DOCSLIB.ORG

The Chromogranin A-Derived Peptides Catestatin and Vasostatin in Dogs

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
The Chromogranin A-Derived Peptides Catestatin and Vasostatin in Dogs Höglund et al. Acta Vet Scand (2020) 62:43 https://doi.org/10.1186/s13028-020-00541-3 Acta Veterinaria Scandinavica RESEARCH Open Access The chromogranin A-derived peptides catestatin and vasostatin in dogs with myxomatous mitral valve disease Katja Höglund1* , Jens Häggström2 , Odd Viking Höglund2 , Mats Stridsberg3 , Anna Tidholm2,4 and Ingrid Ljungvall2 Abstract Background: The protein chromogranin A (CgA) is stored and co-released with catecholamines from the stimulated adrenal glands. Increased plasma concentrations of CgA have been shown in people with heart disease. The aim of the study was to investigate whether plasma concentrations of the CgA-derived biologically active peptides catesta- tin and vasostatin were associated with the severity of myxomatous mitral valve disease (MMVD) in dogs and to assess potential associations between these blood variables and dog characteristics, echocardiographic variables, heart rate (HR), blood pressure (BP) and plasma N-terminal-proBNP (NT-proBNP) concentration. Sixty-seven privately owned dogs with or without MMVD were included. The dogs underwent physical examination, blood pressure measurement, blood sample collection, and echocardiographic examination. Plasma concentrations of catestatin and vasostatin were analyzed using radioimmunoassay. Results: Catestatin concentration decreased with increasing left atrial and ventricular size (R 2 0.09, P 0.019), and increased with increasing systolic and diastolic blood pressures (R2 0.08, P 0.038). Regression≤ analyses≤ showed no signifcant associations for vasostatin. No diferences in plasma concentrations≤ ≤ of catestatin or vasostatin were found between the disease severity groups used in the study. Conclusions: In the present dog population, the catestatin concentration showed weak negative associations with left atrial and ventricular sizes, both of which are known to increase with increasing severity of MMVD. Furthermore, the catestatin concentration showed weak positive associations with blood pressure. Keywords: Canine, Catestatin, Heart, Sympathetic nervous system, Vasostatin Background cells of the adrenal medulla. Chromogranin A co-exists Chromogranin A (CgA) is an acidic, soluble secretory in secretory granules with catecholamines, with which protein, belonging to the granin family. Te protein has it is co-released during exocytosis [1–3]. Chromogranin a widespread distribution in neuroendocrine and endo- A is also produced in the human myocardium and has crine tissues as well as in the central and peripheral been found co-localized with B-type natriuretic peptide nervous systems, and is also abundant in the chromafn (BNP) in the myocardium of people with heart disease [4]. Chromogranin A is a precursor of several biologically active peptides, including catestatin and vasostatin [5], *Correspondence: [email protected] which modulate cardiac hemodynamics during adrener- 1 Department of Anatomy, Physiology and Biochemistry, Faculty gic stimulation and seem to protect the cardiovascular of Veterinary Medicine and Animal Science, Swedish University of Agricultural Sciences, 750 07 Uppsala, Sweden system against excessive beta-adrenergic stimulation [6]. Full list of author information is available at the end of the article © The Author(s) 2020. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creat iveco mmons .org/licen ses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creat iveco mmons .org/publi cdoma in/ zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Höglund et al. Acta Vet Scand (2020) 62:43 Page 2 of 7 In contrast to catecholamines, which degrade rapidly in of cardiac disease. Dogs in need of heart failure therapy plasma [7], CgA has a high stability [8] and is considered were allowed into the study. Dogs with congenital heart a useful marker of sympathetic nervous activation [9, disease, other acquired cardiovascular disorders or signif- 10]. In people, plasma CgA has been shown to increase icant organ-related or systemic diseases were excluded. in situations of pronounced sympathetic stimulation such as in critically ill patients [11]. High plasma CgA Examinations concentrations have been found in people with conges- Dogs underwent physical examination, blood pressure tive heart failure (CHF) due to coronary artery disease, measurement, blood sample collection, and echocardio- arterial hypertension, dilated cardiomyopathy (DCM), graphic examination, all performed during the same con- hypertrophic cardiomyopathy and valvular disease [4, sultation. Blood pressure was indirectly measured using 12–14] and plasma CgA concentration has been shown an automated oscillometric device (Vet HDO monitor, to increase with increasing severity of diferent human S + B med Vet GmbH, Babenhausen, Germany). Once cardiac diseases [12]. Furthermore, studies in people reliable consecutive readings were obtained, fve con- with acute myocardial infarction have shown increased secutive blood pressure recordings were performed and catestatin concentrations in plasma [15–17] as well as the mean was calculated. Blood was collected by jugular in serum [18], while one study showed decreased serum venipuncture into EDTA-tubes; plasma was separated by vasostatin-2 concentrations in patients with chronic centrifugation within 30 min of collection, transferred heart failure due to previous myocardial infarction, com- to plastic cryotubes and stored at − 80 °C for batched pared to in healthy controls [19]. analysis. In dogs, myxomatous mitral valve disease (MMVD) Echocardiography, performed by an ultrasonographic is the most common heart disease [20–22]. Te disease unit (iE33, Philips Ultrasound, Bothell, WA, USA), was is characterized by slow progressive degeneration of the used to verify the diagnosis of MMVD and to exclude mitral valve apparatus, leading to mitral regurgitation other cardiac diseases. Assessment of mitral valve struc- (MR). With progressive degeneration of the valve leafets, tures was performed and degree of MR was assessed the regurgitation increases, leading to volume overload by color Doppler. Te MR was subjectively assessed as and subsequent dilation of the left atrium and ventricle, the area of regurgitant jet relative to the area of the left and risk of developing CHF [20, 23]. During progression atrium [29] with slight modifcations [30]. Measurements of the disease, neuroendocrine activation takes place [24, of the left ventricle (fve consecutive cardiac cycles) and 25], and increased plasma norepinephrine concentra- left atrial to aortic root (LA/Ao) ratio (three consecutive tions have been found in dogs with DCM and in dogs cardiac cycles) were performed as previously described with advanced MMVD [26, 27]. [31, 32]. Te mean value for each variable was used in Plasma concentrations of CgA or derived peptides have the statistical analyses. Diagnostic criteria for MMVD not been investigated in dogs with heart disease. A radio- included characteristic 2-dimensional valvular lesions immunoassay (RIA) for measurement of the peptides cat- of the mitral valve apparatus (thickened and/or prolaps- estatin and vasostatin, which both have cardiovascular ing mitral valve leafets) and demonstrated MR by color functions [5], has been validated for canine plasma [28]. Doppler [29, 33]. Estimation of MMVD severity was Hence, the aims of the present study were to investigate based on obtained LA/Ao ratio and MR jet size, and dogs whether plasma concentrations of catestatin and vasosta- were classifed as follows: Healthy (LA/Ao < 1.5 and non tin were associated with severity of MMVD in dogs and to minimal MR jet), mild (LA/Ao ≤ 1.5 and MR jet < 30%), to assess potential associations between plasma concen- moderate (LA/Ao < 1.8 and MR jet ≤ 50%), and severe trations of catestatin and vasostatin and dog characteris- (LA/Ao ≥ 1.8 and MR jet > 50%) MMVD [30, 34, 35]. Val- tics, echocardiographic variables, heart rate (HR), blood ues for percent increases of end-diastolic left ventricular pressure (BP) and plasma N-terminal-proBNP (NT- internal dimension (LVIDdinc) and end-systolic left ven- proBNP) concentration. tricular internal dimension (LVIDsinc) were calculated as previously described [30, 36]. Methods Animals Analyses of catestatin and vasostatin Client-owned dogs were examined at the cardiology Analyses of plasma catestatin and vasostatin concentra- unit at the University Teaching Hospital of the Swed- tions were performed by RIAs specifc for catestatin and ish University of Agricultural Sciences in Uppsala, vasostatin [37, 38], validated for use in dogs [28]. Te Sweden according to a pre-specifed protocol. To be coefcient of variation was 3.6% and 8.8% for catesta- included, dogs had to either have evidence
Load more

Recommended publications
  • Uncorrected Author Proof Boller Et Al
    Journal of Parkinson’s Disease xx (2020) x–xx 1 DOI 10.3233/JPD-202323 IOS Press 1 Review 2 Neuropathological and Biomarker Findings 3 in Parkinson’s Disease and Alzheimer’s 4 Disease: From Protein Aggregates to 5 Synaptic Dysfunction a,b,∗ c,d,e,∗ 6 Yaroslau Compta and Tamas Revesz a 7 Parkinson’s disease & Movement Disorders Unit, Neurology Service, Hospital Cl´ınic / IDIBAPS / CIBERNED, 8 Barcelona, Catalonia, Spain b 9 Institut de Neuroci`encies, Maextu’s excellence center, University of Barcelona, Barcelona, Catalonia, Spain c 10 Queen Square Brain Bank for Neurological Disorders, Department of Clinical and Movement Neurosciences, 11 UCL Queen Square Institute of Neurology, University College London, UK d 12 Reta Lila Weston Institute of Neurological Studies, UCL Institute of Neurology, London, UK 13 eDepartment of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, University College 14 London, UK Accepted 9 November 2020 15 Abstract. 16 There is mounting evidence that Parkinson’s disease (PD) and Alzheimer’s disease (AD) share neuropathological hallmarks, 17 while similar types of biomarkers are being applied to both. In this review we aimed to explore similarities and differences 18 between PD and AD at both the neuropathology and the biomarker levels, specifically focusing on protein aggregates 19 and synapse dysfunction. Thus, amyloid-␤ peptide (A␤) and tau lesions of the Alzheimer-type are common in PD and 20 ␣-synuclein Lewy-type aggregates are frequent findings in AD. Modern neuropathological techniques adding to routine 21 immunohistochemistry might take further our knowledge of these diseases beyond protein aggregates and down to their 22 presynaptic and postsynaptic terminals, with potential mechanistic and even future therapeutic implications.
    [Show full text]
  • Limited Diagnostic Utility of Chromogranin a Measurements in Workup of Neuroendocrine Tumors
    diagnostics Article Limited Diagnostic Utility of Chromogranin A Measurements in Workup of Neuroendocrine Tumors Jonas Baekdal 1,2,*, Jesper Krogh 1,2, Marianne Klose 1,2, Pernille Holmager 1,2, Seppo W. Langer 1,3, Peter Oturai 1,4,5, Andreas Kjaer 1,4,5 , Birgitte Federspiel 1,6, Linda Hilsted 1,7, Jens F. Rehfeld 1,7, Ulrich Knigge 1,2,8 and Mikkel Andreassen 1,2 1 ENETS Neuroendocrine Tumor Centre of Excellence, Rigshospitalet, Copenhagen University Hospital, 2100 Copenhagen, Denmark; [email protected] (J.K.); [email protected] (M.K.); [email protected] (P.H.); [email protected] (S.W.L.); [email protected] (P.O.); [email protected] (A.K.); [email protected] (B.F.); [email protected] (L.H.); [email protected] (J.F.R.); [email protected] (U.K.); [email protected] (M.A.) 2 Department of Endocrinology, Rigshospitalet, Copenhagen University Hospital, 2100 Copenhagen, Denmark 3 Department of Oncology, Rigshospitalet, Copenhagen University Hospital, 2100 Copenhagen, Denmark 4 Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Copenhagen University Hospital, 2100 Copenhagen, Denmark 5 Department of Biomedical Sciences, Rigshospitalet and University of Copenhagen, 2100 Copenhagen, Denmark 6 Department of Pathology, Rigshospitalet, Copenhagen University Hospital, 2100 Copenhagen, Denmark 7 Department of Clinical Biochemistry, Rigshospitalet, Copenhagen University Hospital, 2100 Copenhagen, Denmark 8 Department of Surgery and Transplantation, Rigshospitalet, Copenhagen University Hospital, 2100 Copenhagen, Denmark * Correspondence: [email protected]; Tel.: +45-6013-4687 Received: 11 October 2020; Accepted: 28 October 2020; Published: 29 October 2020 Abstract: Background: Plasma chromogranin A (CgA) is related to tumor burden and recommended in the follow-up of patients diagnosed with neuroendocrine tumors (NETs).
    [Show full text]
  • Identification of VGF Nerve Growth Factor Inducible-Producing Cells In
    Int. J. Med. Sci. 2020, Vol. 17 480 Ivyspring International Publisher International Journal of Medical Sciences 2020; 17(4): 480-489. doi: 10.7150/ijms.39101 Research Paper Identification of VGF nerve growth factor inducible-producing cells in human spinal cords and expression change in patients with amyotrophic lateral sclerosis Yasuhiro Noda1, Miruto Tanaka1, Shinsuke Nakamura1, Junko Ito2, Akiyoshi Kakita2, Hideaki Hara1, and Masamitsu Shimazawa1 1. Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu 501-1196, Japan. 2. Department of Pathology, Brain Research Institute, Niigata University, Niigata, Japan. Corresponding author: Dr. Masamitsu Shimazawa, Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu 501-1196, Japan. E-mail: [email protected], Telephone and Fax: +81-58-230-8126 © The author(s). This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions. Received: 2019.08.06; Accepted: 2019.12.23; Published: 2020.02.04 Abstract Amyotrophic lateral sclerosis (ALS) is a serious disease characterized by the degeneration of motor neurons resulting in muscle weakness and paralysis. The neuroendocrine polypeptide VGF is localized in the central nervous system and peripheral endocrine neurons and is cleaved into several polypeptides with multiple functions. Previous studies revealed that VGF was decreased in the cerebrospinal fluid of ALS model mice and sporadic ALS patients. However, it is unknown which cells supply VGF in the spinal cord and a detailed localization is lacking.
    [Show full text]
  • The Granin Protein Family in Cardiac Disease
    The granin protein family in cardiac disease Helge R. Røsjø, MD1,2,3 1 Division of Medicine, Akershus University Hospital, Lørenskog, Norway 2 Institute of Experimental Medical Research, Oslo University Hospital, Ullevål, Oslo, Norway 3 Center for Heart Failure Research and K.G. Jebsen Cardiac Research Centre, Institute of Clinical Medicine, University of Oslo, Oslo, Norway © Helge R. Røsjø, 2012 Series of dissertations submitted to the Faculty of Medicine, University of Oslo No. 1333 ISBN 978-82-8264-359-7 All rights reserved. No part of this publication may be reproduced or transmitted, in any form or by any means, without permission. Cover: Inger Sandved Anfinsen. Printed in Norway: AIT Oslo AS. Produced in co-operation with Unipub. The thesis is produced by Unipub merely in connection with the thesis defence. Kindly direct all inquiries regarding the thesis to the copyright holder or the unit which grants the doctorate. Contents Supported by ......................................................................................................................... 4 Acknowledgments ................................................................................................................ 5 Abbreviations ........................................................................................................................ 8 List of papers in thesis: ....................................................................................................... 10 Introduction .......................................................................................................................
    [Show full text]
  • Chromogranin a Dependent Upon Interaction with Biogenesis in Mast
    Secretogranin III Directs Secretory Vesicle Biogenesis in Mast Cells in a Manner Dependent upon Interaction with Chromogranin A This information is current as of October 4, 2021. Prerna Prasad, Angel A. Yanagihara, Andrea L. Small-Howard, Helen Turner and Alexander J. Stokes J Immunol 2008; 181:5024-5034; ; doi: 10.4049/jimmunol.181.7.5024 http://www.jimmunol.org/content/181/7/5024 Downloaded from References This article cites 42 articles, 15 of which you can access for free at: http://www.jimmunol.org/content/181/7/5024.full#ref-list-1 http://www.jimmunol.org/ Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication by guest on October 4, 2021 *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2008 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology Secretogranin III Directs Secretory Vesicle Biogenesis in Mast Cells in a Manner Dependent upon Interaction with Chromogranin A1 Prerna Prasad,2*§ Angel A. Yanagihara,2‡ Andrea L. Small-Howard,2* Helen Turner,2,3*† and Alexander J.
    [Show full text]
  • 030320 the Chromogranin–Secretogranin Family
    The new england journal of medicine review article mechanisms of disease The Chromogranin–Secretogranin Family Laurent Taupenot, Ph.D., Kimberly L. Harper, M.D., and Daniel T. O’Connor, M.D. From the Department of Medicine (L.T., eurons and neuroendocrine cells contain membrane- K.L.H., D.T.O.) and the Center for Molecular delimited pools of peptide hormones, biogenic amines, and neurotransmit- Genetics (D.T.O.), University of California n at San Diego, La Jolla; and the Veterans ters with a characteristic electron-dense appearance on transmission electron Affairs San Diego Healthcare System, San microscopy (Fig. 1). These vesicles, which are present throughout the neuroendocrine Diego, Calif. (L.T., K.L.H., D.T.O.). Address system1,2 and in a variety of neurons, store and release chromogranins and secretogranins reprint requests to Dr. O’Connor at the 3,4 Department of Medicine (9111H), Univer- (also known as “granins”), a unique group of acidic, soluble secretory proteins. The sity of California at San Diego, 3350 La Jolla three “classic” granins are chromogranin A, which was first isolated from chromaffin Village Dr., San Diego, CA 92161, or at cells of the adrenal medulla5,6; chromogranin B, initially characterized in a rat pheochro- [email protected]. mocytoma cell line7; and secretogranin II (sometimes called chromogranin C), which 8,9 N Engl J Med 2003;348:1134-49. was originally described in the anterior pituitary. Four other acidic secretory pro- Copyright © 2003 Massachusetts Medical Society. teins were later proposed for membership in the granin family10: secretogranin III (or 1B1075),11 secretogranin IV (or HISL-19),12 secretogranin V (or 7B2),13 and secretogra- nin VI (or NESP55).14 In this article, we review aspects of the structures, biochemical properties, and clin- ical importance of granins, with particular emphasis on chromogranin A, the granin that was discovered first and that has been studied most extensively.
    [Show full text]
  • Ganglioneurofibroma Arising Within the Extralobar Pulmonary Sequestration Yuanyuan Liu1, Wenbin Wu2, Longbo Gong2 and Miao Zhang2*
    Liu et al. Journal of Cardiothoracic Surgery (2020) 15:252 https://doi.org/10.1186/s13019-020-01295-9 CASE REPORT Open Access Ganglioneurofibroma arising within the extralobar pulmonary sequestration Yuanyuan Liu1, Wenbin Wu2, Longbo Gong2 and Miao Zhang2* Abstract Background: Neurogenic tumor arising within the pulmonary sequestration (PS) is rare. Case presentation: A 42-year-old asymptomatic female was referred to our hospital for work-up of extralobar PS. The independent feeding artery from the thoracic aorta was confirmed by three-dimensional computed tomography angiography (3D-CTA). Uniportal thoracoscopic resection of the sequestrated lung with mediastinal lymph node sampling was performed successfully. Ganglioneurofibroma within the PS was diagnosed as the specimen revealed positive expression of SRY-related HMG-box 10 protein, neuron-specific enolase, S-100, chromogranin A and synuclein. Tumor recurrence was not recorded 1 year after the surgery. Conclusion: Preoperative 3D-CTA is useful to identify the aberrant vessels of PS. An elaborate diagnostic work-up after a timely resection is necessary for subsequent management and follow-up plan. Keywords: Pulmonary sequestration (PS), Three-dimensional computed tomography angiography (3D-CTA), Uniportal, Single port, Video-assisted thoracoscopic surgery (VATS) Background Case presentation Ganglioneuroma is a rare, benign and well-differentiated This report was approved by the Institutional Review neurogenic tumor, which is mostly localized in the pos- Board of Xuzhou Central Hospital, and written informed terior mediastinum [1]. It usually grows very slow and consent was obtained from the patient. The clinical data displaces the surrounding anatomical structures without was presented anonymously for privacy concern. A 42- infiltration [2].
    [Show full text]
  • 1 1 2 3 Cell Type-Specific Transcriptomics of Hypothalamic
    1 2 3 4 Cell type-specific transcriptomics of hypothalamic energy-sensing neuron responses to 5 weight-loss 6 7 Fredrick E. Henry1,†, Ken Sugino1,†, Adam Tozer2, Tiago Branco2, Scott M. Sternson1,* 8 9 1Janelia Research Campus, Howard Hughes Medical Institute, 19700 Helix Drive, Ashburn, VA 10 20147, USA. 11 2Division of Neurobiology, Medical Research Council Laboratory of Molecular Biology, 12 Cambridge CB2 0QH, UK 13 14 †Co-first author 15 *Correspondence to: [email protected] 16 Phone: 571-209-4103 17 18 Authors have no competing interests 19 1 20 Abstract 21 Molecular and cellular processes in neurons are critical for sensing and responding to energy 22 deficit states, such as during weight-loss. AGRP neurons are a key hypothalamic population 23 that is activated during energy deficit and increases appetite and weight-gain. Cell type-specific 24 transcriptomics can be used to identify pathways that counteract weight-loss, and here we 25 report high-quality gene expression profiles of AGRP neurons from well-fed and food-deprived 26 young adult mice. For comparison, we also analyzed POMC neurons, an intermingled 27 population that suppresses appetite and body weight. We find that AGRP neurons are 28 considerably more sensitive to energy deficit than POMC neurons. Furthermore, we identify cell 29 type-specific pathways involving endoplasmic reticulum-stress, circadian signaling, ion 30 channels, neuropeptides, and receptors. Combined with methods to validate and manipulate 31 these pathways, this resource greatly expands molecular insight into neuronal regulation of 32 body weight, and may be useful for devising therapeutic strategies for obesity and eating 33 disorders.
    [Show full text]
  • The Neural Chaperone Prosaas Blocks Α-Synuclein Fibrillation and Neurotoxicity
    The neural chaperone proSAAS blocks α-synuclein fibrillation and neurotoxicity Timothy S. Jarvelaa, Hoa A. Lamb, Michael Helwiga,1, Nikolai Lorenzenc,2, Daniel E. Otzenc, Pamela J. McLeand, Nigel T. Maidmentb, and Iris Lindberga,3 aSchool of Medicine, University of Maryland, Baltimore, MD 21201; bDepartment of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, CA 90024; cInterdisciplinary Nanoscience Centre (iNANO), Department of Molecular Biology and Genetics, Aarhus University, DK-8000 Aarhus C, Denmark; and dDepartment of Neuroscience, Mayo Clinic, Jacksonville, FL 32224 Edited by Solomon H. Snyder, The Johns Hopkins University School of Medicine, Baltimore, MD, and approved June 14, 2016 (received for review January 20, 2016) Emerging evidence strongly suggests that chaperone proteins are the proprotein convertase PC1/3 (23, 24), proSAAS distribution cytoprotective in neurodegenerative proteinopathies involving pro- within the brain is far wider than that of PC1/3 (20, 21). ProSAAS tein aggregation; for example, in the accumulation of aggregated and PC1/3 expression are also not coregulated (25, 26), supporting a α-synuclein into the Lewy bodies present in Parkinson’sdisease.Of broader array of neuronal functions for proSAAS beyond its in- the various chaperones known to be associated with neurodegener- teractionwithPC1/3. ative disease, the small secretory chaperone known as proSAAS Interestingly, the proSAAS protein has been increasingly asso- (named after four residues in the amino terminal region) has many ciated with the presence of neurodegenerative disease. Immuno- attractive properties. We show here that proSAAS, widely expressed reactive proSAAS has been identified in neurofibrillary tangles in neurons throughout the brain, is associated with aggregated syn- and plaques in brain tissue from patients with Alzheimer’sdisease, uclein deposits in the substantia nigra of patients with Parkinson’s Pick’s disease, and Parkinsonism–dementia complex (27, 28).
    [Show full text]
  • Carboxypeptidase E Cytoplasmic Tail Mediates Localization of Synaptic
    JOURNAL OF NEUROCHEMISTRY | 2010 | 114 | 886–896 doi: 10.1111/j.1471-4159.2010.06820.x ,1 , ,1 *Section on Cellular Neurobiology, Program on Developmental Neuroscience, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA Department of Neurosciences, University of Toledo, School of Medicine, Toledo, Ohio, USA àDepartment of Pharmacology, University of Michigan, School of Medicine, Ann Arbor, Michigan, USA Abstract tion. Yeast two-hybrid and pull-down experiments showed that How synaptic vesicles (SVs) are localized to the pre-active the CPE cytoplasmic tail interacted with c-adducin, which zone (5–200 nm beneath the active zone) in the nerve ter- binds actin enriched at the nerve terminal. Total internal minal, which may represent the slow response SV pool, is not reflective fluorescence (TIRF) microscopy using PC12 cells as fully understood. Electron microscopy revealed the number of a model showed that expression of GFP-CPEC15 reduced the SVs located in the pre-active zone, was significantly de- steady-state level of synaptophysin-mRFP containing synap- creased in hypothalamic neurons of carboxypeptidase E tic-like microvesicles accumulated in the area within 200 nm knockout (CPE-KO) mice compared with wild-type mice. from the sub-plasma membrane (TIRF zone). Our findings Additionally, we found K+-stimulated glutamate secretion from identify the CPE cytoplasmic tail, as a new mediator for the hypothalamic embryonic neurons was impaired in CPE-KO localization of SVs in the actin-rich pre-active zone in hypo- mice. Biochemical studies indicate that SVs from the hypo- thalamic neurons and the TIRF zone of PC12 cells.
    [Show full text]
  • The VGF-Derived Peptide TLQP-62 Modulates Insulin Secretion and Glucose Homeostasis
    P PETROCCHI-PASSERI and others Action of VGF peptides on 54:3 227–239 Research insulinoma cells The VGF-derived peptide TLQP-62 modulates insulin secretion and glucose homeostasis Pamela Petrocchi-Passeri1,2, Cheryl Cero3, Alessandro Cutarelli1,4, Claudio Frank4, Cinzia Severini2,5, Alessandro Bartolomucci3 and Roberta Possenti1,2 1Department of Medicine of Systems, University of Rome Tor Vergata, Via Montpellier, 100133 Rome, Italy Correspondence 2Institute of Cell Biology and Neurobiology, CNR, Rome, Italy should be addressed 3Department of Integrative Biology and Physiology, University of Minnesota, Minneapolis, Minnesota, USA to R Possenti 4Istituto Superiore di Sanita` , Rome, Italy Email 5EBRI Foundation, Rome, Italy [email protected] Abstract Insulin secretion control is critical for glucose homeostasis. Paracrine and autocrine Key Words molecules secreted by cells of the islet of Langerhans, as well as by intramural and autonomic " neuropeptide neurons, control the release of different hormones that modulate insulin secretion. " intracellular calcium In pancreatic islets, the abundant presence of the granin protein VGF (nonacronymic; " signaling unrelated to VEGF) suggests that some of its proteolytically derived peptides could modulate " GSIS hormone release. Thus, in the present study, we screened several VGF-derived peptides for " diabetes their ability to induce insulin secretion, and we identified the VGF C-terminal peptide TLQP- 62 as the most effective fragment. TLQP-62 induced a potent increase in basal insulin secretion as well as in glucose-stimulated insulin secretion in several insulinoma cell lines. We Journal of Molecular Endocrinology found that this peptide stimulated insulin release via increased intracellular calcium mobilization and fast expression of the insulin 1 gene.
    [Show full text]
  • For Parkinson's Disease with Cognitive Impairment
    bioRxiv preprint doi: https://doi.org/10.1101/2021.03.19.436097; this version posted March 19, 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. Fibrinogen and Complement Factor H are promising CSF protein biomarker(s) for Parkinson’s disease with cognitive impairment- A Proteomics and ELISA based study Aditi Naskar1a, Albert Stezin2a, Arpitha Dharmappa3a, Shantala Hegde3a, Mariamma Philip4a, Nitish Kamble6a, Jitender Saini5a, Ravi Yadav6a, Sandhya K7b, Utpal Tatu8c, Pramod Kumar Pal6a#, Phalguni Anand Alladi1a* 1. Department of Clinical Psychopharmacology & Neurotoxicology 2. Department of Clinical Neurosciences 3. Department of Clinical Psychology 4. Department of Biostatistics 5. Department of Neuroimaging & Interventional Radiology 6. Department of Neurology 7. Department of Anaesthesiology 8. Department of Biochemistry a. National Institute of Mental Health and Neuro Sciences, Bengaluru, India b. Bangalore Medical College and Research Institute, Bengaluru, India c. Indian Institute of Science, Bengaluru, India *Corresponding Author: # Joint Corresponding Author Dr. Phalguni Anand Alladi Dr. Pramod Kumar Pal Senior Scientific Officer- Scientist ‘F’ Professor, Department of Neurology, Department of Clinical Psychopharmacology NIMHANS Parkinson's Disease & Movement and Neurotoxicology Disorders Subspeciality, National Institute of Mental Health & Neuro National Institute of Mental Health & Neuro Sciences, Hosur Road Bengaluru, 560029, Sciences, Hosur Road Bengaluru, 560029, Karnataka, INDIA Karnataka, INDIA Email: [email protected] [email protected] bioRxiv preprint doi: https://doi.org/10.1101/2021.03.19.436097; this version posted March 19, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder.
    [Show full text]