DOCSLIB.ORG

Regulation of TRPM2 Channels by Fyn Kinase

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Regulation of TRPM2 Channels by Fyn Kinase Western University Scholarship@Western Electronic Thesis and Dissertation Repository 6-17-2013 12:00 AM Regulation of TRPM2 channels by Fyn kinase Matthew L. Johnston The University of Western Ontario Supervisor Dr. John F. MacDonald The University of Western Ontario Graduate Program in Physiology A thesis submitted in partial fulfillment of the equirr ements for the degree in Master of Science © Matthew L. Johnston 2013 Follow this and additional works at: https://ir.lib.uwo.ca/etd Part of the Cellular and Molecular Physiology Commons Recommended Citation Johnston, Matthew L., "Regulation of TRPM2 channels by Fyn kinase" (2013). Electronic Thesis and Dissertation Repository. 1308. https://ir.lib.uwo.ca/etd/1308 This Dissertation/Thesis is brought to you for free and open access by Scholarship@Western. It has been accepted for inclusion in Electronic Thesis and Dissertation Repository by an authorized administrator of Scholarship@Western. For more information, please contact [email protected]. REGULATION OF TRPM2 CHANNELS BY FYN KINASE (Thesis format: Monograph) by Matthew Lawrence Johnston Graduate Program in Physiology A thesis submitted in partial fulfillment of the requirements for the degree of Master of Science The School of Graduate and Postdoctoral Studies The University of Western Ontario London, Ontario, Canada © Matthew L. Johnston 2013 i Abstract TRPM2 is a calcium-permeable non-selective cation channel that acts as a mediator of cell death in response to oxidative stress. It has been shown that oxidative stress increases TRPM2 tyrosine phosphorylation and activation – an effect that is blocked by PP2, a non-specific inhibitor of Src family kinases. However, the kinase and target TRPM2 tyrosine residue(s) involved have not yet been identified. Here, we investigated the potential regulation of TRPM2 by Fyn. Intracellular application of recombinant Fyn potentiated TRPM2 currents in HEK293 cells expressing inducible TRPM2 (TRPM2- HEK293 cells). Further, a physical interaction between Fyn and TRPM2 was demonstrated by co-immunoprecipitation in TRPM2-HEK293 cells. Additionally, tyrosine phosphorylation of TRPM2 was induced by Fyn in TRPM2-HEK293 cells, and the amount of phosphorylation detected was related to the activation state of Fyn. We propose that by augmenting TRPM2 activity, Fyn kinase potentiates cellular calcium overload and facilitates cell death in response to oxidative stress. Keywords TRPM2, Fyn kinase, tyrosine phosphorylation, protein-protein interaction, calcium ii Co-Authorship Statement Drs. John MacDonald and Michael Jackson supervised and contributed to the design of all experiments discussed in this work. Dr. Jillian Belrose contributed to the design of the biochemistry experiments conducted in this work. Further, Dr. Belrose conducted an experiment assessing the effect of Fyn on TRPM2 currents in cultured hippocampal neurons (Appendix A, Fig. S1). Dr. Fabiana Caetano conducted preliminary electrophysiology experiments assessing the effect of Fyn on TRPM2. These experiments contributed to the design of the electrophysiological experiments described in this work. Additionally, Dr. Hongbin Li performed an experiment assessing the effect of a Fyn-interfering peptide (Fyn(39-57)) on TRPM2 currents in cultured hippocampal neurons (Appendix A, Fig. S2). iii Acknowledgments Firstly, I would like to extend my gratitude to my supervisors, Dr. John MacDonald and Dr. Michael Jackson for providing me with the opportunity to learn and develop under your guidance. Your expertise, feedback and support have been invaluable to the completion of this project. I have greatly enjoyed the time I have spent in your lab. I would also like to thank the members of my graduate advisory committee: Dr. Vania Prado, Dr. Stephen Ferguson, Dr. Wei-Yang Lu and Dr. Timothy Regnault. Your expertise, feedback and advice were highly beneficial to this project. Additionally, the funding provided for this project by the Canadian Institute of Health Research (CIHR), the Ontario Graduate Scholarship (OGS) program and Schulich School of Medicine and Dentistry is gratefully acknowledged. Additionally, I would like to thank the members of the MacDonald/Jackson lab for their continued support. Particularly, I would like to thank Dr. Jillian Belrose for invaluable contributions to these experiments, as well as Dr. Fabiana Caetano for helping to lay the groundwork for this project. Additionally, my gratitude is owed to Natalie Lavine for the technical assistance and time she devoted to this project. Also, I would like to thank Dr. Hongbin Li, Dr. Gang Lei, Brian Lockhart, Oies Hussein, Dr. Catherine Trepanier and Dr. Kai Yang for their support, feedback and various other contributions to this work. Completion of this project would not have been possible without this support. Lastly, I would like to thank my family and friends for the support they have provided throughout my academic career. iv Table of Contents Abstract ............................................................................................................................... ii Co-Authorship Statement................................................................................................... iii Acknowledgments.............................................................................................................. iv Table of Contents ................................................................................................................ v List of Tables .................................................................................................................... vii List of Figures .................................................................................................................. viii List of Appendices ............................................................................................................. ix List of Abbreviations .......................................................................................................... x Section 1: Introduction ........................................................................................................ 1 1.1 General introduction ............................................................................................... 2 1.2 Transient receptor potential melastatin 2 (TRPM2) ............................................... 2 1.3 Structural and biophysical properties of TRPM2 ................................................... 5 1.4 Oxidative stress and TRPM2 activation ................................................................. 9 1.5 Physiological roles of TRPM2 .............................................................................. 11 1.6 TRPM2 channels in CNS disease ......................................................................... 12 1.7 TRPM2 regulation mechanisms ............................................................................ 14 1.8 TRPM2 regulation by tyrosine phosphorylation................................................... 15 1.9 Fyn kinase ............................................................................................................. 16 1.10 TRPM2, Fyn and NMDA receptor signaling ...................................................... 19 1.11 Rationale and hypothesis ..................................................................................... 20 Section 2: Materials and Methods..................................................................................... 22 2.1 Cell culture ............................................................................................................ 23 2.2 Whole-cell voltage-clamp electrophysiology ....................................................... 23 2.3 Generation of TRPM2 constructs ......................................................................... 24 2.4 Transfection .......................................................................................................... 28 2.5 Immunoprecipitation and Western blotting .......................................................... 29 2.6 Drugs and peptides ................................................................................................ 29 2.7 Data analysis and statistics.................................................................................... 30 Section 3: Results .............................................................................................................. 31 3.1 Regulation of TRPM2 currents by Fyn kinase ..................................................... 32 3.2 Expression of Fyn and TRPM2 in TRPM2-HEK293 cells ................................... 34 3.3 Tyrosine phosphorylation of TRPM2 induced by Fyn kinase .............................. 36 3.4 Physical interaction between Fyn kinase and TRPM2 ......................................... 39 3.5 Expression of Fyn and TRPM2 in HEK293T cells .............................................. 40 3.6 Tyrosine phosphorylation of wild-type and mutant TRPM2 by Fyn kinase ........ 44 3.7 Physical interaction between Fyn kinase and wild-type or mutant TRPM2 ......... 45 v Section 4: Discussion ........................................................................................................ 50 4.1 Summary of key findings ...................................................................................... 51 4.2 Regulation of TRPM2 by Fyn kinase ................................................................... 51 4.3 Identification of TRPM2 tyrosine residue(s) responsible for Fyn modulation ..... 53
Load more

Recommended publications
  • The Direct and Functional Interaction of Tubulin with Transient Receptor Potential Melastatin 2
    The Direct and Functional Interaction of Tubulin With Transient Receptor Potential Melastatin 2 by Colin Elliott Seepersad A thesis submitted in conformity with the requirements for the degree of Masters of Science Cell & Systems Biology University of Toronto © Copyright by Colin Elliott Seepersad 2011 The Direct and Functional Interaction of Tubulin With Transient Receptor Potential Melastatin 2 Colin Elliott Seepersad Masters of Science Cell & Systems Biology University of Toronto 2011 Abstract Transient Receptor Potential Melastatin 2 (TRPM2) is a widely expressed, non-selective cationic channel with implicated roles in cell death, chemokine production and oxidative stress. This study characterizes a novel interactor of TRPM2. Using fusion proteins comprised of the TRPM2 C-terminus we established that tubulin interacted directly with the predicted C-terminal coiled-coil domain of the channel. In vitro studies revealed increased interaction between tubulin and TRPM2 during LPS-induced macrophage activation and taxol-induced microtubule stabilization. We propose that the stabilization of microtubules in activated macrophages enhances the interaction of tubulin with TRPM2 resulting in the gating and/or localization of the channel resulting in a contribution to increased intracellular calcium and downstream production of chemokines. ii Acknowledgments I would like to thank my supervisor Dr. Michelle Aarts for providing me with the opportunity to pursuit a Master’s of Science Degree at the University of Toronto. Since my days as an undergraduate thesis student, Michelle has provided me with the knowledge, tools and environment to succeed. I am very grateful for the experience and will move forward a more rounded and mature student. Special thanks to my committee members, Dr.
    [Show full text]
  • TRPM2 in the Brain: Role in Health and Disease
    cells Review TRPM2 in the Brain: Role in Health and Disease Giulia Sita ID , Patrizia Hrelia * ID , Agnese Graziosi ID , Gloria Ravegnini and Fabiana Morroni ID Department of Pharmacy and Biotechnology, Alma Mater Studiorum, University of Bologna, Via Irnerio 48, 40126 Bologna, Italy; [email protected] (G.S.); [email protected] (A.G.); [email protected] (G.R.); [email protected] (F.M.) * Correspondence: [email protected]; Tel.: +39-051-209-1799 Received: 8 June 2018; Accepted: 20 July 2018; Published: 22 July 2018 Abstract: Transient receptor potential (TRP) proteins have been implicated in several cell functions as non-selective cation channels, with about 30 different mammalian TRP channels having been recognized. Among them, TRP-melastatin 2 (TRPM2) is particularly involved in the response to oxidative stress and inflammation, while its activity depends on the presence of intracellular calcium (Ca2+). TRPM2 is involved in several physiological and pathological processes in the brain through the modulation of multiple signaling pathways. The aim of the present review is to provide a brief summary of the current insights of TRPM2 role in health and disease to focalize our attention on future potential neuroprotective strategies. Keywords: TRPM2; brain; aging; neurodegeneration; neurodegenerative disease 1. Introduction Transient receptor potential (TRP) proteins form non-selective cation channels which are involved in several cell functions in activated form. To date, about 30 different mammalian TRP channels have been recognized, which are divided into six subfamilies: TRPA (Ankyrin), TRPC (canonical), TRPM (melastatin), TRPML (mucolipin), TRPP (polycystin) and TRPV (vanilloid) [1]. Most TRP channels have a role in sensory perception in animals and they all share structural similarities [2].
    [Show full text]
  • Therapeutic Potential of TRPM Modulator
    Online Journal of Neurology and Brain Disorders DOI: 10.32474/OJNBD.2020.04.000192 ISSN: 2637-6628 Review Article Therapeutic Potential of TRPM Modulator Nitin Rawat, Hemprabha Tainguriya and Anil Kumar* Pharmacology Department, University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Studies (UGC-CAS), Panjab University, India *Corresponding author: Anil Kumar, Professor of Pharmacology, Former Dean, Faculty of Pharmaceutical Sciences, University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Studies (UGC-CAS), Panjab University, Chandigarh, India Received: September 24, 2020 Published: October 06, 2020 Abstract Transient Receptor Potential of the family Melastatin (TRPM) is a group of nonselective cation channel, engaged in various daily skin. Soon after TRPM1 was discovered, another family member was discovered, that includes TRPM2 (channel sensitive to oxidative stressactivities present of the in body. microglial The family’s cells), TRPM3first member (channel (TRPM1) activating was renalcloned homeostasis in 1998 capable that is of activated supressing by thesphingosine), tumour in TRPM4/5melanocytes (Ca of+2 activated sister channel involved in conduction of monovalent cation), TRPM6/7 (chanzymes related to Mg+2 homeostasis), TRPM8 (thermosensitive Ca+2 permeable channel). This review will summarize activation of key structural features mechanism and therapeutic potential of drug modulating TRPM channels. Keywords: Transient Receptor Potential (TRP) Channels; TRPM Modulators; Neurodegenerative Diseases;
    [Show full text]
  • Ion Channels in the Pathogenesis of Endometriosis: a Cutting-Edge Point of View
    International Journal of Molecular Sciences Review Ion Channels in The Pathogenesis of Endometriosis: A Cutting-Edge Point of View 1, 2, 1, Gaetano Riemma y , Antonio Simone Laganà y , Antonio Schiattarella * , Simone Garzon 2 , Luigi Cobellis 1, Raffaele Autiero 1, Federico Licciardi 1, Luigi Della Corte 3 , Marco La Verde 1 and Pasquale De Franciscis 1 1 Department of Woman, Child and General and Specialized Surgery, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy; [email protected] (G.R.); [email protected] (L.C.); raff[email protected] (R.A.); [email protected] (F.L.); [email protected] (M.L.V.); [email protected] (P.D.F.) 2 Department of Obstetrics and Gynecology, “Filippo Del Ponte” Hospital, University of Insubria, 21100 Varese, Italy; [email protected] (A.S.L.); [email protected] (S.G.) 3 Department of Neuroscience, Reproductive Sciences and Dentistry, School of Medicine, University of Naples Federico II, 80131 Naples, Italy; [email protected] * Correspondence: [email protected]; Tel.: +39-392-165-3275 Equal contributions (joint first authors). y Received: 30 December 2019; Accepted: 5 February 2020; Published: 7 February 2020 Abstract: Background: Ion channels play a crucial role in many physiological processes. Several subtypes are expressed in the endometrium. Endometriosis is strictly correlated to estrogens and it is evident that expression and functionality of different ion channels are estrogen-dependent, fluctuating between the menstrual phases. However, their relationship with endometriosis is still unclear. Objective: To summarize the available literature data about the role of ion channels in the etiopathogenesis of endometriosis.
    [Show full text]
  • Properties and Therapeutic Potential of Transient Receptor Potential Channels with Putative Roles in Adversity: Focus on TRPC5, TRPM2 and TRPA1
    724 Current Drug Targets, 2011, 12, 724-736 Properties and Therapeutic Potential of Transient Receptor Potential Channels with Putative Roles in Adversity: Focus on TRPC5, TRPM2 and TRPA1 L.H. Jiang, N. Gamper and D.J. Beech* Institute of Membrane and Systems Biology, Faculty of Biological Sciences, University of Leeds, Leeds, LS2 9JT, UK Abstract: Mammals contain 28 genes encoding Transient Receptor Potential (TRP) proteins. The proteins assemble into cationic channels, often with calcium permeability. Important roles in physiology and disease have emerged and so there is interest in whether the channels might be suitable therapeutic drug targets. Here we review selected members of three subfamilies of mammalian TRP channel (TRPC5, TRPM2 and TRPA1) that show relevance to sensing of adversity by cells and biological systems. Summarized are the cellular and tissue distributions, general properties, endogenous modulators, protein partners, cellular and tissue functions, therapeutic potential, and pharmacology. TRPC5 is stimulated by receptor agonists and other factors that include lipids and metal ions; it heteromultimerises with other TRPC proteins and is involved in cell movement and anxiety control. TRPM2 is activated by hydrogen peroxide; it is implicated in stress-related inflammatory, vascular and neurodegenerative conditions. TRPA1 is stimulated by a wide range of irritants including mustard oil and nicotine but also, controversially, noxious cold and mechanical pressure; it is implicated in pain and inflammatory responses, including in the airways. The channels have in common that they show polymodal stimulation, have activities that are enhanced by redox factors, are permeable to calcium, and are facilitated by elevations of intracellular calcium. Developing inhibitors of the channels could lead to new agents for a variety of conditions: for example, suppressing unwanted tissue remodeling, inflammation, pain and anxiety, and addressing problems relating to asthma and stroke.
    [Show full text]
  • Free PDF Download
    European Review for Medical and Pharmacological Sciences 2019; 23: 3088-3095 The effects of TRPM2, TRPM6, TRPM7 and TRPM8 gene expression in hepatic ischemia reperfusion injury T. BILECIK1, F. KARATEKE2, H. ELKAN3, H. GOKCE4 1Department of Surgery, Istinye University, Faculty of Medicine, VM Mersin Medical Park Hospital, Mersin, Turkey 2Department of Surgery, VM Mersin Medical Park Hospital, Mersin, Turkey 3Department of Surgery, Sanlıurfa Training and Research Hospital, Sanliurfa, Turkey 4Department of Pathology, Inonu University, Faculty of Medicine, Malatya, Turkey Abstract. – OBJECTIVE: Mammalian transient Introduction receptor potential melastatin (TRPM) channels are a form of calcium channels and they trans- Ischemia is the lack of oxygen and nutrients port calcium and magnesium ions. TRPM has and the cause of mechanical obstruction in sev- eight subclasses including TRPM1-8. TRPM2, 1 TRPM6, TRPM7, TRPM8 are expressed especial- eral tissues . Hepatic ischemia and reperfusion is ly in the liver cell. Therefore, we aim to investi- a serious complication and cause of cell death in gate the effects of TRPM2, TRPM6, TRPM7, and liver tissue2. The resulting ischemic liver tissue TRPM8 gene expression and histopathologic injury increases free intracellular calcium. Intra- changes after treatment of verapamil in the he- cellular calcium has been defined as an important patic ischemia-reperfusion rat model. secondary molecular messenger ion, suggesting MATERIALS AND METHODS: Animals were randomly assigned to one or the other of the calcium’s effective role in cell injury during isch- following groups including sham (n=8) group, emia-reperfusion, when elevated from normal verapamil (calcium entry blocker) (n=8) group, concentrations. The high calcium concentration I/R group (n=8) and I/R- verapamil (n=8) group.
    [Show full text]
  • The Role of TRP Channels in Pain and Taste Perception
    International Journal of Molecular Sciences Review Taste the Pain: The Role of TRP Channels in Pain and Taste Perception Edwin N. Aroke 1 , Keesha L. Powell-Roach 2 , Rosario B. Jaime-Lara 3 , Markos Tesfaye 3, Abhrarup Roy 3, Pamela Jackson 1 and Paule V. Joseph 3,* 1 School of Nursing, University of Alabama at Birmingham, Birmingham, AL 35294, USA; [email protected] (E.N.A.); [email protected] (P.J.) 2 College of Nursing, University of Florida, Gainesville, FL 32611, USA; keesharoach@ufl.edu 3 Sensory Science and Metabolism Unit (SenSMet), National Institute of Nursing Research, National Institutes of Health, Bethesda, MD 20892, USA; [email protected] (R.B.J.-L.); [email protected] (M.T.); [email protected] (A.R.) * Correspondence: [email protected]; Tel.: +1-301-827-5234 Received: 27 July 2020; Accepted: 16 August 2020; Published: 18 August 2020 Abstract: Transient receptor potential (TRP) channels are a superfamily of cation transmembrane proteins that are expressed in many tissues and respond to many sensory stimuli. TRP channels play a role in sensory signaling for taste, thermosensation, mechanosensation, and nociception. Activation of TRP channels (e.g., TRPM5) in taste receptors by food/chemicals (e.g., capsaicin) is essential in the acquisition of nutrients, which fuel metabolism, growth, and development. Pain signals from these nociceptors are essential for harm avoidance. Dysfunctional TRP channels have been associated with neuropathic pain, inflammation, and reduced ability to detect taste stimuli. Humans have long recognized the relationship between taste and pain. However, the mechanisms and relationship among these taste–pain sensorial experiences are not fully understood.
    [Show full text]
  • Transient Receptor Potential Channels As Drug Targets: from the Science of Basic Research to the Art of Medicine
    1521-0081/66/3/676–814$25.00 http://dx.doi.org/10.1124/pr.113.008268 PHARMACOLOGICAL REVIEWS Pharmacol Rev 66:676–814, July 2014 Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics ASSOCIATE EDITOR: DAVID R. SIBLEY Transient Receptor Potential Channels as Drug Targets: From the Science of Basic Research to the Art of Medicine Bernd Nilius and Arpad Szallasi KU Leuven, Department of Cellular and Molecular Medicine, Laboratory of Ion Channel Research, Campus Gasthuisberg, Leuven, Belgium (B.N.); and Department of Pathology, Monmouth Medical Center, Long Branch, New Jersey (A.S.) Abstract. ....................................................................................679 I. Transient Receptor Potential Channels: A Brief Introduction . ...............................679 A. Canonical Transient Receptor Potential Subfamily . .....................................682 B. Vanilloid Transient Receptor Potential Subfamily . .....................................686 C. Melastatin Transient Receptor Potential Subfamily . .....................................696 Downloaded from D. Ankyrin Transient Receptor Potential Subfamily .........................................700 E. Mucolipin Transient Receptor Potential Subfamily . .....................................702 F. Polycystic Transient Receptor Potential Subfamily . .....................................703 II. Transient Receptor Potential Channels: Hereditary Diseases (Transient Receptor Potential Channelopathies). ......................................................704
    [Show full text]
  • Characterization and Optimization of the Novel TRPM2 Antagonist Tatm2nx
    Molecular Pharmacology Fast Forward. Published on November 26, 2019 as DOI: 10.1124/mol.119.117549 This article has not been copyedited and formatted. The final version may differ from this version. MOL Manuscript # 117549 Characterization and optimization of the novel TRPM2 antagonist tatM2NX Cruz-Torres, I.; Backos, D.S.; and Herson, P.S. Department of Pharmacology, University of Colorado School of Medicine, Aurora, CO, USA (I.C.T, P.S.H.) Department of Pharmaceutical Sciences, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO, USA (D.S.B.) Downloaded from Department of Anesthesiology, University of Colorado School of Medicine, Aurora, CO, USA (P.S.H.) molpharm.aspetjournals.org Neuronal Injury & Plasticity Program, University of Colorado School of Medicine, Aurora, CO, USA (I.C.T, P.S.H.) Corresponding author: Ivelisse Cruz-Torres ([email protected]), Paco S. at ASPET Journals on September 29, 2021 Herson ([email protected]); telephone: 303-724-6628; fax: 303-724-1761 Address: Department of Pharmacology, University of Colorado School of Medicine, Aurora, CO, USA 1 Molecular Pharmacology Fast Forward. Published on November 26, 2019 as DOI: 10.1124/mol.119.117549 This article has not been copyedited and formatted. The final version may differ from this version. MOL Manuscript # 117549 Running title: Characterization of the TRPM2 antagonist tatM2NX Number of text pages: 32 Number of tables: 2 Number of figures: 4 Number of references: 75 Downloaded from Number of words abstract:
    [Show full text]
  • Characterization of Membrane Proteins: from a Gated Plant Aquaporin to Animal Ion Channel Receptors
    Characterization of Membrane Proteins: From a gated plant aquaporin to animal ion channel receptors Survery, Sabeen 2015 Link to publication Citation for published version (APA): Survery, S. (2015). Characterization of Membrane Proteins: From a gated plant aquaporin to animal ion channel receptors. Department of Biochemistry and Structural Biology, Lund University. Total number of authors: 1 General rights Unless other specific re-use rights are stated the following general rights apply: Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights. • Users may download and print one copy of any publication from the public portal for the purpose of private study or research. • You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal Read more about Creative commons licenses: https://creativecommons.org/licenses/ Take down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. LUND UNIVERSITY PO Box 117 221 00 Lund +46 46-222 00 00 Printed by Media-Tryck, Lund University 2015 SURVERY SABEEN Characterization of Membrane Proteins - From a gated plant aquaporin to animal ion channel
    [Show full text]
  • The Role of the Aquaporin 5 in the Function of Late Pregnant Rat Uterus: Pharmacological Studies
    University of Szeged Faculty of Pharmacy Department of Pharmacodynamics and Biopharmacy The role of the aquaporin 5 in the function of late pregnant rat uterus: pharmacological studies Ph.D. Thesis Adrienn Csányi Supervisor: Eszter Ducza Ph.D. 2019 Contents Contents ...................................................................................................................................... 1 List of publications ..................................................................................................................... 3 List of abbreviations ................................................................................................................... 5 1 Introduction ........................................................................................................................ 6 1.1 The role of the AQP water channels in the female reproductive system .................... 7 1.2 AQP5 in the pregnant rat uterus ................................................................................ 10 1.3 The effects of sexual hormones on the AQP5 expression ......................................... 11 1.4 Preterm birth, antibiotic treatment and AQP ............................................................. 12 1.5 Transient receptor potential vanilloid 4 and AQP5 channel ...................................... 13 2 Aims ................................................................................................................................. 16 3 Materials and methods ....................................................................................................
    [Show full text]
  • The Role of TRPM2 Channels in Oxidative Stress-Induced Liver Damage
    The role of TRPM2 channels in oxidative stress-induced liver damage Ehsan Kheradpezhouh Discipline of Physiology, School of Medical Sciences University of Adelaide Submitted for the degree of Doctor of Philosophy December 2014 Contents List of Abbreviations ....................................................................................................... i Abstract ........................................................................................................................... v Declaration of Originality ............................................................................................vii Acknowledgements ......................................................................................................... x Chapter 1: Research Background ................................................................................. 1 1.1 Introduction ............................................................................................................ 1 1.2 Oxidative Stress ...................................................................................................... 4 1.2.1 Systems Eliminating Oxidative Compounds ................................................... 5 1.2.2 Cellular and Molecular Targets of Oxidative Stress ....................................... 6 1.2.3 Mechanisms of Oxidative Stress Mediated Cellular Damage ......................... 8 2+ 1.3 Oxidative Damage and Ca Signalling................................................................ 11 1.4 TRP Channels in Oxidative Stress ......................................................................
    [Show full text]