Information Topology of Gene Expression Profile in Dopaminergic Neurons
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TRP Channels in Digestive Tract Cancers
International Journal of Molecular Sciences Review TRP Channels in Digestive Tract Cancers Paulina Stokłosa *, Anna Borgström, Sven Kappel and Christine Peinelt Institute of Biochemistry and Molecular Medicine, National Center of Competence in Research NCCR TransCure, University of Bern, 3012 Bern, Switzerland; [email protected] (A.B.); [email protected] (S.K.); [email protected] (C.P.) * Correspondence: [email protected]; Tel.: +0041-(0)31-631-34-26 Received: 10 February 2020; Accepted: 6 March 2020; Published: 9 March 2020 Abstract: Cancers of the digestive tract are among the most prevalent types of cancer. These types of cancers are often diagnosed at a late stage, which results in a poor prognosis. Currently, many biomedical studies focus on the role of ion channels, in particular transient receptor potential (TRP) channels, in cancer pathophysiology. TRP channels show mostly non-selective permeability to monovalent and divalent cations. TRP channels are often dysregulated in digestive tract cancers, which can result in alterations of cancer hallmark functions, such as enhanced proliferation, migration, invasion and the inability to induce apoptosis. Therefore, TRP channels could serve as potential diagnostic biomarkers. Moreover, TRP channels are mostly expressed on the cell surface and ion channel targeting drugs do not need to enter the cell, making them attractive candidate drug targets. In this review, we summarize the current knowledge about TRP channels in connection to digestive tract cancers (oral cancer, esophageal cancer, liver cancer, pancreatic cancer, gastric cancer and colorectal cancer) and give an outlook on the potential of TRP channels as cancer biomarkers or therapeutic targets. -
The Mineralocorticoid Receptor Leads to Increased Expression of EGFR
www.nature.com/scientificreports OPEN The mineralocorticoid receptor leads to increased expression of EGFR and T‑type calcium channels that support HL‑1 cell hypertrophy Katharina Stroedecke1,2, Sandra Meinel1,2, Fritz Markwardt1, Udo Kloeckner1, Nicole Straetz1, Katja Quarch1, Barbara Schreier1, Michael Kopf1, Michael Gekle1 & Claudia Grossmann1* The EGF receptor (EGFR) has been extensively studied in tumor biology and recently a role in cardiovascular pathophysiology was suggested. The mineralocorticoid receptor (MR) is an important efector of the renin–angiotensin–aldosterone‑system and elicits pathophysiological efects in the cardiovascular system; however, the underlying molecular mechanisms are unclear. Our aim was to investigate the importance of EGFR for MR‑mediated cardiovascular pathophysiology because MR is known to induce EGFR expression. We identifed a SNP within the EGFR promoter that modulates MR‑induced EGFR expression. In RNA‑sequencing and qPCR experiments in heart tissue of EGFR KO and WT mice, changes in EGFR abundance led to diferential expression of cardiac ion channels, especially of the T‑type calcium channel CACNA1H. Accordingly, CACNA1H expression was increased in WT mice after in vivo MR activation by aldosterone but not in respective EGFR KO mice. Aldosterone‑ and EGF‑responsiveness of CACNA1H expression was confrmed in HL‑1 cells by Western blot and by measuring peak current density of T‑type calcium channels. Aldosterone‑induced CACNA1H protein expression could be abrogated by the EGFR inhibitor AG1478. Furthermore, inhibition of T‑type calcium channels with mibefradil or ML218 reduced diameter, volume and BNP levels in HL‑1 cells. In conclusion the MR regulates EGFR and CACNA1H expression, which has an efect on HL‑1 cell diameter, and the extent of this regulation seems to depend on the SNP‑216 (G/T) genotype. -
Towards Mutation-Specific Precision Medicine in Atypical Clinical
International Journal of Molecular Sciences Review Towards Mutation-Specific Precision Medicine in Atypical Clinical Phenotypes of Inherited Arrhythmia Syndromes Tadashi Nakajima * , Shuntaro Tamura, Masahiko Kurabayashi and Yoshiaki Kaneko Department of Cardiovascular Medicine, Gunma University Graduate School of Medicine, Maebashi 371-8511, Gunma, Japan; [email protected] (S.T.); [email protected] (M.K.); [email protected] (Y.K.) * Correspondence: [email protected]; Tel.: +81-27-220-8145; Fax: +81-27-220-8158 Abstract: Most causal genes for inherited arrhythmia syndromes (IASs) encode cardiac ion channel- related proteins. Genotype-phenotype studies and functional analyses of mutant genes, using heterol- ogous expression systems and animal models, have revealed the pathophysiology of IASs and enabled, in part, the establishment of causal gene-specific precision medicine. Additionally, the utilization of induced pluripotent stem cell (iPSC) technology have provided further insights into the patho- physiology of IASs and novel promising therapeutic strategies, especially in long QT syndrome. It is now known that there are atypical clinical phenotypes of IASs associated with specific mutations that have unique electrophysiological properties, which raises a possibility of mutation-specific precision medicine. In particular, patients with Brugada syndrome harboring an SCN5A R1632C mutation exhibit exercise-induced cardiac events, which may be caused by a marked activity-dependent loss of R1632C-Nav1.5 availability due to a marked delay of recovery from inactivation. This suggests that the use of isoproterenol should be avoided. Conversely, the efficacy of β-blocker needs to be examined. Patients harboring a KCND3 V392I mutation exhibit both cardiac (early repolarization syndrome and Citation: Nakajima, T.; Tamura, S.; paroxysmal atrial fibrillation) and cerebral (epilepsy) phenotypes, which may be associated with a Kurabayashi, M.; Kaneko, Y. -
The Role of TRP Channels in the Metastatic Cascade
pharmaceuticals Review The Role of TRP Channels in the Metastatic Cascade Benedikt Fels *, Etmar Bulk, Zoltán Peth˝oand Albrecht Schwab Institut für Physiologie II, Robert-Koch-Str. 27b, 48149 Münster, Germany; [email protected] (E.B.); [email protected] (Z.P.); [email protected] (A.S.) * Correspondence: [email protected]; Tel.: +49-251-83-55336 Received: 20 April 2018; Accepted: 16 May 2018; Published: 17 May 2018 Abstract: A dysregulated cellular Ca2+ homeostasis is involved in multiple pathologies including cancer. Changes in Ca2+ signaling caused by altered fluxes through ion channels and transporters (the transportome) are involved in all steps of the metastatic cascade. Cancer cells thereby “re-program” and “misuse” the cellular transportome to regulate proliferation, apoptosis, metabolism, growth factor signaling, migration and invasion. Cancer cells use their transportome to cope with diverse environmental challenges during the metastatic cascade, like hypoxic, acidic and mechanical cues. Hence, ion channels and transporters are key modulators of cancer progression. This review focuses on the role of transient receptor potential (TRP) channels in the metastatic cascade. After briefly introducing the role of the transportome in cancer, we discuss TRP channel functions in cancer cell migration. We highlight the role of TRP channels in sensing and transmitting cues from the tumor microenvironment and discuss their role in cancer cell invasion. We identify open questions concerning the role of TRP channels in circulating tumor cells and in the processes of intra- and extravasation of tumor cells. We emphasize the importance of TRP channels in different steps of cancer metastasis and propose cancer-specific TRP channel blockade as a therapeutic option in cancer treatment. -
The Metabotropic Glutamate Receptor Mglur1 Regulates the Voltage-Gated Potassium Channel Kv1.2 Through Agonist-Dependent and Agonist-Independent Mechanisms
University of Vermont ScholarWorks @ UVM Graduate College Dissertations and Theses Dissertations and Theses 2019 The etM abotropic glutamate receptor mGluR1 regulates the voltage-gated potassium channel Kv1.2 through agonist-dependent and agonist- independent mechanisms Sharath Chandra Madasu University of Vermont Follow this and additional works at: https://scholarworks.uvm.edu/graddis Part of the Cell Biology Commons, Neuroscience and Neurobiology Commons, and the Pharmacology Commons Recommended Citation Madasu, Sharath Chandra, "The eM tabotropic glutamate receptor mGluR1 regulates the voltage-gated potassium channel Kv1.2 through agonist-dependent and agonist-independent mechanisms" (2019). Graduate College Dissertations and Theses. 982. https://scholarworks.uvm.edu/graddis/982 This Dissertation is brought to you for free and open access by the Dissertations and Theses at ScholarWorks @ UVM. It has been accepted for inclusion in Graduate College Dissertations and Theses by an authorized administrator of ScholarWorks @ UVM. For more information, please contact [email protected]. THE METABOTROPIC GLUTAMATE RECEPTOR MGLUR1 REGULATES THE VOLTAGE-GATED POTASSIUM CHANNEL KV1.2 THROUGH AGONIST-DEPENDENT AND AGONIST-INDEPENDENT MECHANISMS. A Dissertation Presented by Sharath Chandra Madasu to The Faculty of the Graduate College of The University of Vermont In Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy Specializing in Cellular Molecular and Biomedical Science January, 2019 Defense Date: September 27, 2018 Dissertation Examination Committee: Anthony D. Morielli, PhD., Advisor John Green, PhD., Chairperson Karen Lounsbury, Ph.D. Benedek Erdos, PhD. Cynthia J. Forehand, Ph.D., Dean of the Graduate College ABSTRACT The voltage gated potassium channel Kv1.2 plays a key role in the central nervous system and mutations in Kv1.2 cause neurological disorders such as epilepsies and ataxias. -
KCND3 Potassium Channel Gene Variant Confers Susceptibility to Electrocardiographic Early Repolarization Pattern
KCND3 potassium channel gene variant confers susceptibility to electrocardiographic early repolarization pattern Alexander Teumer, … , Elijah R. Behr, Wibke Reinhard JCI Insight. 2019. https://doi.org/10.1172/jci.insight.131156. Clinical Medicine In-Press Preview Cardiology Genetics Graphical abstract Find the latest version: https://jci.me/131156/pdf 1 KCND3 potassium channel gene variant confers susceptibility to 2 electrocardiographic early repolarization pattern 3 Alexander Teumer1,2*, Teresa Trenkwalder3*, Thorsten Kessler3, Yalda Jamshidi4, Marten E. van den 4 Berg5, Bernhard Kaess6, Christopher P. Nelson7,8, Rachel Bastiaenen9, Marzia De Bortoli10, 5 Alessandra Rossini10, Isabel Deisenhofer3, Klaus Stark11, Solmaz Assa12, Peter S. Braund7,8, Claudia 6 Cabrera13,14,15, Anna F. Dominiczak16, Martin Gögele10, Leanne M. Hall7,8, M. Arfan Ikram5, Maryam 7 Kavousi5, Karl J. Lackner17,18, Lifelines Cohort Study19, Christian Müller20, Thomas Münzel18,21, 8 Matthias Nauck2,22, Sandosh Padmanabhan16, Norbert Pfeiffer23, Tim D. Spector24, Andre G. 9 Uitterlinden5, Niek Verweij12, Uwe Völker2,25, Helen R. Warren13,14, Mobeen Zafar12, Stephan B. 10 Felix2,26, Jan A. Kors27, Harold Snieder28, Patricia B. Munroe13,14, Cristian Pattaro10, Christian 11 Fuchsberger10, Georg Schmidt29,30, Ilja M. Nolte28, Heribert Schunkert3,30, Peter Pramstaller10, Philipp 12 S. Wild31, Pim van der Harst12, Bruno H. Stricker5, Renate B. Schnabel20, Nilesh J. Samani7,8, 13 Christian Hengstenberg32, Marcus Dörr2,26, Elijah R. Behr33, Wibke Reinhard3 14 15 16 1 Institute -
Expression Profiling of Ion Channel Genes Predicts Clinical Outcome in Breast Cancer
UCSF UC San Francisco Previously Published Works Title Expression profiling of ion channel genes predicts clinical outcome in breast cancer Permalink https://escholarship.org/uc/item/1zq9j4nw Journal Molecular Cancer, 12(1) ISSN 1476-4598 Authors Ko, Jae-Hong Ko, Eun A Gu, Wanjun et al. Publication Date 2013-09-22 DOI http://dx.doi.org/10.1186/1476-4598-12-106 Peer reviewed eScholarship.org Powered by the California Digital Library University of California Ko et al. Molecular Cancer 2013, 12:106 http://www.molecular-cancer.com/content/12/1/106 RESEARCH Open Access Expression profiling of ion channel genes predicts clinical outcome in breast cancer Jae-Hong Ko1, Eun A Ko2, Wanjun Gu3, Inja Lim1, Hyoweon Bang1* and Tong Zhou4,5* Abstract Background: Ion channels play a critical role in a wide variety of biological processes, including the development of human cancer. However, the overall impact of ion channels on tumorigenicity in breast cancer remains controversial. Methods: We conduct microarray meta-analysis on 280 ion channel genes. We identify candidate ion channels that are implicated in breast cancer based on gene expression profiling. We test the relationship between the expression of ion channel genes and p53 mutation status, ER status, and histological tumor grade in the discovery cohort. A molecular signature consisting of ion channel genes (IC30) is identified by Spearman’s rank correlation test conducted between tumor grade and gene expression. A risk scoring system is developed based on IC30. We test the prognostic power of IC30 in the discovery and seven validation cohorts by both Cox proportional hazard regression and log-rank test. -
Investigating Unexplained Deaths for Molecular Autopsies
The author(s) shown below used Federal funding provided by the U.S. Department of Justice to prepare the following resource: Document Title: Investigating Unexplained Deaths for Molecular Autopsies Author(s): Yingying Tang, M.D., Ph.D, DABMG Document Number: 255135 Date Received: August 2020 Award Number: 2011-DN-BX-K535 This resource has not been published by the U.S. Department of Justice. This resource is being made publically available through the Office of Justice Programs’ National Criminal Justice Reference Service. Opinions or points of view expressed are those of the author(s) and do not necessarily reflect the official position or policies of the U.S. Department of Justice. Final Technical Report NIJ FY 11 Basic Science Research to Support Forensic Science 2011-DN-BX-K535 Investigating Unexplained Deaths through Molecular Autopsies May 28, 2017 Yingying Tang, MD, PhD, DABMG Principal Investigator Director, Molecular Genetics Laboratory Office of Chief Medical Examiner 421 East 26th Street New York, NY, 10016 Tel: 212-323-1340 Fax: 212-323-1540 Email: [email protected] Page 1 of 41 This resource was prepared by the author(s) using Federal funds provided by the U.S. Department of Justice. Opinions or points of view expressed are those of the author(s) and do not necessarily reflect the official position or policies of the U.S. Department of Justice. Abstract Sudden Unexplained Death (SUD) is natural death in a previously healthy individual whose cause remains undetermined after scene investigation, complete autopsy, and medical record review. SUD affects children and adults, devastating families, challenging medical examiners, and is a focus of research for cardiologists, neurologists, clinical geneticists, and scientists. -
Characterizing the Mechanisms of Kappa Opioid Receptor Signaling Within Mesolimbic Dopamine Circuitry Katie Reichard a Dissertat
Characterizing the mechanisms of kappa opioid receptor signaling within mesolimbic dopamine circuitry Katie Reichard A dissertation submitted in partial fulfillment of the degree requirements for the degree of: Doctor of Philosophy University of Washington 2020 Reading Committee: Charles Chavkin, Chair Paul Phillips Larry Zweifel Program Authorized to Confer Degree: Neuroscience Graduate Program TABLE OF CONTENTS Summary/Abstract………………………………………………………………………….……..6 Dedication……………………………………………………………………………….………...9 Chapter 1 The therapeutic potential of the targeting the kappa opioid receptor system in stress- associated mental health disorders……………………………….………………………………10 Section 1.1 Activation of the dynorphin/kappa opioid receptor system is associated with dysphoria, cognitive disruption, and increased preference for drugs of abuse…………………..13 Section 1.2 Contribution of the dyn/KOR system to substance use disorder, anxiety, and depression………………………………………………………………………………………..15 Section 1.3 KORs are expressed on dorsal raphe serotonin neurons and contribute to stress- induced plasticity with serotonin circuitry……………………………………………………….17 Section 1.4 Kappa opioid receptor expression in the VTA contributes to the behavioral response to stress……………………………………………………………………………………....…..19 Section 1.5 Other brain regions contributing to the KOR-mediated response to stress…………23 Section 1.6 G Protein signaling at the KOR …………………………………………………….25 Chapter 2: JNK-Receptor Inactivation Affects D2 Receptor through both agonist action and norBNI-mediated cross-inactivation -
The Chondrocyte Channelome: a Novel Ion Channel Candidate in the Pathogenesis of Pectus Deformities
Old Dominion University ODU Digital Commons Biological Sciences Theses & Dissertations Biological Sciences Summer 2017 The Chondrocyte Channelome: A Novel Ion Channel Candidate in the Pathogenesis of Pectus Deformities Anthony J. Asmar Old Dominion University, [email protected] Follow this and additional works at: https://digitalcommons.odu.edu/biology_etds Part of the Biology Commons, Molecular Biology Commons, and the Physiology Commons Recommended Citation Asmar, Anthony J.. "The Chondrocyte Channelome: A Novel Ion Channel Candidate in the Pathogenesis of Pectus Deformities" (2017). Doctor of Philosophy (PhD), Dissertation, Biological Sciences, Old Dominion University, DOI: 10.25777/pyha-7838 https://digitalcommons.odu.edu/biology_etds/19 This Dissertation is brought to you for free and open access by the Biological Sciences at ODU Digital Commons. It has been accepted for inclusion in Biological Sciences Theses & Dissertations by an authorized administrator of ODU Digital Commons. For more information, please contact [email protected]. THE CHONDROCYTE CHANNELOME: A NOVEL ION CHANNEL CANDIDATE IN THE PATHOGENESIS OF PECTUS DEFORMITIES by Anthony J. Asmar B.S. Biology May 2010, Virginia Polytechnic Institute M.S. Biology May 2013, Old Dominion University A Dissertation Submitted to the Faculty of Old Dominion University in Partial Fulfillment of the Requirements for the Degree of DOCTOR OF PHILOSOPHY BIOMEDICAL SCIENCES OLD DOMINION UNIVERSITY August 2017 Approved by: Christopher Osgood (Co-Director) Michael Stacey (Co-Director) Lesley Greene (Member) Andrei Pakhomov (Member) Jing He (Member) ABSTRACT THE CHONDROCYTE CHANNELOME: A NOVEL ION CHANNEL CANDIDATE IN THE PATHOGENESIS OF PECTUS DEFORMITIES Anthony J. Asmar Old Dominion University, 2017 Co-Directors: Dr. Christopher Osgood Dr. Michael Stacey Costal cartilage is a type of rod-like hyaline cartilage connecting the ribs to the sternum. -
Atrial Fibrillation (ATRIA) Study
European Journal of Human Genetics (2014) 22, 297–306 & 2014 Macmillan Publishers Limited All rights reserved 1018-4813/14 www.nature.com/ejhg REVIEW Atrial fibrillation: the role of common and rare genetic variants Morten S Olesen*,1,2,4, Morten W Nielsen1,2,4, Stig Haunsø1,2,3 and Jesper H Svendsen1,2,3 Atrial fibrillation (AF) is the most common cardiac arrhythmia affecting 1–2% of the general population. A number of studies have demonstrated that AF, and in particular lone AF, has a substantial genetic component. Monogenic mutations in lone and familial AF, although rare, have been recognized for many years. Presently, mutations in 25 genes have been associated with AF. However, the complexity of monogenic AF is illustrated by the recent finding that both gain- and loss-of-function mutations in the same gene can cause AF. Genome-wide association studies (GWAS) have indicated that common single-nucleotide polymorphisms (SNPs) have a role in the development of AF. Following the first GWAS discovering the association between PITX2 and AF, several new GWAS reports have identified SNPs associated with susceptibility of AF. To date, nine SNPs have been associated with AF. The exact biological pathways involving these SNPs and the development of AF are now starting to be elucidated. Since the first GWAS, the number of papers concerning the genetic basis of AF has increased drastically and the majority of these papers are for the first time included in a review. In this review, we discuss the genetic basis of AF and the role of both common and rare genetic variants in the susceptibility of developing AF. -
Renal Membrane Transport Proteins and the Transporter Genes
Techno e lo n g Gowder, Gene Technology 2014, 3:1 e y G Gene Technology DOI; 10.4172/2329-6682.1000e109 ISSN: 2329-6682 Editorial Open Access Renal Membrane Transport Proteins and the Transporter Genes Sivakumar J T Gowder* Qassim University, College of Applied Medical Sciences, Buraidah, Kingdom of Saudi Arabia Kidney this way, high sodium diet favors urinary sodium concentration [9]. AQP2 has a role in hereditary and acquired diseases affecting urine- In humans, the kidneys are a pair of bean-shaped organs about concentrating mechanisms [10]. AQP2 regulates antidiuretic action 10 cm long and located on either side of the vertebral column. The of arginine vasopressin (AVP). The urinary excretion of this protein is kidneys constitute for less than 1% of the weight of the human body, considered to be an index of AVP signaling activity in the renal system. but they receive about 20% of blood pumped with each heartbeat. The Aquaporins are also considered as markers for chronic renal allograft renal artery transports blood to be filtered to the kidneys, and the renal dysfunction [11]. vein carries filtered blood away from the kidneys. Urine, the waste fluid formed within the kidney, exits the organ through a duct called the AQP4 ureter. The kidney is an organ of excretion, transport and metabolism. This gene encodes a member of the aquaporin family of intrinsic It is a complicated organ, comprising various cell types and having a membrane proteins. These proteins function as water-selective channels neatly designed three dimensional organization [1]. Due to structural in the plasma membrane.