Hypoxia Restrains the Expression of Complement Component 9 in Tumor
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ESID Registry – Working Definitions for Clinical Diagnosis of PID
ESID Registry – Working Definitions for Clinical Diagnosis of PID These criteria are only for patients with no genetic diagnosis*. *Exceptions: Atypical SCID, DiGeorge syndrome – a known genetic defect and confirmation of criteria is mandatory. Available entries (Please click on an entry to see the criteria.) Page Acquired angioedema .................................................................................................................................................................. 4 Agammaglobulinemia .................................................................................................................................................................. 4 Asplenia syndrome (Ivemark syndrome) ................................................................................................................................... 4 Ataxia telangiectasia (ATM) ......................................................................................................................................................... 4 Atypical Severe Combined Immunodeficiency (Atypical SCID) ............................................................................................... 5 Autoimmune lymphoproliferative syndrome (ALPS) ................................................................................................................ 5 APECED / APS1 with CMC - Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED) .................. 5 Barth syndrome ........................................................................................................................................................................... -
Comprehensive Genetic Analysis of Complement and Coagulation Genes in Atypical Hemolytic Uremic Syndrome
BASIC RESEARCH www.jasn.org Comprehensive Genetic Analysis of Complement and Coagulation Genes in Atypical Hemolytic Uremic Syndrome † † † ‡ † Fengxiao Bu,* Tara Maga,* Nicole C. Meyer, Kai Wang, Christie P. Thomas, § † † Carla M. Nester, § and Richard J. H. Smith* § *Interdisciplinary PhD Program in Genetics, †Molecular Otolaryngology and Renal Research Laboratories, ‡Department of Biostatistics, College of Public Health, and §Rare Renal Disease Clinic, Departments of Pediatrics and Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, Iowa ABSTRACT Atypical hemolytic uremic syndrome (aHUS) is a thrombotic microangiopathy caused by uncontrolled activation of the alternative pathway of complement at the cell surface level that leads to microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney failure. In approximately one half of affected patients, pathogenic loss-of-function variants in regulators of complement or gain-of-function variants in effectors of complement are identified, clearly implicating complement in aHUS. However, there are strong lines of evidence supporting the presence of additional genetic contributions to this disease. To identify novel aHUS-associated genes, we completed a comprehensive screen of the complement and coagulation pathways in 36 patients with sporadic aHUS using targeted genomic enrichment and mas- sively parallel sequencing. After variant calling, quality control, and hard filtering, we identified 84 reported or novel nonsynonymous variants, 22 of which have been previously associated with disease. Using computational prediction methods, 20 of the remaining 62 variants were predicted to be dele- terious. Consistent with published data, nearly one half of these 42 variants (19; 45%) were found in genes implicated in the pathogenesis of aHUS. Several genes in the coagulation pathway were also identified as important in the pathogenesis of aHUS. -
The Effect of Bee Venom Peptides Melittin, Tertiapin, and Apamin On
H OH metabolites OH Article The Effect of Bee Venom Peptides Melittin, Tertiapin, and Apamin on the Human Erythrocytes Ghosts: A Preliminary Study 1, 2, 1 3 Agata Swiatły-Błaszkiewicz´ y, Lucyna Mrówczy ´nska y, Eliza Matuszewska , Jan Lubawy , Arkadiusz Urba ´nski 3 , Zenon J. Kokot 1, Grzegorz Rosi ´nski 3 and Jan Matysiak 1,* 1 Department of Inorganic and Analytical Chemistry, Poznan University of Medical Sciences, 60-780 Poznan, Poland; [email protected] (A.S.-B.);´ [email protected] (E.M.); [email protected] (Z.J.K.) 2 Department of Cell Biology, Faculty of Biology, Adam Mickiewicz University in Poznan, 61-614 Poznan, Poland; [email protected] 3 Department of Animal Physiology and Development, Faculty of Biology, Adam Mickiewicz University in Poznan, 61-614 Poznan, Poland; [email protected] (J.L.); [email protected] (A.U.); [email protected] (G.R.) * Correspondence: [email protected] These two authors contributed equally to this work. y Received: 11 April 2020; Accepted: 11 May 2020; Published: 13 May 2020 Abstract: Red blood cells (RBCs) are the most abundant cells in the human blood that have been extensively studied under morphology, ultrastructure, biochemical and molecular functions. Therefore, RBCs are excellent cell models in the study of biologically active compounds like drugs and toxins on the structure and function of the cell membrane. The aim of the present study was to explore erythrocyte ghost’s proteome to identify changes occurring under the influence of three bee venom peptides-melittin, tertiapin, and apamin. We conducted preliminary experiments on the erythrocyte ghosts incubated with these peptides at their non-hemolytic concentrations. -
Aberrant Complement System Activation in Neurological Disorders
International Journal of Molecular Sciences Review Aberrant Complement System Activation in Neurological Disorders Karolina Ziabska , Malgorzata Ziemka-Nalecz, Paulina Pawelec, Joanna Sypecka and Teresa Zalewska * Mossakowski Medical Research Centre, NeuroRepair Department, Polish Academy of Sciences, 5 Pawinskiego Street, 02-106 Warsaw, Poland; [email protected] (K.Z.); [email protected] (M.Z.-N.); [email protected] (P.P.); [email protected] (J.S.) * Correspondence: [email protected]; Tel.: +48-(22)-608-65-29; Fax: +48-(22)-608-66-23 Abstract: The complement system is an assembly of proteins that collectively participate in the functions of the healthy and diseased brain. The complement system plays an important role in the maintenance of uninjured (healthy) brain homeostasis, contributing to the clearance of invading pathogens and apoptotic cells, and limiting the inflammatory immune response. However, overacti- vation or underregulation of the entire complement cascade within the brain may lead to neuronal damage and disturbances in brain function. During the last decade, there has been a growing interest in the role that this cascading pathway plays in the neuropathology of a diverse array of brain disorders (e.g., acute neurotraumatic insult, chronic neurodegenerative diseases, and psychiatric disturbances) in which interruption of neuronal homeostasis triggers complement activation. Dys- function of the complement promotes a disease-specific response that may have either beneficial or detrimental effects. Despite recent advances, the explicit link between complement component regulation and brain disorders remains unclear. Therefore, a comprehensible understanding of such relationships at different stages of diseases could provide new insight into potential therapeutic targets to ameliorate or slow progression of currently intractable disorders in the nervous system. -
Target Deletion of Complement Component 9
www.nature.com/scientificreports OPEN Target deletion of complement component 9 attenuates antibody-mediated hemolysis and Received: 08 March 2016 Accepted: 01 July 2016 lipopolysaccharide (LPS)-induced Published: 22 July 2016 acute shock in mice Xiaoyan Fu1,*, Jiyu Ju1,*, Zhijuan Lin1, Weiling Xiao1, Xiaofang Li1, Baoxiang Zhuang1, Tingting Zhang1, Xiaojun Ma1, Xiangyu Li1, Chao Ma1, Weiliang Su1, Yuqi Wang1, Xuebin Qin2 & Shujuan Liang1 Terminal complement membrane attack complex (MAC) formation is induced initially by C5b, followed by the sequential condensation of the C6, C7, C8. Polymerization of C9 to the C5b-8 complex forms the C5b-9 (or MAC). The C5b-9 forms lytic or non lytic pores in the cell membrane destroys membrane integrity. The biological functionalities of MAC has been previously investigated by using either the mice deficient in C5 and C6, or MAC’s regulator CD59. However, there is no available C9 deficient mice (mC9−/−) for directly dissecting the role of C5b-9 in the pathogenesis of human diseases. Further, since C5b-7 and C5b-8 complexes form non lytic pore, it may also plays biological functionality. To better understand the role of terminal complement cascades, here we report a successful generation of mC9−/−. We demonstrated that lack of C9 attenuates anti-erythrocyte antibody-mediated hemolysis or LPS-induced acute shock. Further, the rescuing effect on the acute shock correlates with the less release of IL-1β in mC9−/−, which is associated with suppression of MAC-mediated inflammasome activation in mC9−/−. Taken together, these results not only confirm the critical role of C5b-9 in complement- mediated hemolysis and but also highlight the critical role of C5b-9 in inflammasome activation. -
Deficiency of Complement Defense Protein CD59 May Contribute To
The Journal of Neuroscience, October 15, 2000, 20(20):7505–7509 Deficiency of Complement Defense Protein CD59 May Contribute to Neurodegeneration in Alzheimer’s Disease Li-Bang Yang,1 Rena Li,1 Seppo Meri,2 Joseph Rogers,1 and Yong Shen1 1L. J. Roberts Center for Alzheimer’s Research, Sun Health Research Institute, Sun City, Arizona 85351, and 2Department of Immunology, Haartman Institute, University of Helsinki, Finland Complement defense 59 (CD59) is a cell surface glycophos- To evaluate the pathophysiological significance of CD59 alter- phoinositol (GPI)-anchored protein that prevents complement ations in neurons, we exposed cultured NT2 cells, which normally membrane attack complex (MAC) assembly. Here, we present underexpress CD59, and NT2 cells transfected to overexpress evidence from ELISA assays that CD59 protein levels are signif- CD59 to homologous human serum. Lactic acid dehydrogenase icantly decreased in the frontal cortex and hippocampus of assays revealed significant complement-induced cell lysis in CD59- Alzheimer’s disease (AD) compared with nondemented elderly underexpressing NT2 cells and significant protection from such (ND) patients, whereas complement component 9, a final com- lysis in CD59-overexpressing NT2 cells. Moreover, cells expressing ponent to form MAC, is significantly increased. To further confirm normal levels of CD59 showed no evidence of MAC assembly or the CD59 deficit, PI-specific phospholipase C (PIPLC) was used damage after exposure to homologous serum, whereas pretreat- to cleave the CD59 GPI anchor at the cell surface in intact slices ment of these cells with a CD59-neutralizing antibody resulted in from AD and ND cortex. CD59 released by PIPLC cleavage was MAC assembly at the cell surface and morphological damage. -
A Computational Model for the Evaluation of Complement System Regulation Under Homeostasis, Disease, and Drug Intervention
bioRxiv preprint doi: https://doi.org/10.1101/225029; this version posted November 25, 2017. 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. A Computational Model for the Evaluation of Complement System Regulation under Homeostasis, Disease, and Drug Intervention Nehemiah Zewde and Dimitrios Morikis* Department of Bioengineering University of California, Riverside *Corresponding author. E-mail address: [email protected] (D. Morikis) Key words: Computational ODE model; immune system regulation; complement system pathways; disease model; Factor H; compstatin; eculizumab. Page 1 of 33 bioRxiv preprint doi: https://doi.org/10.1101/225029; this version posted November 25, 2017. 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. Highlights • Computational model describing dynamics of complement system activation pathways • Complement dysregulation leads to deviation from homeostasis and to inflammatory diseases • Model identifies biomarkers to quantify the effects of complement dysregulation • Known drugs restore impaired dynamics of complement biomarkers under dysregulation • Disease-specific models are suitable for diagnosis and patient-specific drug treatment Page 2 of 33 bioRxiv preprint doi: https://doi.org/10.1101/225029; this version posted November 25, 2017. 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. Abstract The complement system is a part of innate immunity that rapidly removes invading pathogens and impaired host-cells. Activation of the complement system is balanced under homeostasis by regulators that protect healthy host-cells. -
Single-Molecule Kinetics of Pore Assembly by the Membrane Attack Complex
bioRxiv preprint doi: https://doi.org/10.1101/472274; this version posted November 16, 2018. 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. Single-molecule kinetics of pore assembly by the membrane attack complex Edward S. Parsons1,*, George J. Stanley1, Alice L. B. Pyne1, Adrian W. Hodel1,2, Adrian P. Nievergelt3, Anaïs Menny4, Alexander R. Yon1,2, Ashlea Rowley5, Ralf P. Richter5,6,7, Georg E. Fantner3, Doryen Bubeck4, and Bart W. Hoogenboom1,2,8,* 1 London Centre for Nanotechnology, University College London, London WC1H 0AH, United Kingdom. 2 Institute of Structural and Molecular Biology, University College London, London WC1E 6BT, United Kingdom. 3 Laboratory for Bio- and Nano-Instrumentation, Swiss Federal Institute of Technology Lausanne (EPFL), 1015 Lausanne, Switzerland. 4 Department of Life Sciences, Imperial College London, South Kensington Campus, London SW7 2AZ, United Kingdom. 5 School of Biomedical Sciences, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, United Kingdom. 6 School of Physics and Astronomy, Faculty of Mathematics and Physical Sciences, University of Leeds, Leeds LS2 9JT, United Kingdom. 7 Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds LS2 9JT, United Kingdom. 8 Department of Physics and Astronomy, University College London, London WC1E 6BT, United Kingdom * Email: [email protected], [email protected] 1 bioRxiv preprint doi: https://doi.org/10.1101/472274; this version posted November 16, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. -
The Role of Complement System and the Immune Response to Tuberculosis Infection
medicina Review The Role of Complement System and the Immune Response to Tuberculosis Infection Heena Jagatia 1,* and Anthony G. Tsolaki 2 1 Department for Respiratory Sciences, University of Leicester, Leicester LE1 9HN, UK 2 Department of Life Sciences, College of Health and Life Sciences, Brunel University of London, Uxbridge UB8 3PN, UK; [email protected] * Correspondence: [email protected] Abstract: The complement system orchestrates a multi-faceted immune response to the invading pathogen, Mycobacterium tuberculosis. Macrophages engulf the mycobacterial bacilli through bacterial cell surface proteins or secrete proteins, which activate the complement pathway. The classical pathway is activated by C1q, which binds to antibody antigen complexes. While the alternative pathway is constitutively active and regulated by properdin, the direct interaction of properdin is capable of complement activation. The lectin-binding pathway is activated in response to bacterial cell surface carbohydrates such as mannose, fucose, and N-acetyl-D-glucosamine. All three pathways contribute to mounting an immune response for the clearance of mycobacteria. However, the bacilli can reside, persist, and evade clearance by the immune system once inside the macrophages using a number of mechanisms. The immune system can compartmentalise the infection into a granulomatous structure, which contains heterogenous sub-populations of M. tuberculosis. The granuloma consists of many types of immune cells, which aim to clear and contain the infection whilst sacrificing the affected host tissue. The full extent of the involvement of the complement system during infection with M. tuberculosis is not fully understood. Therefore, we reviewed the available literature on M. tuberculosis and other mycobacterial literature to understand the contribution of the Citation: Jagatia, H.; Tsolaki, A.G. -
(MDR/TAP), Member 1 ABL1 NM 00
Official Symbol Accession Official Full Name ABCB1 NM_000927.3 ATP-binding cassette, sub-family B (MDR/TAP), member 1 ABL1 NM_005157.3 c-abl oncogene 1, non-receptor tyrosine kinase ADA NM_000022.2 adenosine deaminase AHR NM_001621.3 aryl hydrocarbon receptor AICDA NM_020661.1 activation-induced cytidine deaminase AIRE NM_000383.2 autoimmune regulator APP NM_000484.3 amyloid beta (A4) precursor protein ARG1 NM_000045.2 arginase, liver ARG2 NM_001172.3 arginase, type II ARHGDIB NM_001175.4 Rho GDP dissociation inhibitor (GDI) beta ATG10 NM_001131028.1 ATG10 autophagy related 10 homolog (S. cerevisiae) ATG12 NM_004707.2 ATG12 autophagy related 12 homolog (S. cerevisiae) ATG16L1 NM_198890.2 ATG16 autophagy related 16-like 1 (S. cerevisiae) ATG5 NM_004849.2 ATG5 autophagy related 5 homolog (S. cerevisiae) ATG7 NM_001136031.2 ATG7 autophagy related 7 homolog (S. cerevisiae) ATM NM_000051.3 ataxia telangiectasia mutated B2M NM_004048.2 beta-2-microglobulin B3GAT1 NM_018644.3 beta-1,3-glucuronyltransferase 1 (glucuronosyltransferase P) BATF NM_006399.3 basic leucine zipper transcription factor, ATF-like BATF3 NM_018664.2 basic leucine zipper transcription factor, ATF-like 3 BAX NM_138761.3 BCL2-associated X protein BCAP31 NM_005745.7 B-cell receptor-associated protein 31 BCL10 NM_003921.2 B-cell CLL/lymphoma 10 BCL2 NM_000657.2 B-cell CLL/lymphoma 2 BCL2L11 NM_138621.4 BCL2-like 11 (apoptosis facilitator) BCL3 NM_005178.2 B-cell CLL/lymphoma 3 BCL6 NM_001706.2 B-cell CLL/lymphoma 6 BID NM_001196.2 BH3 interacting domain death agonist BLNK NM_013314.2 -
Exploring the Cross Talk Between ER Stress and Inflammation in Age-Related Macular Degeneration
RESEARCH ARTICLE Exploring the cross talk between ER stress and inflammation in age-related macular degeneration Samira Kheitan1, Zarrin Minuchehr1*, Zahra-Soheila Soheili2 1 Systems Biotechnology Department, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran, 2 Molecular Medicine Department, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran a1111111111 * [email protected] a1111111111 a1111111111 a1111111111 Abstract a1111111111 Increasing evidence demonstrates that inflammation and endoplasmic reticulum (ER) stress is implicated in the development and progression of age-related macular degeneration (AMD), a multifactorial neurodegenerative disease. However the cross talk between these OPEN ACCESS cellular mechanisms has not been clearly and fully understood. The present study investi- gates a possible intersection between ER stress and inflammation in AMD. In this study, we Citation: Kheitan S, Minuchehr Z, Soheili Z-S (2017) Exploring the cross talk between ER stress recruited two collections of involved protein markers to retrieve their interaction information and inflammation in age-related macular from IMEx-curated databases, which are the most well- known protein-protein interaction degeneration. PLoS ONE 12(7): e0181667. https:// collections, allowing us to design an intersection network for AMD that is unprecedented. In doi.org/10.1371/journal.pone.0181667 order to find expression activated subnetworks, we utilized AMD expression profiles in our Editor: Rui Kang, University of Pittsburgh, UNITED network. In addition, we studied topological characteristics of the most expressed active STATES subnetworks to identify the hubs. With regard to topological quantifications and expressional Received: April 18, 2017 activity, we reported a list of the most pivotal hubs which are potentially applicable as pro- Accepted: July 5, 2017 bable therapeutic targets. -
Proteomic Landscape of the Human Choroid–Retinal Pigment Epithelial Complex
Supplementary Online Content Skeie JM, Mahajan VB. Proteomic landscape of the human choroid–retinal pigment epithelial complex. JAMA Ophthalmol. Published online July 24, 2014. doi:10.1001/jamaophthalmol.2014.2065. eFigure 1. Choroid–retinal pigment epithelial (RPE) proteomic analysis pipeline. eFigure 2. Gene ontology (GO) distributions and pathway analysis of human choroid– retinal pigment epithelial (RPE) protein show tissue similarity. eMethods. Tissue collection, mass spectrometry, and analysis. eTable 1. Complete table of proteins identified in the human choroid‐RPE using LC‐ MS/MS. eTable 2. Top 50 signaling pathways in the human choroid‐RPE using MetaCore. eTable 3. Top 50 differentially expressed signaling pathways in the human choroid‐RPE using MetaCore. eTable 4. Differentially expressed proteins in the fovea, macula, and periphery of the human choroid‐RPE. eTable 5. Differentially expressed transcription proteins were identified in foveal, macular, and peripheral choroid‐RPE (p<0.05). eTable 6. Complement proteins identified in the human choroid‐RPE. eTable 7. Proteins associated with age related macular degeneration (AMD). This supplementary material has been provided by the authors to give readers additional information about their work. © 2014 American Medical Association. All rights reserved. 1 Downloaded From: https://jamanetwork.com/ on 09/25/2021 eFigure 1. Choroid–retinal pigment epithelial (RPE) proteomic analysis pipeline. A. The human choroid‐RPE was dissected into fovea, macula, and periphery samples. B. Fractions of proteins were isolated and digested. C. The peptide fragments were analyzed using multi‐dimensional LC‐MS/MS. D. X!Hunter, X!!Tandem, and OMSSA were used for peptide fragment identification. E. Proteins were further analyzed using bioinformatics.