Oxidized S100A4 Inhibits the Activation of Protein Phosphatase 5 Through S100A1 in MKN‑45 Gastric Carcinoma Cells

Total Page:16

File Type:pdf, Size:1020Kb

Oxidized S100A4 Inhibits the Activation of Protein Phosphatase 5 Through S100A1 in MKN‑45 Gastric Carcinoma Cells INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE 34: 1713-1719, 2014 Oxidized S100A4 inhibits the activation of protein phosphatase 5 through S100A1 in MKN‑45 gastric carcinoma cells MITSUMASA TSUCHIYA1*, FUMINORI YAMAGUCHI2*, SEIKO SHIMAMOTO1, TOMOHITO FUJIMOTO1, HIROSHI TOKUMITSU1, MASAAKI TOKUDA2 and RYOJI KOBAYASHI1 Departments of 1Signal Transduction Sciences and 2Cell Physiology, Kagawa University Faculty of Medicine, Kagawa 761‑0793, Japan Received March 8, 2014; Accepted September 23, 2014 DOI: 10.3892/ijmm.2014.1947 Abstract. S100 proteins bind to numerous target proteins, as Introduction well as other S100 proteins and activate signaling cascades. S100 proteins can be modified by various post‑translational S100A4 protein is a member of the EF-hand calcium modifications, such as phosphorylation, methylation and acety- ion‑binding protein family, of which >25 members have lation. In addition, oxidation is important for modulating their been found in humans (1). They are 25‑65% homologous at activities. Previous studies have shown that S100A1 interacts the amino acid level, while the sequence of the linker (hinge) with S100A4 in vitro and in vivo. Due to this potential cross-talk region and the C-terminal extension are the most variable among the S100 proteins, the aim of the present study was to among the S100 proteins. Each S100 monomer contains two examine whether S100A4 modulates the activity of S100A1. EF-hand Ca2+-binding sites. Ca2+-binding causes a conforma- S100A4 was readily oxidized and formed disulfide‑linked tional change and exposure of a hydrophobic surface allowing dimers and oligomers. Although non‑oxidized S100A4 bound interaction with target proteins (2). They do not possess to protein phosphatase 5 (PP5), the Cu‑oxidized S100A4 failed enzymatic activity, but rather regulate the activity of target to bind PP5. Instead, the Cu‑oxidized S100A4 directly inter- proteins. Several proteins have been identified as S100A4 acted with S100A1 and prevented PP5 activation. Hydrogen targets, including liprin β1 (3), methionine aminopeptidase (4), peroxide induced S100A4 oxidation in MKN-45 gastric the p53 tumor suppressor protein (5) and the heavy chain of adenocarcinoma cells and decreased S100A1-PP5 interaction, non‑muscle myosin II (6). In addition, S100A4 is capable of resulted in the inhibition of PP5 activation by S100A1. These forming heterodimers with S100A1 (7,8), which is likely to data indicate that oxidized S100A4 regulates PP5 activity in a increase its functional potential. Previous studies have shown unique manner under oxidative stress conditions. that S100A4 interacts with S100A1 via heterodimer formation and that S100A1 can antagonize function of S100A4 (9,10). It has been a general observation that two‑hybrid screenings utilizing S100 proteins have primarily detected other S100 family members as targets (11‑13). Correspondence to: Professor Ryoji Kobayashi, Department We have previously demonstrated that S100A1, A2, A6 of Signal Transduction Sciences, Kagawa University Faculty of and S100B interact with the tetratricopeptide repeat (TPR) Medicine, 1750‑1 Ikenobe, Kagawa 761‑0793, Japan 2+ E‑mail: [email protected]‑u.ac.jp domain of PP5 in a Ca ‑dependent manner and significantly activate its phosphatase activity (14). PP5 is a member of the *Contributed equally phosphoprotein phosphatase (PPP) family of a serine/threo- nine phosphatase (15). PP5 contains a C‑terminal catalytic Abbreviations: ASK1, apoptosis stimulating kinase 1; CaM, domain and N-terminal three TPR motifs that are unique in calmodulin; CBB, Coomassie brilliant blue; DTT, dithiothreitol; the PPP family (16,17). The TPR motif consists of 34 amino H2O2, hydrogen peroxide; HMW, higher molecular weight; His, acid sequences, and between 3 and 16 copies of the motif are 6xHistidine; HRP, horseradish peroxidase; NF‑κB, nuclear factor-κB; arranged in the proteins as tandem arrays (18,19). This motif PBS, phosphate-buffered saline; PP5, protein phosphatase 5; PPP, can act as an interaction scaffold for protein complex forma- phosphoprotein phosphatase; ROS, reactive oxygen species; SPR, tion. PP5 is a negative regulator of the apoptosis stimulating surface plasmon resonance; TNF-α, tumor necrosis factor α; TPR, tetratricopeptide repeat; Tricine, N‑[2‑hydroxy‑1,1‑bis (hydroxymethyl) kinase 1 (ASK1) and modulates the apoptosis under oxidative ethyl] glycine; TTBS, Tris‑buffered saline with 0.05% Tween‑20 stress conditions (20). Gastric epithelium is constantly exposed to reactive oxygen species (ROS) and activation of ASK1 by Key words: oxidative stress, S100 protein, protein phosphatase 5, Helicobacter pylori under oxidative stress was reported previ- MKN-45 ously (21). The purpose of the present study was to investigate whether S100A4 affects S100A1 function (i.e., PP5 activation) under oxidative conditions. The oxidized form of S100A4, but not 1714 TSUCHIYA et al: INHIBITION OF S100A1-PP5 INTERACTION AND PP5 ACTIVATION BY OXIDIZED S100A4 the native S100A4 dimer, was found to inhibit the activation of treated with or without 2 mM H2O2 and 0.5 µM ionomycin for PP5 by S100A1 in vitro and in MKN-45 cells. 90 min. Cells were washed once with PBS and lysed in a buffer consisting of 50 mM Tris‑HCl (pH 7.5), 150 mM NaCl, 0.5% Materials and methods Triton X‑100, and 0.5% Nonidet P‑40 with protease inhibitor mixture (Roche). The samples were sonicated and centrifuged Materials. Nickel-nitrilotriacetic acid-agarose was purchased at 16,600 x g for 10 min. Supernatants were incubated with from Qiagen (Hilden, Germany). Rabbit anti-S100A1 anti- 30 µl of anti‑FLAG antibody‑agarose in the presence of body (NB100‑91955) was obtained from Novus Biologicals 1 mM CaCl2 for 2 h at room temperature. Following extensive (Littleton, CO, USA). Sheep anti‑S100A4 antibody (AF4138) washing, the beads were used either for the western blotting or was obtained from R&D Systems (Minneapolis, MN, USA). in vitro phosphatase assay. Mouse anti-FLAG-horseradish peroxidase (HRP) antibody (A8592) and other chemicals were purchased from Sigma Surface plasmon resonance (SPR). Protein binding (St. Louis, MO, USA). Goat-anti-rabbit IgG- HRP-linked anti- analysis was performed using an SPR Biacore 2000 body (7074) was obtained from Cell Signaling (Beverly, MA, system (GE Healthcare Institute, Waukesha, WI, USA). USA) and Donkey‑anti‑sheep IgG‑HRP‑conjugated antibody N‑ethyl‑N'‑(3‑diethylaminopropyl) carbodiimide, (HAF016) was purchased from R&D Systems. N‑hydroxysuccinimide and ethanolamine‑HCl (GE Healthcare) were used for amine coupling of PP5 or S100A1 Plasmids and recombinant proteins. Human PP5 [GenBank: to the dextran surface of the CM5 chip. His-PP5 [2500 RU NM_006247] was cloned to pET16a and pME18S‑FLAG (pH 4.2)] or S100A1 [1400 RU (pH 4.5)] were immobilized vector, and rat S100A1 [Genbank: NM_001007636] and rat in 10-mM ammonium acetate. For all the procedures, HBS-P S100A4 [Genbank: NM_012618] were cloned to pET11a buffer [20 mM HEPES (pH 7.4), 150 mM NaCl and 0.005% plasmids as previously reported (14). Histidine‑tagged PP5 Tween‑20] with 1 mM CaCl2 were used at a flow rate of (His‑PP5) protein was expressed and purified according to the 20 µl/min. Various concentrations of recombinant S100 manufacturer's instructions. S100A1 and S100A4 proteins were proteins were injected. The ligand-coupled sensor chips were expressed and purified as previously described (22,23). Purified regenerated between protein injections with a brief (60 sec) recombinant S100A4 proteins were diluted (0.5 mg/ml) and wash with HBS‑P buffer containing 2.5 mM ethyleneglycol‑ maintained at -30˚C in a freezer for 3 months (air‑oxidized). bis‑(2‑aminoethylether)‑tetra acetic acid (EGTA) and 0.75% Cu‑oxidized S100A4 protein was prepared in accordance with n‑octyl‑β‑D‑glucopyranoside. Response curves were prepared a previous study (24). Briefly, S100A4 (10 µM) was incubated for fitting by subtraction of the signal generated simultane- with 80 µM of CuCl2 in 20 mM Tris‑HCl buffer (pH 7.6) for 2 h ously on the control flow cell. Biacore sensorgrams were at 37˚C. Subsequent to stopping the reaction with the copper analyzed using BIAevaluation 4.1 software (GE Healthcare). chelator diethylenetriamine‑N,N,N',N',N'-pentaacetic acid, the product solution was desalted using centriprep-3 (Amicon, Inc., Native PAGE, Tricine SDS‑PAGE and western blotting. Native Beverly, MA, USA), dialyzed against 20 mM Tris‑HCl buffer PAGE analysis was performed based on a previous study (25). (pH 7.6). For Tricine SDS‑PAGE analysis, samples were treated Tricine SDS-PAGE gel electrophoresis was performed under with (reducing conditions) or without (non-reducing conditions) reducing and non-reducing conditions. The gels were either 10 mM dithiothreitol (DTT) prior to electrophoresis. stained with Coomassie Brilliant Blue (CBB) or used for western blotting. For western blot analysis, proteins were blotted Cell culture and H2O2 treatment. MKN-45 cells were purchased onto nitrocellulose membranes and blocked with 5% skimmed from the Japanese Collection of Research Bioresources (Osaka, milk in Tris‑buffered saline with 0.05% Tween‑20 (TTBS). The Japan) and maintained in RPMI‑1640 (Sigma) supplemented membranes were incubated with an anti‑S100 antibody in the with 10% fetal bovine serum and 1% penicillin and strepto- same buffer overnight. Membranes were washed with TTBS mycin in a humidified 5% CO2 incubator. For the oxidative and incubated with an HRP‑labeled second antibody for 2 h. To stress experiment, 5.5x105 cells were plated on a 10-cm dish detect the FLAG‑tagged PP5, the anti‑FLAG‑HRP antibody and cultured for 3 days in standard medium. Medium was was used. The samples were washed and signals were detected aspirated and washed with phosphate-buffered saline (PBS) using Immobilon Western Chemiluminescent HRP Substrate and cells were exposed to the indicated concentrations of H2O2 (Millipore, Billerica, MA, USA). ranging from 0 to 2 mM in the serum-free medium for 90 min. Following exposure to oxidative stress, these cells were washed In vitro phosphatase assay.
Recommended publications
  • Unnatural Verticilide Enantiomer Inhibits Type 2 Ryanodine Receptor-Mediated Calcium Leak and Is Antiarrhythmic
    Unnatural verticilide enantiomer inhibits type 2 ryanodine receptor-mediated calcium leak and is antiarrhythmic Suzanne M. Batistea,1, Daniel J. Blackwellb,1, Kyungsoo Kimb,1, Dmytro O. Kryshtalb, Nieves Gomez-Hurtadob, Robyn T. Rebbeckc, Razvan L. Corneac, Jeffrey N. Johnstona,2, and Bjorn C. Knollmannb,2 aDepartment of Chemistry, Vanderbilt University, Nashville, TN 37235; bDepartment of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232; and cDepartment of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, MN 55455 Edited by Dale L. Boger, The Scripps Research Institute, La Jolla, CA, and approved January 15, 2019 (received for review September 27, 2018) Ca2+ leak via ryanodine receptor type 2 (RyR2) can cause poten- heart diseases associated with both atrial and ventricular arrhyth- tially fatal arrhythmias in a variety of heart diseases and has also mia (9). Mutations in RyR2 and its binding partners, which increase + been implicated in neurodegenerative and seizure disorders, mak- SR Ca2 leak, cause primary atrial and ventricular arrhythmia ing RyR2 an attractive therapeutic target for drug development. syndromes such as catecholaminergic polymorphic ventricular Here we synthesized and investigated the fungal natural product tachycardia (CPVT), providing strong evidence for the mechanistic and known insect RyR antagonist (−)-verticilide and several conge- contribution of RyR2 to arrhythmia risk in humans (10). Further ners to determine their activity against mammalian RyR2. Although support comes from gene-targeted mouse models of CPVT, where + the cyclooligomeric depsipeptide natural product (−)-verticilide had catecholamine-induced spontaneous Ca2 release from the SR no effect, its nonnatural enantiomer [ent-(+)-verticilide] signifi- via RyR2 generates potentially fatal cardiac arrhythmias (11, 12).
    [Show full text]
  • Association of Serum S100B, S100A1 and Zinc-Α2
    Progress in Nutrition 2019; Vol. 21, Supplement 1: 154-162 DOI: 10.23751/pn.v21i1-S.5846 © Mattioli 1885 Original articles Association of serum S100B, S100A1 and Zinc-α2- Glycoprotein levels with anthropometric, metabolic and clinical indices in men and women Sorayya Kheirouri1, Mohammad Alizadeh1, Elham Ebrahimi2, Masoumeh Jabbari2 1Associate Professor, Department of Nutrition, Tabriz University of Medical Sciences, Tabriz, Iran - Email: kheirouris@tbzmed. ac.ir, [email protected]; 2MSc. student, Department of Nutrition, Tabriz University of Medical Sciences, Tabriz, Iran Summary. Objectives: We aimed to investigate serum levels of S100B, S100A1, and Zinc-α2- glycoprotein (ZAG) in men and women and to find association of these proteins with anthropometric, metabolic and clini- cal indices. Methods: Eighty-eight apparently healthy adults, 43 men and 45 women, participated in the study. The participants’ body mass index (BMI), waist circumference (WC), systolic and diastolic blood pressure (SBP and DBP) were measured. Serum levels of total cholesterol (TC), triglyceride (TG), low and high den- sity lipoprotein cholesterol (LDL-C and HDL-C), fasting blood sugar (FBS), insulin, S100B, S100A1 and ZAG protein were examined by enzymatic and ELISA laboratory methods. Homeostatic model assessment- insulin resistance (HOMA-IR) index was calculated. Results: Serum levels of S100B, S100A1 and ZAG were comparable between men and women groups. S100B protein was positively associated with TG (r= 0.41, p= 0.006), SBP (r= 0.46, p= 0.002), and DBP (r= 0.37, p= 0.02), but negatively with HDL-c in men. Serum levels of S100A1 were significantly and negatively correlated with WC (r= -0.33, p= 0.03), TG (r= -0.37, p= 0.01), insulin (r= -0.31, p= 0.04) and HOMA-IR (r= -0.32, p= 0.03), in women.
    [Show full text]
  • Human S100A4 (P9ka) Induces the Metastatic Phenotype Upon Benign Tumour Cells
    Oncogene (1998) 17, 465 ± 473 1998 Stockton Press All rights reserved 0950 ± 9232/98 $12.00 http://www.stockton-press.co.uk/onc Human S100A4 (p9Ka) induces the metastatic phenotype upon benign tumour cells Bryony H Lloyd, Angela Platt-Higgins, Philip S Rudland and Roger Barraclough School of Biological Sciences, University of Liverpool, PO Box 147, Liverpool, L69 7ZB, UK The rodent S100-related calcium-binding protein, strengthened by the observation that transgenic mice, S100A4 induces metastasis in non-metastatic rat and expressing elevated levels of S100A4 (p9Ka) from 17 mouse benign mammary cells and co-operates with additional, position-independent rat S100A4 trans- benign-tumour-inducing changes in two transgenic mouse genes, fail to show any detectable phenotype (Davies, models, to yield metastatic mammary tumours. Co- 1993). When these mice are mated with transgenic mice transfection of the human gene for S100A4 with containing additional copies of the activated rodent c- pSV2neo into the benign rat mammary cell line, Rama erbB-2 oncogene, neu, under the control of the MMTV 37, yielded cells which expressed a low level of the LTR (Bouchard et al., 1989), ospring inheriting the endogenous S100A4 mRNA, and either high or neu oncogene suer sporadic mammary tumours after undetectable levels of human S100A4 mRNA. The cells 12 ± 14 months of repeated mating. In contrast which expressed a high level of human S100A4 mRNA ospring inheriting both neu and S100A4 transgenes induced metastasis in the benign rat mammary cell line show an elevated incidence of primary tumours, and, in Rama 37 in an in vivo assay, whereas the cells which addition, metastases in the lungs which account for up expressed an undetectable level of human S100A4 did to 24% of the total lung area (Davies et al., 1996).
    [Show full text]
  • Glial Protein S100B Modulates Long-Term Neuronal Synaptic Plasticity
    Glial protein S100B modulates long-term neuronal synaptic plasticity Hiroshi Nishiyama*†, Thomas Kno¨ pfel†, Shogo Endo‡, and Shigeyoshi Itohara*§ *Laboratories for Behavioral Genetics and †Neuronal Circuit Dynamics, and ‡Neuronal Circuit Mechanisms Research Group, Brain Science Institute (BSI), Institute of Physical and Chemical Research (RIKEN), 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan Communicated by Richard F. Thompson, University of Southern California, Los Angeles, CA, January 11, 2002 (received for review August 1, 2001) Glial cells are traditionally regarded as elements for structural subject of debate (1). Transgenic mice overexpressing human support and ionic homeostasis, but have recently attracted atten- S100B exhibit impaired hippocampal LTP and spatial learning tion as putative integral elements of the machinery involved in (11). Transgenic mice overexpressing S100B might not be ap- synaptic transmission and plasticity. Here, we demonstrate that propriate for evaluating the physiological roles of S100B, how- calcium-binding protein S100B, which is synthesized in consider- ever, because overexpression of S100B partly mimics patholog- able amounts in astrocytes (a major glial cell subtype), modulates ical conditions in some neuronal diseases, such as Down’s long-term synaptic plasticity. Mutant mice devoid of S100B devel- syndrome and Alzheimer’s disease (12, 13). The constitutive oped normally and had no detectable abnormalities in the cyto- overexpression of S100B might cause chronic neuronal damage architecture of the brain. These mutant mice, however, had (14, 15). Thus, there is no clear consensus regarding the signif- strengthened synaptic plasticity as identified by enhanced long- icance of this glial protein in neuronal synaptic plasticity. term potentiation (LTP) in the hippocampal CA1 region.
    [Show full text]
  • Absence of S100A4 in the Mouse Lens Induces an Aberrant Retina-Specific Differentiation Program and Cataract
    www.nature.com/scientificreports OPEN Absence of S100A4 in the mouse lens induces an aberrant retina‑specifc diferentiation program and cataract Rupalatha Maddala1*, Junyuan Gao2, Richard T. Mathias2, Tylor R. Lewis1, Vadim Y. Arshavsky1,3, Adriana Levine4, Jonathan M. Backer4,5, Anne R. Bresnick4 & Ponugoti V. Rao1,3* S100A4, a member of the S100 family of multifunctional calcium‑binding proteins, participates in several physiological and pathological processes. In this study, we demonstrate that S100A4 expression is robustly induced in diferentiating fber cells of the ocular lens and that S100A4 (−/−) knockout mice develop late‑onset cortical cataracts. Transcriptome profling of lenses from S100A4 (−/−) mice revealed a robust increase in the expression of multiple photoreceptor‑ and Müller glia‑specifc genes, as well as the olfactory sensory neuron‑specifc gene, S100A5. This aberrant transcriptional profle is characterized by corresponding increases in the levels of proteins encoded by the aberrantly upregulated genes. Ingenuity pathway network and curated pathway analyses of diferentially expressed genes in S100A4 (−/−) lenses identifed Crx and Nrl transcription factors as the most signifcant upstream regulators, and revealed that many of the upregulated genes possess promoters containing a high‑density of CpG islands bearing trimethylation marks at histone H3K27 and/or H3K4, respectively. In support of this fnding, we further documented that S100A4 (−/−) knockout lenses have altered levels of trimethylated H3K27 and H3K4. Taken together,
    [Show full text]
  • S100A4 Purified Maxpab Mouse Polyclonal Antibody (B03P)
    S100A4 purified MaxPab mouse polyclonal antibody (B03P) Catalog # : H00006275-B03P 規格 : [ 50 ug ] List All Specification Application Image Product Mouse polyclonal antibody raised against a full-length human S100A4 Western Blot (Transfected lysate) Description: protein. Immunogen: S100A4 (NP_002952.1, 1 a.a. ~ 101 a.a) full-length human protein. Sequence: MACPLEKALDVMVSTFHKYSGKEGDKFKLNKSELKELLTRELPSFLGKR TDEAAFQKLMSNLDSNRDNEVDFQEYCVFLSCIAMMCNEFFEGFPDKQ PRKK enlarge Host: Mouse Reactivity: Human Quality Control Antibody reactive against mammalian transfected lysate. Testing: Storage Buffer: In 1x PBS, pH 7.4 Storage Store at -20°C or lower. Aliquot to avoid repeated freezing and thawing. Instruction: MSDS: Download Datasheet: Download Applications Western Blot (Transfected lysate) Western Blot analysis of S100A4 expression in transfected 293T cell line (H00006275-T05) by S100A4 MaxPab polyclonal antibody. Lane 1: S100A4 transfected lysate(11.70 KDa). Lane 2: Non-transfected lysate. Protocol Download Gene Information Entrez GeneID: 6275 Page 1 of 2 2016/5/21 GeneBank NM_002961.2 Accession#: Protein NP_002952.1 Accession#: Gene Name: S100A4 Gene Alias: 18A2,42A,CAPL,FSP1,MTS1,P9KA,PEL98 Gene S100 calcium binding protein A4 Description: Omim ID: 114210 Gene Ontology: Hyperlink Gene Summary: The protein encoded by this gene is a member of the S100 family of proteins containing 2 EF-hand calcium-binding motifs. S100 proteins are localized in the cytoplasm and/or nucleus of a wide range of cells, and involved in the regulation of a number of cellular processes such as cell cycle progression and differentiation. S100 genes include at least 13 members which are located as a cluster on chromosome 1q21. This protein may function in motility, invasion, and tubulin polymerization.
    [Show full text]
  • Inhibits the Migration of Prostate Cancer Through Reducing S100A4, S100A2, and S100P Expression
    5429 Original Article Knockdown of ferritin heavy chain (FTH) inhibits the migration of prostate cancer through reducing S100A4, S100A2, and S100P expression Cuixiu Lu1, Huijun Zhao2, Chenshuo Luo3, Ting Lei4, Man Zhang5,6,7^ 1Clinical Laboratory Medicine, Peking University Ninth School of Clinical Medicine, Beijing, China; 2Clinical Laboratory Medicine, Capital Medical University, Beijing, China; 3Clinical Laboratory Medicine, Peking University Ninth School of Clinical Medicine, Beijing, China; 4Beijing Shijitan Hospital, Capital Medical University, Beijing, China; 5Clinical Laboratory Medicine, Peking University Ninth School of Clinical Medicine, Beijing, China; 6Beijing Shijitan Hospital, Capital Medical University, Beijing, China; 7Beijing Key Laboratory of Urinary Cellular Molecular Diagnostics, Beijing, China Contributions: (I) Conception and design: C Lu, C Luo; (II) Administrative support: M Zhang; (III) Provision of study materials or patients: C Lu, T Lei; (IV) Collection and assembly of data: C Lu, H Zhao; (V) Data analysis and interpretation: All authors; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors. Correspondence to: Man Zhang. Clinical Laboratory Medicine, Peking University Ninth School of Clinical Medicine, Beijing 100038, China. Email: [email protected]. Background: Ferritin plays a key role in the development of prostate cancer (PCa). Our earlier studies showed that the knockdown of ferritin heavy chain (FTH) suppressed the migration and invasion of the prostate cancer cell line (PC3). However, the mechanisms behind FTH in the cell migration regulation of PCa have not been thoroughly investigated. Methods: Isobaric tags for relative and absolute quantitation (iTRAQ) proteomics was used to analyze the protein expression in PC3 cells with FTH knockdown by small interfering RNAs and negative control cells.
    [Show full text]
  • Increased S100B Blood Levels in Unmedicated and Treated
    Molecular Psychiatry (2001) 6, 445–449 2001 Nature Publishing Group All rights reserved 1359-4184/01 $15.00 www.nature.com/mp ORIGINAL RESEARCH ARTICLE Increased S100B blood levels in unmedicated and treated schizophrenic patients are correlated with negative symptomatology M Rothermundt1, U Missler2, V Arolt1, M Peters1, J Leadbeater3, M Wiesmann2, S Rudolf4, KP Wandinger5 and H Kirchner4 1Department of Psychiatry, University of Muenster School of Medicine, Albert-Schweitzer-Str 11, D-48129 Muenster, Germany; 2Department of Neuroradiology, Medical University of Luebeck, Ratzeburger Allee 160, D-23538 Luebeck, Germany; 3Psychiatric Hospital, Friedrich-Ebert-Str, D-23774 Heiligenhafen, Germany; 4Institute of Immunology and Transfusion Medicine, Medical University of Luebeck, Ratzeburger Allee 160, D-23538 Luebeck, Germany; 5Department of Neurology, Charite Campus Mitte, NWFZ 2680, R 04 023, Schumannstr 20/21, D-10117 Berlin, Germany Keywords: nerve tissue protein S100; schizophrenia; anti- The term S100 comprises a heterogeneous family of psychotic agents; negative symptomatology; psychiatric acidic calcium-binding proteins of which the two pro- status teins S100A1 and S100B are considered to be the most S100B, a calcium-binding protein produced by astroglial relevant members regarding neurological disease.3 cells, is a marker of astroglial cellular integrity. It has S100B predominates in the brain. S100A1 and S100B been shown to be increased in acute brain damage and form dimeric proteins with a molecular weight of 21 neurodegeneration. A recent study showed increased kDA, which have previously been named S100a S100B levels in medicated acutely psychotic patients (S100A1–S100B), S100b (S100B–S100B), and S100a0 with schizophrenia. The study presented here included (S100A–S100A).4 S100B is synthesized mainly by 26 drug-free patients with acute schizophrenia and 26 astrocytes and evolves paracrine and autocrine effects matched healthy controls.
    [Show full text]
  • Preclinical Model Systems of Ryanodine Receptor 1-Related Myopathies and Malignant Hyperthermia
    Lawal et al. Orphanet Journal of Rare Diseases (2020) 15:113 https://doi.org/10.1186/s13023-020-01384-x REVIEW Open Access Preclinical model systems of ryanodine receptor 1-related myopathies and malignant hyperthermia: a comprehensive scoping review of works published 1990– 2019 Tokunbor A. Lawal1, Emily S. Wires2, Nancy L. Terry3, James J. Dowling4 and Joshua J. Todd1* Abstract Background: Pathogenic variations in the gene encoding the skeletal muscle ryanodine receptor (RyR1) are associated with malignant hyperthermia (MH) susceptibility, a life-threatening hypermetabolic condition and RYR1- related myopathies (RYR1-RM), a spectrum of rare neuromuscular disorders. In RYR1-RM, intracellular calcium dysregulation, post-translational modifications, and decreased protein expression lead to a heterogenous clinical presentation including proximal muscle weakness, contractures, scoliosis, respiratory insufficiency, and ophthalmoplegia. Preclinical model systems of RYR1-RM and MH have been developed to better understand underlying pathomechanisms and test potential therapeutics. Methods: We conducted a comprehensive scoping review of scientific literature pertaining to RYR1-RM and MH preclinical model systems in accordance with the PRISMA Scoping Reviews Checklist and the framework proposed by Arksey and O’Malley. Two major electronic databases (PubMed and EMBASE) were searched without language restriction for articles and abstracts published between January 1, 1990 and July 3, 2019. Results: Our search yielded 5049 publications from which 262 were included in this review. A majority of variants tested in RYR1 preclinical models were localized to established MH/central core disease (MH/CCD) hot spots. A total of 250 unique RYR1 variations were reported in human/rodent/porcine models with 95% being missense substitutions.
    [Show full text]
  • DIPPER, a Spatiotemporal Proteomics Atlas of Human Intervertebral Discs
    TOOLS AND RESOURCES DIPPER, a spatiotemporal proteomics atlas of human intervertebral discs for exploring ageing and degeneration dynamics Vivian Tam1,2†, Peikai Chen1†‡, Anita Yee1, Nestor Solis3, Theo Klein3§, Mateusz Kudelko1, Rakesh Sharma4, Wilson CW Chan1,2,5, Christopher M Overall3, Lisbet Haglund6, Pak C Sham7, Kathryn Song Eng Cheah1, Danny Chan1,2* 1School of Biomedical Sciences, , The University of Hong Kong, Hong Kong; 2The University of Hong Kong Shenzhen of Research Institute and Innovation (HKU-SIRI), Shenzhen, China; 3Centre for Blood Research, Faculty of Dentistry, University of British Columbia, Vancouver, Canada; 4Proteomics and Metabolomics Core Facility, The University of Hong Kong, Hong Kong; 5Department of Orthopaedics Surgery and Traumatology, HKU-Shenzhen Hospital, Shenzhen, China; 6Department of Surgery, McGill University, Montreal, Canada; 7Centre for PanorOmic Sciences (CPOS), The University of Hong Kong, Hong Kong Abstract The spatiotemporal proteome of the intervertebral disc (IVD) underpins its integrity *For correspondence: and function. We present DIPPER, a deep and comprehensive IVD proteomic resource comprising [email protected] 94 genome-wide profiles from 17 individuals. To begin with, protein modules defining key †These authors contributed directional trends spanning the lateral and anteroposterior axes were derived from high-resolution equally to this work spatial proteomes of intact young cadaveric lumbar IVDs. They revealed novel region-specific Present address: ‡Department profiles of regulatory activities
    [Show full text]
  • Human S100A4 Peptide (DAG-P1957) This Product Is for Research Use Only and Is Not Intended for Diagnostic Use
    Human S100A4 peptide (DAG-P1957) This product is for research use only and is not intended for diagnostic use. PRODUCT INFORMATION Antigen Description The protein encoded by this gene is a member of the S100 family of proteins containing 2 EF- hand calcium-binding motifs. S100 proteins are localized in the cytoplasm and/or nucleus of a wide range of cells, and involved in the regulation of a number of cellular processes such as cell cycle progression and differentiation. S100 genes include at least 13 members which are located as a cluster on chromosome 1q21. This protein may function in motility, invasion, and tubulin polymerization. Chromosomal rearrangements and altered expression of this gene have been implicated in tumor metastasis. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Jul 2008] Specificity Ubiquitously expressed. Nature Synthetic Expression System N/A Conjugate Unconjugated Sequence Similarities Belongs to the S-100 family.Contains 2 EF-hand domains. Procedure None Format Liquid Preservative None Storage Shipped at 4°C. Upon delivery aliquot and store at -20°C or -80°C. Avoid repeated freeze / thaw cycles. Information available upon request. ANTIGEN GENE INFORMATION Gene Name S100A4 S100 calcium binding protein A4 [ Homo sapiens (human) ] Official Symbol S100A4 Synonyms S100A4; S100 calcium binding protein A4; 42A; 18A2; CAPL; FSP1; MTS1; P9KA; PEL98; protein S100-A4; protein Mts1; fibroblast-specific protein-1; placental calcium-binding protein; malignant
    [Show full text]
  • CD29 Identifies IFN-Γ–Producing Human CD8+ T Cells with an Increased Cytotoxic Potential
    + CD29 identifies IFN-γ–producing human CD8 T cells with an increased cytotoxic potential Benoît P. Nicoleta,b, Aurélie Guislaina,b, Floris P. J. van Alphenc, Raquel Gomez-Eerlandd, Ton N. M. Schumacherd, Maartje van den Biggelaarc,e, and Monika C. Wolkersa,b,1 aDepartment of Hematopoiesis, Sanquin Research, 1066 CX Amsterdam, The Netherlands; bLandsteiner Laboratory, Oncode Institute, Amsterdam University Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands; cDepartment of Research Facilities, Sanquin Research, 1066 CX Amsterdam, The Netherlands; dDivision of Molecular Oncology and Immunology, Oncode Institute, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands; and eDepartment of Molecular and Cellular Haemostasis, Sanquin Research, 1066 CX Amsterdam, The Netherlands Edited by Anjana Rao, La Jolla Institute for Allergy and Immunology, La Jolla, CA, and approved February 12, 2020 (received for review August 12, 2019) Cytotoxic CD8+ T cells can effectively kill target cells by producing therefore developed a protocol that allowed for efficient iso- cytokines, chemokines, and granzymes. Expression of these effector lation of RNA and protein from fluorescence-activated cell molecules is however highly divergent, and tools that identify and sorting (FACS)-sorted fixed T cells after intracellular cytokine + preselect CD8 T cells with a cytotoxic expression profile are lacking. staining. With this top-down approach, we performed an un- + Human CD8 T cells can be divided into IFN-γ– and IL-2–producing biased RNA-sequencing (RNA-seq) and mass spectrometry cells. Unbiased transcriptomics and proteomics analysis on cytokine- γ– – + + (MS) analyses on IFN- and IL-2 producing primary human producing fixed CD8 T cells revealed that IL-2 cells produce helper + + + CD8 Tcells.
    [Show full text]