Goblet Cell LRRC26 Regulates BK Channel Activation and Protects Against Colitis in Mice
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Emerging Roles for Multifunctional Ion Channel Auxiliary Subunits in Cancer T ⁎ Alexander S
Cell Calcium 80 (2019) 125–140 Contents lists available at ScienceDirect Cell Calcium journal homepage: www.elsevier.com/locate/ceca Emerging roles for multifunctional ion channel auxiliary subunits in cancer T ⁎ Alexander S. Hawortha,b, William J. Brackenburya,b, a Department of Biology, University of York, Heslington, York, YO10 5DD, UK b York Biomedical Research Institute, University of York, Heslington, York, YO10 5DD, UK ARTICLE INFO ABSTRACT Keywords: Several superfamilies of plasma membrane channels which regulate transmembrane ion flux have also been Auxiliary subunit shown to regulate a multitude of cellular processes, including proliferation and migration. Ion channels are Cancer typically multimeric complexes consisting of conducting subunits and auxiliary, non-conducting subunits. Calcium channel Auxiliary subunits modulate the function of conducting subunits and have putative non-conducting roles, further Chloride channel expanding the repertoire of cellular processes governed by ion channel complexes to processes such as trans- Potassium channel cellular adhesion and gene transcription. Given this expansive influence of ion channels on cellular behaviour it Sodium channel is perhaps no surprise that aberrant ion channel expression is a common occurrence in cancer. This review will − focus on the conducting and non-conducting roles of the auxiliary subunits of various Ca2+,K+,Na+ and Cl channels and the burgeoning evidence linking such auxiliary subunits to cancer. Several subunits are upregu- lated (e.g. Cavβ,Cavγ) and downregulated (e.g. Kvβ) in cancer, while other subunits have been functionally implicated as oncogenes (e.g. Navβ1,Cavα2δ1) and tumour suppressor genes (e.g. CLCA2, KCNE2, BKγ1) based on in vivo studies. The strengthening link between ion channel auxiliary subunits and cancer has exposed these subunits as potential biomarkers and therapeutic targets. -
Variants in the KCNE1 Or KCNE3 Gene and Risk of Ménière’S Disease: a Meta-Analysis
Journal of Vestibular Research 25 (2015) 211–218 211 DOI 10.3233/VES-160569 IOS Press Variants in the KCNE1 or KCNE3 gene and risk of Ménière’s disease: A meta-analysis Yuan-Jun Li, Zhan-Guo Jin and Xian-Rong Xu∗ The Center of Clinical Aviation Medicine, General Hospital of Air Force, Beijing, China Received 1 August 2015 Accepted 8 December 2015 Abstract. BACKGROUND: Ménière’s disease (MD) is defined as an idiopathic disorder of the inner ear characterized by the triad of tinnitus, vertigo, and sensorineural hearing loss. Although many studies have evaluated the association between variants in the KCNE1 or KCNE3 gene and MD risk, debates still exist. OBJECTIVE: Our aim is to evaluate the association between KCNE gene variants, including KCNE1 rs1805127 and KCNE3 rs2270676, and the risk of MD by a systematic review. METHODS: We searched the literature in PubMed, SCOPUS and EMBASE through May 2015. We calculated pooled odds ra- tios (OR) and 95% confidence intervals (CIs) using a fixed-effects model or a random-effects model for the risk to MD associated with different KCNE gene variants. The heterogeneity assumption decided the effect model. RESULTS: A total of three relevant studies, with 302 MD cases and 515 controls, were included in this meta-analysis. The results indicated that neither the KCNE1 rs1805127 variant (for G vs. A: OR = 0.724, 95%CI 0.320, 1.638, P = 0.438), nor the KCNE3 rs2270676 variant (for T vs. C: OR = 0.714, 95%CI 0.327, 1.559, P = 0.398) was associated with MD risk. -
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. -
Non-Coding Rnas in the Cardiac Action Potential and Their Impact on Arrhythmogenic Cardiac Diseases
Review Non-Coding RNAs in the Cardiac Action Potential and Their Impact on Arrhythmogenic Cardiac Diseases Estefania Lozano-Velasco 1,2 , Amelia Aranega 1,2 and Diego Franco 1,2,* 1 Cardiovascular Development Group, Department of Experimental Biology, University of Jaén, 23071 Jaén, Spain; [email protected] (E.L.-V.); [email protected] (A.A.) 2 Fundación Medina, 18016 Granada, Spain * Correspondence: [email protected] Abstract: Cardiac arrhythmias are prevalent among humans across all age ranges, affecting millions of people worldwide. While cardiac arrhythmias vary widely in their clinical presentation, they possess shared complex electrophysiologic properties at cellular level that have not been fully studied. Over the last decade, our current understanding of the functional roles of non-coding RNAs have progressively increased. microRNAs represent the most studied type of small ncRNAs and it has been demonstrated that miRNAs play essential roles in multiple biological contexts, including normal development and diseases. In this review, we provide a comprehensive analysis of the functional contribution of non-coding RNAs, primarily microRNAs, to the normal configuration of the cardiac action potential, as well as their association to distinct types of arrhythmogenic cardiac diseases. Keywords: cardiac arrhythmia; microRNAs; lncRNAs; cardiac action potential Citation: Lozano-Velasco, E.; Aranega, A.; Franco, D. Non-Coding RNAs in the Cardiac Action Potential 1. The Electrical Components of the Adult Heart and Their Impact on Arrhythmogenic The adult heart is a four-chambered organ that propels oxygenated blood to the entire Cardiac Diseases. Hearts 2021, 2, body. It is composed of atrial and ventricular chambers, each of them with distinct left and 307–330. -
Anoctamin 1 (Tmem16a) Ca -Activated Chloride Channel Stoichiometrically Interacts with an Ezrin–Radixin–Moesin Network
Anoctamin 1 (Tmem16A) Ca2+-activated chloride channel stoichiometrically interacts with an ezrin–radixin–moesin network Patricia Perez-Cornejoa,1, Avanti Gokhaleb,1, Charity Duranb,1, Yuanyuan Cuib, Qinghuan Xiaob, H. Criss Hartzellb,2, and Victor Faundezb,2 aPhysiology Department, School of Medicine, Universidad Autónoma de San Luis Potosí, San Luis Potosí, SLP 78210, Mexico; and bDepartment of Cell Biology, Emory University School of Medicine, Atlanta, GA 30322 Edited by David E. Clapham, Howard Hughes Medical Institute, Children’s Hospital Boston, Boston, MA, and approved May 9, 2012 (received for review January 4, 2012) The newly discovered Ca2+-activated Cl− channel (CaCC), Anocta- approach to identify Ano1-interacting proteins. We find that min 1 (Ano1 or TMEM16A), has been implicated in vital physiolog- Ano1 forms a complex with two high stochiometry interactomes. ical functions including epithelial fluid secretion, gut motility, and One protein network is centered on the signaling/scaffolding smooth muscle tone. Overexpression of Ano1 in HEK cells or Xen- actin-binding regulatory proteins ezrin, radixin, moesin, and opus oocytes is sufficient to generate Ca2+-activated Cl− currents, RhoA. The ezrin–radixin–moesin (ERM) proteins organize the but the details of channel composition and the regulatory factors cortical cytoskeleton by linking actin to the plasma membrane that control channel biology are incompletely understood. We and coordinate cell signaling events by scaffolding signaling used a highly sensitive quantitative SILAC proteomics approach molecules (19). The other major interactome is centered on the to obtain insights into stoichiometric protein networks associated SNARE and SM proteins VAMP3, syntaxins 2 and -4, and the with the Ano1 channel. -
Ion Channels of Nociception
International Journal of Molecular Sciences Editorial Ion Channels of Nociception Rashid Giniatullin A.I. Virtanen Institute, University of Eastern Finland, 70211 Kuopio, Finland; Rashid.Giniatullin@uef.fi; Tel.: +358-403553665 Received: 13 May 2020; Accepted: 15 May 2020; Published: 18 May 2020 Abstract: The special issue “Ion Channels of Nociception” contains 13 articles published by 73 authors from different countries united by the main focusing on the peripheral mechanisms of pain. The content covers the mechanisms of neuropathic, inflammatory, and dental pain as well as pain in migraine and diabetes, nociceptive roles of P2X3, ASIC, Piezo and TRP channels, pain control through GPCRs and pharmacological agents and non-pharmacological treatment with electroacupuncture. Keywords: pain; nociception; sensory neurons; ion channels; P2X3; TRPV1; TRPA1; ASIC; Piezo channels; migraine; tooth pain Sensation of pain is one of the fundamental attributes of most species, including humans. Physiological (acute) pain protects our physical and mental health from harmful stimuli, whereas chronic and pathological pain are debilitating and contribute to the disease state. Despite active studies for decades, molecular mechanisms of pain—especially of pathological pain—remain largely unaddressed, as evidenced by the growing number of patients with chronic forms of pain. There are, however, some very promising advances emerging. A new field of pain treatment via neuromodulation is quickly growing, as well as novel mechanistic explanations unleashing the efficiency of traditional techniques of Chinese medicine. New molecular actors with important roles in pain mechanisms are being characterized, such as the mechanosensitive Piezo ion channels [1]. Pain signals are detected by specialized sensory neurons, emitting nerve impulses encoding pain in response to noxious stimuli. -
Ion Channels 3 1
r r r Cell Signalling Biology Michael J. Berridge Module 3 Ion Channels 3 1 Module 3 Ion Channels Synopsis Ion channels have two main signalling functions: either they can generate second messengers or they can function as effectors by responding to such messengers. Their role in signal generation is mainly centred on the Ca2 + signalling pathway, which has a large number of Ca2+ entry channels and internal Ca2+ release channels, both of which contribute to the generation of Ca2 + signals. Ion channels are also important effectors in that they mediate the action of different intracellular signalling pathways. There are a large number of K+ channels and many of these function in different + aspects of cell signalling. The voltage-dependent K (KV) channels regulate membrane potential and + excitability. The inward rectifier K (Kir) channel family has a number of important groups of channels + + such as the G protein-gated inward rectifier K (GIRK) channels and the ATP-sensitive K (KATP) + + channels. The two-pore domain K (K2P) channels are responsible for the large background K current. Some of the actions of Ca2 + are carried out by Ca2+-sensitive K+ channels and Ca2+-sensitive Cl − channels. The latter are members of a large group of chloride channels and transporters with multiple functions. There is a large family of ATP-binding cassette (ABC) transporters some of which have a signalling role in that they extrude signalling components from the cell. One of the ABC transporters is the cystic − − fibrosis transmembrane conductance regulator (CFTR) that conducts anions (Cl and HCO3 )and contributes to the osmotic gradient for the parallel flow of water in various transporting epithelia. -
1 Molecular and Genetic Regulation of Pig Pancreatic Islet Cell Development 2 3 4 Seokho Kim1,9, Robert L
bioRxiv preprint doi: https://doi.org/10.1101/717090; this version posted January 24, 2020. 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. 1 Molecular and genetic regulation of pig pancreatic islet cell development 2 3 4 Seokho Kim1,9, Robert L. Whitener1,9, Heshan Peiris1, Xueying Gu1, Charles A. Chang1, 5 Jonathan Y. Lam1, Joan Camunas-Soler2, Insung Park3, Romina J. Bevacqua1, Krissie Tellez1, 6 Stephen R. Quake2,4, Jonathan R. T. Lakey5, Rita Bottino6, Pablo J. Ross3, Seung K. Kim1,7,8 7 8 1Department of Developmental Biology, Stanford University School of Medicine, 9 Stanford, CA, 94305 USA 10 2Department of Bioengineering, Stanford University, Stanford, CA, 94305 USA 11 3Department of Animal Science, University of California Davis, Davis, CA, 95616 USA 12 4Chan Zuckerberg Biohub, San Francisco, CA 94518, USA. 13 5Department of Surgery, University of California at Irvine, Irvine, CA, 92868 USA 14 6Institute of Cellular Therapeutics, Allegheny Health Network, Pittsburgh, PA, 15212 USA 15 7Department of Medicine, Stanford University School of Medicine, Stanford, CA, 94305 USA 16 8Stanford Diabetes Research Center, Stanford University School of Medicine, 17 Stanford, CA, 94305 USA 18 19 9These authors contributed equally 20 21 Correspondence and requests for materials should be addressed to S.K.K (email: 22 [email protected]) 23 24 Key Words: pancreas; metabolism; organogenesis; b-cell; a-cell; d-cell; diabetes mellitus 25 26 Summary Statement: This study reveals transcriptional, signaling and cellular programs 27 governing pig pancreatic islet development, including striking similarities to human islet 28 ontogeny, providing a novel resource for advancing human islet replacement strategies. -
Figure S1. Development of YK Resistant Cell Lines. (A) A4573-R Tolerated a Maximum YK Concentration of 3.475 Μm with the Most Recent IC50 Value of 14.90 Μm
Figure S1. Development of YK resistant cell lines. (A) A4573-R tolerated a maximum YK concentration of 3.475 µM with the most recent IC50 value of 14.90 µM. (B) TC71-R tolerated a maximum YK concentration of 0.876 µM with the most recent IC50 value of 1.857 µM. Drops in YK concentration in media represent the time points at which resistant cells were frozen and thawed. YK, YK-4-279; R, resistant. Figure S2. Viability curves comparing sensitive and resistant TC71 cell lines with (A) YK, (B) doxorubicin, (C) etoposide and (D) vincristine. IC50 values are presented. Resistant cells demonstrated significantly reduced sensitivity to YK (P<0.0001 vs. sensitive). YK resistant cells were significantly also resistant doxorubicin (P<0.0001 vs. sensitive), but did not demonstrate cross-resistance to etoposide or vincristine. YK, YK-4-279. Figure S3. CD99 expression is increased in TC71-R cells. (A) Quantitative PCR analysis for EF, CD99 and 18S ribosomal RNA in TC71 sensitive cells and resistant cells at multiple time points. CD99 RNA expression is significantly elevated when compared with sensitive cells at all time points. ***P<0.001 and ****P<0.0001 vs. sensitive. (B) Western blot analysis of CD99 and EF in TC71 sensitive and resistant cells. Expression levels were calculated using densitometry analysis relative to sensitive cell lines. EF, EWS-FLI1. Figure S4. Quantitative PCR for upregulated genes identified through RNA sequencing in TC71 cells. Relative expres- sion was evaluated at multiple time points in resistant cells compared with sensitive cell expression. (A) Upregulated genes included ANO1, BRSK2 and IGSF21. -
The Influence of the Pharmaceutical Industry on Medicine, As Exemplified by Proton Pump Inhibitors
The Influence of the Pharmaceutical Industry on Medicine, as Exemplified by Proton Pump Inhibitors The Influence of the Pharmaceutical Industry on Medicine, as Exemplified by Proton Pump Inhibitors By Helge L. Waldum The Influence of the Pharmaceutical Industry on Medicine, as Exemplified by Proton Pump Inhibitors By Helge L. Waldum This book first published 2020 Cambridge Scholars Publishing Lady Stephenson Library, Newcastle upon Tyne, NE6 2PA, UK British Library Cataloguing in Publication Data A catalogue record for this book is available from the British Library Copyright © 2020 by Helge L. Waldum All rights for this book reserved. No part of this book may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, without the prior permission of the copyright owner. ISBN (10): 1-5275-5882-7 ISBN (13): 978-1-5275-5882-3 CONTENTS Acknowledgements .................................................................................. vii Preface ....................................................................................................... ix Chapter 1 .................................................................................................... 1 Background References ............................................................................................. 7 Chapter 2 .................................................................................................... 9 Gastric Juice and its Function Regulation of gastric acid secretion -
The Relationship Between Duodenal Enterochromaffin Cell Distribution
The Relationship Between Duodenal Enterochromaffin Cell Distribution and Degree of Inflammatory Bowel Disease (IBD) In Dogs 1 2 2 2 3 2 2 Twito, R., Famigli Bergamini,, P., Galiazzo, G., Peli, A., Cocchi, M., Bettini, G., Chiocchetti, R., Bresciani, F.2 and Pietra, M.2 * 1 Private Practitioner, Tierklinik Dr. Krauß, Düsseldorf GmbH, Germany. 2 Departement of Veterinary Medical Sciences, School of Agriculture and Veterinary Medicine, University of Bologna, Ozzano dell’Emilia (BO), Italy. 3 L.U.DE.S. University, Lugano, Switzerland. * Corresponding Author: Prof. Marco Pietra, University of Bologna, School of Agriculture and Veterinary Medicine, Department of Veterinary Medical Sciences, Ozzano dell’Emilia (BO), Italy. Tel.+39 051 20 9 7303, Fax +39 051 2097038. Email: [email protected] ABSTRACT Despite numerous studies carried out over the last 15 years in veterinary medicine, the pathogenesis of canine Inflammatory Bowel Disease (IBD) has still not been completely elucidated. In particular, unlike what has been demonstrated in human medicine, the influence of serotonin on clinical signs in canine IBD has not yet been clarified. The objective of this paper has been to seek a possible correlation between duodenal epithelial distribution of serotonin-producing cells (enterochromaffin cells) and disease-grading parameters (clinical, clinico-pathological, endoscopic and histopathological) in dogs with IBD. The medical records of dogs with a diagnosis of IBD were retrospectively reviewed and 21 client-owned dogs with a diagnosis of IBD were registered. Clinical score (by Canine Chronic Enteropathy Clinical Activity Index), laboratory examinations (albumin, total cholesterol, folate, cobalamin), endoscopic score and histopathological score, were compared by regression analysis with duodenal enterochromaffin cell percentage. -
Distinct Subdomains of the KCNQ1 S6 Segment Determine Channel Modulation by Different KCNE Subunits
ARTICLE Distinct subdomains of the KCNQ1 S6 segment determine channel modulation by different KCNE subunits Carlos G. Vanoye,1 Richard C. Welch,1 Melissa A. Daniels,1 Lauren J. Manderfield,2 Andrew R. Tapper,2 Charles R. Sanders,3 and Alfred L. George Jr.1,2 1Division of Genetic Medicine, Department of Medicine, 2Department of Pharmacology, and 3Department of Biochemistry, Center for Structural Biology, Vanderbilt University, Nashville, TN 37232 Modulation of voltage-gated potassium (KV) channels by the KCNE family of single transmembrane proteins has physiological and pathophysiological importance. All five KCNE proteins (KCNE1–KCNE5) have been demon- strated to modulate heterologously expressed KCNQ1 (KV7.1) with diverse effects, making this channel a valuable experimental platform for elucidating structure–function relationships and mechanistic differences among mem- bers of this intriguing group of accessory subunits. Here, we specifically investigated the determinants of KCNQ1 inhibition by KCNE4, the least well-studied KCNE protein. In CHO-K1 cells, KCNQ1, but not KCNQ4, is strongly inhibited by coexpression with KCNE4. By studying KCNQ1-KCNQ4 chimeras, we identified two adjacent residues (K326 and T327) within the extracellular end of the KCNQ1 S6 segment that determine inhibition of KCNQ1 by KCNE4. This dipeptide motif is distinct from neighboring S6 sequences that enable modulation by KCNE1 and KCNE3. Conversely, S6 mutations (S338C and F340C) that alter KCNE1 and KCNE3 effects on KCNQ1 do not ab- rogate KCNE4 inhibition. Further, KCNQ1-KCNQ4 chimeras that exhibited resistance to the inhibitory effects of KCNE4 still interact biochemically with this protein, implying that accessory subunit binding alone is not sufficient for channel modulation.