signature of β-cell GA stress using existing RNA sequencing and microarray datasets generated using human islets from donors with diabetes and islets where type 1(T1D) and type 2 diabetes (T2D) had been modeled ex vivo. To narrow our results to GA-specific genes, we applied a filter set of 1,030 genes accepted as GA associated. -
Identification of Key Genes and Pathways Involved in Response To
Deng et al. Biol Res (2018) 51:25 https://doi.org/10.1186/s40659-018-0174-7 Biological Research RESEARCH ARTICLE Open Access Identifcation of key genes and pathways involved in response to pain in goat and sheep by transcriptome sequencing Xiuling Deng1,2†, Dong Wang3†, Shenyuan Wang1, Haisheng Wang2 and Huanmin Zhou1* Abstract Purpose: This aim of this study was to investigate the key genes and pathways involved in the response to pain in goat and sheep by transcriptome sequencing. Methods: Chronic pain was induced with the injection of the complete Freund’s adjuvant (CFA) in sheep and goats. The animals were divided into four groups: CFA-treated sheep, control sheep, CFA-treated goat, and control goat groups (n 3 in each group). The dorsal root ganglions of these animals were isolated and used for the construction of a cDNA= library and transcriptome sequencing. Diferentially expressed genes (DEGs) were identifed in CFA-induced sheep and goats and gene ontology (GO) enrichment analysis was performed. Results: In total, 1748 and 2441 DEGs were identifed in CFA-treated goat and sheep, respectively. The DEGs identi- fed in CFA-treated goats, such as C-C motif chemokine ligand 27 (CCL27), glutamate receptor 2 (GRIA2), and sodium voltage-gated channel alpha subunit 3 (SCN3A), were mainly enriched in GO functions associated with N-methyl- D-aspartate (NMDA) receptor, infammatory response, and immune response. The DEGs identifed in CFA-treated sheep, such as gamma-aminobutyric acid (GABA)-related DEGs (gamma-aminobutyric acid type A receptor gamma 3 subunit [GABRG3], GABRB2, and GABRB1), SCN9A, and transient receptor potential cation channel subfamily V member 1 (TRPV1), were mainly enriched in GO functions related to neuroactive ligand-receptor interaction, NMDA receptor, and defense response. -
Roles of the Ion Channel Nalcn in Neuronal Excitability Control
University of Pennsylvania ScholarlyCommons Publicly Accessible Penn Dissertations Fall 2009 ROLES OF THE ION CHANNEL NALCN IN NEURONAL EXCITABILITY CONTROL Boxun Lu University of Pennsylvania, [email protected] Follow this and additional works at: https://repository.upenn.edu/edissertations Part of the Cellular and Molecular Physiology Commons, and the Molecular and Cellular Neuroscience Commons Recommended Citation Lu, Boxun, "ROLES OF THE ION CHANNEL NALCN IN NEURONAL EXCITABILITY CONTROL" (2009). Publicly Accessible Penn Dissertations. 245. https://repository.upenn.edu/edissertations/245 This paper is posted at ScholarlyCommons. https://repository.upenn.edu/edissertations/245 For more information, please contact [email protected]. ROLES OF THE ION CHANNEL NALCN IN NEURONAL EXCITABILITY CONTROL Abstract The resting membrane potential (RMP) of a neuron is set by a complex balance between charged ions, ion channels and transporters. Many of the ion channels have been identified at the molecular level. Missing from the molecular identification has been the voltage-insensitive background sodium ‘‘leak’’ conductance that depolarizes the RMP from the equilibrium potential of potassium and provides a crucial contribution to neuronal excitability One candidate for the molecular identity of this conductance is the protein NALCN. NALCN is a previously uncharacterized orphan member in the sodium/calcium channel family. It is widely expressed in the nervous system. My thesis project was designed to uncover the properties of NALCN and to find its functional roles, especially its contribution to the neuronal excitability as an ion channel. I found that NALCN formed a voltage-insensitive background sodium leak conductance. Such a conductance was detected in hippocampal neurons cultured from the wild-type mice but not the NALCN- /- mutant mice with targted disruption in the NALCN gene. -
Structure and Function of Ion Channels Regulating Sperm Motility—An Overview
International Journal of Molecular Sciences Review Structure and Function of Ion Channels Regulating Sperm Motility—An Overview Karolina Nowicka-Bauer 1,* and Monika Szymczak-Cendlak 2 1 Department of Chemical Physics, Faculty of Chemistry, Adam Mickiewicz University in Pozna´n, 61-614 Poznan, Poland 2 Department of Animal Physiology and Development, Faculty of Biology, Adam Mickiewicz University in Pozna´n,61-614 Poznan, Poland; [email protected] * Correspondence: [email protected] Abstract: Sperm motility is linked to the activation of signaling pathways that trigger movement. These pathways are mainly dependent on Ca2+, which acts as a secondary messenger. The mainte- nance of adequate Ca2+ concentrations is possible thanks to proper concentrations of other ions, such as K+ and Na+, among others, that modulate plasma membrane potential and the intracellular pH. Like in every cell, ion homeostasis in spermatozoa is ensured by a vast spectrum of ion channels supported by the work of ion pumps and transporters. To achieve success in fertilization, sperm ion channels have to be sensitive to various external and internal factors. This sensitivity is provided by specific channel structures. In addition, novel sperm-specific channels or isoforms have been found with compositions that increase the chance of fertilization. Notably, the most significant sperm ion channel is the cation channel of sperm (CatSper), which is a sperm-specific Ca2+ channel required for the hyperactivation of sperm motility. The role of other ion channels in the spermatozoa, such as voltage-gated Ca2+ channels (VGCCs), Ca2+-activated Cl-channels (CaCCs), SLO K+ channels or voltage-gated H+ channels (VGHCs), is to ensure the activation and modulation of CatSper. -
Stem Cells and Ion Channels
Stem Cells International Stem Cells and Ion Channels Guest Editors: Stefan Liebau, Alexander Kleger, Michael Levin, and Shan Ping Yu Stem Cells and Ion Channels Stem Cells International Stem Cells and Ion Channels Guest Editors: Stefan Liebau, Alexander Kleger, Michael Levin, and Shan Ping Yu Copyright © 2013 Hindawi Publishing Corporation. All rights reserved. This is a special issue published in “Stem Cells International.” All articles are open access articles distributed under the Creative Com- mons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Editorial Board Nadire N. Ali, UK Joseph Itskovitz-Eldor, Israel Pranela Rameshwar, USA Anthony Atala, USA Pavla Jendelova, Czech Republic Hannele T. Ruohola-Baker, USA Nissim Benvenisty, Israel Arne Jensen, Germany D. S. Sakaguchi, USA Kenneth Boheler, USA Sue Kimber, UK Paul R. Sanberg, USA Dominique Bonnet, UK Mark D. Kirk, USA Paul T. Sharpe, UK B. Bunnell, USA Gary E. Lyons, USA Ashok Shetty, USA Kevin D. Bunting, USA Athanasios Mantalaris, UK Igor Slukvin, USA Richard K. Burt, USA Pilar Martin-Duque, Spain Ann Steele, USA Gerald A. Colvin, USA EvaMezey,USA Alexander Storch, Germany Stephen Dalton, USA Karim Nayernia, UK Marc Turner, UK Leonard M. Eisenberg, USA K. Sue O’Shea, USA Su-Chun Zhang, USA Marina Emborg, USA J. Parent, USA Weian Zhao, USA Josef Fulka, Czech Republic Bruno Peault, USA Joel C. Glover, Norway Stefan Przyborski, UK Contents Stem Cells and Ion Channels, Stefan Liebau, -
Ion Channels
UC Davis UC Davis Previously Published Works Title THE CONCISE GUIDE TO PHARMACOLOGY 2019/20: Ion channels. Permalink https://escholarship.org/uc/item/1442g5hg Journal British journal of pharmacology, 176 Suppl 1(S1) ISSN 0007-1188 Authors Alexander, Stephen PH Mathie, Alistair Peters, John A et al. Publication Date 2019-12-01 DOI 10.1111/bph.14749 License https://creativecommons.org/licenses/by/4.0/ 4.0 Peer reviewed eScholarship.org Powered by the California Digital Library University of California S.P.H. Alexander et al. The Concise Guide to PHARMACOLOGY 2019/20: Ion channels. British Journal of Pharmacology (2019) 176, S142–S228 THE CONCISE GUIDE TO PHARMACOLOGY 2019/20: Ion channels Stephen PH Alexander1 , Alistair Mathie2 ,JohnAPeters3 , Emma L Veale2 , Jörg Striessnig4 , Eamonn Kelly5, Jane F Armstrong6 , Elena Faccenda6 ,SimonDHarding6 ,AdamJPawson6 , Joanna L Sharman6 , Christopher Southan6 , Jamie A Davies6 and CGTP Collaborators 1School of Life Sciences, University of Nottingham Medical School, Nottingham, NG7 2UH, UK 2Medway School of Pharmacy, The Universities of Greenwich and Kent at Medway, Anson Building, Central Avenue, Chatham Maritime, Chatham, Kent, ME4 4TB, UK 3Neuroscience Division, Medical Education Institute, Ninewells Hospital and Medical School, University of Dundee, Dundee, DD1 9SY, UK 4Pharmacology and Toxicology, Institute of Pharmacy, University of Innsbruck, A-6020 Innsbruck, Austria 5School of Physiology, Pharmacology and Neuroscience, University of Bristol, Bristol, BS8 1TD, UK 6Centre for Discovery Brain Science, University of Edinburgh, Edinburgh, EH8 9XD, UK Abstract The Concise Guide to PHARMACOLOGY 2019/20 is the fourth in this series of biennial publications. The Concise Guide provides concise overviews of the key properties of nearly 1800 human drug targets with an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. -
Nicotine Dependece
Alma Mater Studiorum – Università di Bologna DOTTORATO DI RICERCA IN Biologia Cellulare e Molecolare Ciclo XXX Settore Concorsuale: 05/I1 Settore Scientifico Disciplinare: BIO/18 GENETICA Investigation of genetic risk variants for nicotine dependence and cluster headache Presentata da: Cinzia Cameli Coordinatore Dottorato Supervisore Prof. Giovanni Capranico Prof.ssa Elena Maestrini Co-supervisore Dott.ssa Elena Bacchelli Esame finale anno 2018 TABLE OF CONTENTS ABSTRACT......................................................................................................................... 4 INTRODUCTION ................................................................................................................ 6 CHAPTER 1 Nicotine dependence ...................................................................................... 6 1.1 Biological mechanisms ............................................................................................................ 6 1.2 Nicotinic acetylcholine receptors ............................................................................................ 8 1.2.1 Protein structure ............................................................................................................. 8 1.2.2 Localization and function of neuronal nAChRs ............................................................. 10 1.2.3 α7 nAChRs ..................................................................................................................... 12 1.3 The genetics of nicotine dependence .................................................................................. -
Bestrophin 1 Is Indispensable for Volume Regulation in Human Retinal
Bestrophin 1 is indispensable for volume regulation in PNAS PLUS human retinal pigment epithelium cells Andrea Milenkovica, Caroline Brandla,b, Vladimir M. Milenkovicc, Thomas Jendrykec, Lalida Sirianantd, Potchanart Wanitchakoold, Stephanie Zimmermanna, Charlotte M. Reiffe, Franziska Horlinga, Heinrich Schrewef, Rainer Schreiberd, Karl Kunzelmannd, Christian H. Wetzelc, and Bernhard H. F. Webera,1 aInstitute of Human Genetics, cDepartment of Psychiatry and Psychotherapy, Molecular Neurosciences, and dDepartment of Physiology, University of Regensburg, 93053 Regensburg, Germany; bUniversity Eye Clinic, 93053 Regensburg, Germany; eEye Center, Albert-Ludwigs-University of Freiburg, 79106 Freiburg, Germany; and fDepartment of Developmental Genetics, Max Planck Institute for Molecular Genetics, 14195 Berlin, Germany Edited by Jeremy Nathans, Johns Hopkins University, Baltimore, MD, and approved March 16, 2015 (received for review October 1, 2014) In response to cell swelling, volume-regulated anion channels (VRACs) (12). The abnormalities in the LP were suggested to be com- + − participate in a process known as regulatory volume decrease (RVD). patible with a function of BEST1 as a Ca2 -activated Cl channel Only recently, first insight into the molecular identity of mammalian (CaCC) (13, 14). VRACs was obtained by the discovery of the leucine-rich repeats Addressing BEST1 function, several studies have suggested a + containing 8A (LRRC8A) gene. Here, we show that bestrophin 1 role of the protein in distinct basic cellular processes such as Ca2 (BEST1) but not LRRC8A is crucial for volume regulation in human homeostasis, neurotransmitter release, and cell volume regulation. retinal pigment epithelium (RPE) cells. Whole-cell patch-clamp These studies mostly relied on BEST1 overexpression in HEK293 recordings in RPE derived from human-induced pluripotent stem cells or conducted in vitro experiments with isolated cells from cells (hiPSC) exhibit an outwardly rectifying chloride current with existing Best1-deficient mouse lines. -
The Role of Catsper1 and Catsper2 Ion Channels in Male Fertility and Infertility
Available online at www.sciencedirect.com ScienceDirect Procedia Materials Science 10 ( 2015 ) 730 – 736 2nd International Conference on Nanomaterials and Technologies (CNT 2014) The role of CatSper1 and CatSper2 ion channels in male fertility and infertility Saikat Sahaa,b, Keka Talukdara, Amit K. Chakrabortya,b* a.Carbon Nanotechnology Group, Department of Physics, National Institute of Technology Durgapur-713209, West Bengal, India bCentre of Excellence in Advanced Materials, National Institute of Technology Durgapur-713209, West Bengal, India Abstract Ion channels in human body play multiple roles in many important biological processes. They regulate sperm maturation in the female reproductive tract and facilitates in hyperactivated motility, maturity through capacitation and acrosome reaction. The four sperm-associated cation channel, known as CatSpers and different ligand gated and voltage gated ion channels have been found to play crucial role for sperm physiology preparation for fertilization. The major function for maintaining Ca2+ concentration in flagellum is governed by CatSper channels in plasma membrane. Until now the role of these channels are not very clear. Here we have analysed the PDB structure (generated so far) of CatSper1 and CatSper2 channel proteins and found their ligand binding sites. The calculations are done by Charmm potential. Energies are calculated before and after ligand binding. We have also carried out Molecular Dynamics (MD) simulation for the protein model after filling up the simulation box with water and a number of K+ and Cl- ions. We see that the opening and closing of the channel pores depend on the binding of ligands. ©© 20152015 The The Authors. Authors. Published Published by Elsevierby Elsevier Ltd. -
Multidose Evaluation of 6,710 Drug Repurposing Library Identifies Potent SARS-Cov-2 Infection Inhibitors in Vitro and in Vivo
bioRxiv preprint doi: https://doi.org/10.1101/2021.04.20.440626; this version posted April 22, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Multidose evaluation of 6,710 drug repurposing library identifies potent SARS-CoV-2 infection inhibitors In Vitro and In Vivo. JJ Patten1, P. T. Keiser 1, D. Gysi2,3, G. Menichetti 2,3, H. Mori 1, C. J. Donahue 1, X. Gan 2,3, I. Do Valle 2, , K. Geoghegan-Barek 1, M. Anantpadma 1,4, J. L. Berrigan 1, S. Jalloh1, T. Ayazika1, F. Wagner6, M. Zitnik 2, S. Ayehunie6, D. Anderson1, J. Loscalzo3, S. Gummuluru1, M. N. Namchuk7, A. L. Barabasi2,3,8, and R. A. Davey1. Addresses: 1. Department of Microbiology, Boston University School of Medicine and NEIDL, Boston University, Boston, MA, 02118, USA. 2. Center for Complex Network Research, Northeastern University, Boston, Massachusetts 02115, USA. 3. Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA. 4. present address: Analytical Development, WuXi Advanced Therapies, Philadelphia, PA, 19112, USA. 5. Center for the Development of Therapeutics, Broad Institute of Harvard and MIT, Cambridge, MA, 02142, USA. 6. MatTek Corporation, Ashland, MA 01721, USA. 7. Department of Biological Chemistry and Molecular Pharmacology, Blavatnik Institute, Harvard Medical School, Boston, MA. 02115, USA. 8. Department of Network and Data Science, Central European University, Budapest 1051, Hungary. Abstract The SARS-CoV-2 pandemic has caused widespread illness, loss of life, and socioeconomic disruption that is unlikely to resolve until vaccines are widely adopted, and effective therapeutic treatments become established. -
Novel Targets of Apparently Idiopathic Male Infertility
International Journal of Molecular Sciences Review Molecular Biology of Spermatogenesis: Novel Targets of Apparently Idiopathic Male Infertility Rossella Cannarella * , Rosita A. Condorelli , Laura M. Mongioì, Sandro La Vignera * and Aldo E. Calogero Department of Clinical and Experimental Medicine, University of Catania, 95123 Catania, Italy; [email protected] (R.A.C.); [email protected] (L.M.M.); [email protected] (A.E.C.) * Correspondence: [email protected] (R.C.); [email protected] (S.L.V.) Received: 8 February 2020; Accepted: 2 March 2020; Published: 3 March 2020 Abstract: Male infertility affects half of infertile couples and, currently, a relevant percentage of cases of male infertility is considered as idiopathic. Although the male contribution to human fertilization has traditionally been restricted to sperm DNA, current evidence suggest that a relevant number of sperm transcripts and proteins are involved in acrosome reactions, sperm-oocyte fusion and, once released into the oocyte, embryo growth and development. The aim of this review is to provide updated and comprehensive insight into the molecular biology of spermatogenesis, including evidence on spermatogenetic failure and underlining the role of the sperm-carried molecular factors involved in oocyte fertilization and embryo growth. This represents the first step in the identification of new possible diagnostic and, possibly, therapeutic markers in the field of apparently idiopathic male infertility. Keywords: spermatogenetic failure; embryo growth; male infertility; spermatogenesis; recurrent pregnancy loss; sperm proteome; DNA fragmentation; sperm transcriptome 1. Introduction Infertility is a widespread condition in industrialized countries, affecting up to 15% of couples of childbearing age [1]. It is defined as the inability to achieve conception after 1–2 years of unprotected sexual intercourse [2].