DOCSLIB.ORG

Urine RAS Components in Mice and People with Type 1 Diabetes and Chronic Kidney Disease

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Urine RAS Components in Mice and People with Type 1 Diabetes and Chronic Kidney Disease Articles in PresS. Am J Physiol Renal Physiol (May 3, 2017). doi:10.1152/ajprenal.00074.2017 Title: Urine RAS components in mice and people with type 1 diabetes and chronic kidney disease Running title: Urine RAS components in diabetic kidney disease Authors: Jan Wysocki, MD-PhD, Division of Nephrology and Hypertension, Department of Medicine, The Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA Anne Goodling, BA. Kidney Research Institute and Division of Nephrology, Department of Medicine, University of Washington, Seattle, WA Mar Burgaya, Division of Nephrology and Hypertension, Department of Medicine, The Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA Kathryn Whitlock, MS. Center for Child Health, Behavior and Development, Seattle Children's Research Institute, Seattle, WA John Ruzinski, BS. Kidney Research Institute and Division of Nephrology, Department of Medicine, University of Washington, Seattle, WA Daniel Batlle, MD, Division of Nephrology and Hypertension, Department of Medicine, The Feinberg School of Medicine, Northwestern University, Chicago, IL 60611 Maryam Afkarian, MD-PhD, Division of Nephrology, Department of Medicine, University of California, Davis, CA 95616 Corresponding author: Maryam Afkarian, MD-PhD, 4150 V Street, Suite 3500, Sacramento, CA 95817. Telephone: (916) 734-3774 Fax: (916) 734-7920. Email: [email protected]. Abstract word count: 250 Key words: diabetic kidney disease, renin angiotensin system, angiotensinogen, cathepsin D, angiotensin converting enzyme, angiotensin converting enzyme 2, aminopeptidase-A 1 Copyright © 2017 by the American Physiological Society. 1 ABSTRACT 2 The pathways implicated in diabetic kidney disease (DKD) are largely derived from animal models. To examine 3 if alterations in renin-angiotensin system (RAS) in humans are concordant with rodent models, we measured 4 concentration of angiotensinogen (AOG), cathepsin D (CTSD), angiotensin converting enzyme (ACE) and 5 ACE2 and enzymatic activities of ACE, ACE2 and aminopeptidase-A in FVB mice 13-20 weeks after treatment 6 with streptozotocin (n=9) or vehicle (n=15) and people with longstanding type 1 diabetes, with (n=37) or 7 without (n=81) DKD. In streptozotocin-treated mice, urine AOG and CTSD were 10.4- and 3.0-fold higher than 8 controls, respectively (p-values <0.001). Enzymatic activities of ACE, ACE2 and APA were 6.2-, 3.2- and 18.8- 9 fold higher, respectively, in diabetic animals (p-values <0.001). Angiotensin II was 2.4-fold higher in diabetic 10 animals (p-value 0.017). Compared to people without DKD, those with DKD had higher urine AOG (170 vs. 15 11 μg/g) and CTSD (147 vs. 31 μg/g). In people with DKD, urine ACE concentration was 1.8-fold higher (1.4 vs. 12 0.8 μg/g in those without DKD), while its enzymatic activity was 0.6-fold lower (1.0 vs. 1.6 x 109 RFU/g in those 13 without DKD). Lower ACE activity, but not ACE protein concentration, was associated with ACE inhibitor 14 (ACEI) treatment. After adjustment for clinical covariates, AOG, CTSD, ACE concentration and ACE activity 15 remained associated with DKD. In conclusion, in mice with streptozotocin-induced diabetes and humans with 16 DKD, urine concentrations and enzymatic activities of several RAS components are concordantly increased, 17 consistent with enhanced RAS activity and greater angiotensin II formation. ACEI use was associated with a 18 specific reduction in urine ACE activity, not ACE protein concentration, suggesting it may be a marker of 19 exposure to this widely-used therapy. 2 20 INTRODUCTION 21 Diabetic kidney disease is the leading cause of chronic and end-stage kidney disease in the United States and 22 worldwide.(2) Several biological pathways are implicated in the pathogenesis of diabetic kidney disease (DKD). 23 This information is largely obtained from animal models of DKD. However, animal models only partially 24 recapitulate the pathology and pathophysiology of human DKD.(5, 50) As such, the timing and extent of activity 25 of these pathways in the course of human DKD is not known. Given the dearth of research biopsies in human 26 DKD, information on pathway activity in human kidney biopsies obtained throughout the course of DKD is not 27 currently available. 28 Urine is a readily available, non-invasive bio-fluid, which is extensively used in clinical medicine and now 29 increasingly utilized for biomarker discovery.(16) Though formed initially as a filtrate of plasma, urine protein 30 composition is subsequently influenced by secretory and reabsorptive activities of the cells lining the length of 31 the nephron. Urine albumin and total urine protein quantity is a powerful clinical risk stratifier not only for 32 progression of kidney disease but also heart disease and mortality.(36) More recent evidence suggests that 33 urine protein composition may be able to inform on the underlying intrarenal pathogenic mechanisms.(13, 18, 34 21, 57, 59) This potential would open up new diagnostic avenues for the use of urine protein composition as a 35 personalized assay for tailoring treatment of kidney disease to the pathways active in each individual at a given 36 time. 37 We sought to comprehensively examine urine concentrations, and when possible enzymatic activities, of key 38 renin angiotensin system (RAS) components in an animal model of DKD, the FVB mice treated with 39 streptozotocin, as well as people with type 1 diabetes and DKD, compared to those with longstanding type 1 40 diabetes and no DKD. The examined RAS components included angiotensinogen, angiotensin converting 41 enzyme (ACE), ACE2, as well as cathepsin D (CTSD). The latter is a lysosomal protein capable of cleaving 42 angiotensinogen to angiotensin I, enabling ACE-independent angiotensin II generation.(24) In addition, we 43 examined enzymatic activity of aminopeptidase A (APA), which regulates angiotensin II concentration by 44 catalyzing its degradation to angiotensin III.(56) The RAS was selected as an exemplary pathway because it is 45 presumed to be overactive in DKD kidneys and its pharmacological suppression is part of current standards of 3 46 care. Our findings show concordance between the urine concentration and enzymatic activity of RAS pathway 47 proteins and the known intrarenal pathway activity and between rodent DKD models and human DKD. 48 Furthermore, in humans with DKD, urine ACE activity shows a negative correlation with use of ACE inhibitors 49 that may reflect suppression of ACE activity at the kidney level by these agents. 4 50 MATERIALS AND METHODS 51 Study cohort 52 People with type 1 diabetes, who were seen in the Diabetes Care Center (University of Washington) for 53 outpatient endocrinology care, were approached for participation in the Kidney Research Institute Diabetic 54 Kidney Disease Repository (University of Washington) and were enrolled into the repository after providing 55 informed consent. Demographic and clinical information was obtained from the electronic medical records and 56 a questionnaire filled by the participants. DKD was defined as either a urine ACR ≥300 mg/g or an eGFR <60 57 mL/min per 1.73 m2 and ACR ≥30 mg/g. People with longstanding diabetes but no evidence of overt DKD were 58 those with ≥30 years of type 1 diabetes, estimated GFR >90 mL/min per 1.73 m2, and ACR <300 mg/g. 59 Demographic and clinical data (age, race, sex, diabetes duration and RAS inhibitor use) were obtained from 60 the electronic medical records and confirmed by patient questionnaires (race, diabetes duration and RAS 61 inhibitor use). Diabetes type was extracted from the clinical notes, as ascertained by the endocrinologists 62 caring for the patients. Hemoglobin A1c and serum creatinine were obtained from the electronic medical 63 records at a time closest to the date of urine sample collection. Glomerular filtration rate was calculated from 64 the serum creatinine using CKD-EPI formula. (26) 65 A random clean-catch, mid-stream urine sample was collected and stored at 4oC after collection, until 66 processed. Urine samples were centrifuged at 4,700g for 15 minutes at 4oC and the supernatant collected, 67 aliquoted and stored at -80oC. The mean (standard deviation, SD) time from sample collection to storage at - 68 80oC was 5.7 (2.0) hours. The use of human samples and data were approved by the Institutional Review 69 Board of the University of Washington. 70 Experimental animals 71 Female FVB mice were acquired from Jackson Laboratories (Bar Harbor, ME). Animals were housed at the 72 Center for Comparative Medicine at Northwestern University Feinberg School of Medicine. Animal care and 73 procedures were approved by the Institutional Animal Care and Use Committee at Northwestern University and 74 in accordance with the NIH Guide for the Care and Use of Laboratory Animals and the institutional, state, and 75 federal guidelines. Streptozotocin (150 mg/kg, Sigma Chemical, St. Louis, MO) dissolved in sodium citrate 5 76 buffer pH 4.5 (streptozotocin-treated mice) or sodium citrate buffer pH 4.5 alone (non-diabetic vehicle controls) 77 was injected in two intraperitoneal injections to female FVB mice at 19 and 20 weeks of age. Spot urines were 78 collected 13 and 20 weeks after the last streptozotocin or vehicle injection (at 32 and 40 weeks of age, 79 respectively) and stored at -80oC. 80 Laboratory measurements in mouse urine samples 81 Albumin was measured by a quantitative solid-phase sandwich enzyme-Linked immunosorbent assay (ELISA) 82 (Albuwell M, Exocell, Philadelphia, PA). Creatinine was measured using the Jaffe method (Creatinine 83 Companion, Exocell, Philadelphia, PA). AOG was measured using a quantitative solid-phase sandwich ELISA 84 (IBL-America, Minneapolis, MN). CTSD was measured using a sandwich ELISA (OriGene Technologies, Inc, 85 Rockville, MD). ACE activity was measured in a high-throughput fluorimetric assay that uses the substrate 86 hippuryl-L-histidyl-L-leucine, as previously described.(48) The concentration of affinity purified recombinant 87 testis ACE showed direct linear relationship to the production of L-histidyl-L-leucine within the range of 0–4 10-4 88 nmol ACE.
Load more

Recommended publications
  • Human Cathepsin A/ Lysosomal Carboxypeptidase a Antibody
    Human Cathepsin A/ Lysosomal Carboxypeptidase A Antibody Monoclonal Mouse IgG2A Clone # 179803 Catalog Number: MAB1049 DESCRIPTION Species Reactivity Human Specificity Detects human Cathepsin A/Lysosomal Carboxypeptidase A in direct ELISAs and Western blots. In Western blots, detects the single chain (55 kDa) and heavy chain (32 kDa) forms of recombinant human (rh) Cathepsin A. In Western blots, less than 5% cross­reactivity with rhCathepsin B, C, D, E, L, O, S, X and Z is observed and no cross­reactivity with the light chain (20 kDa) of rhCathepsin A is observed. Source Monoclonal Mouse IgG2A Clone # 179803 Purification Protein A or G purified from hybridoma culture supernatant Immunogen Mouse myeloma cell line NS0­derived recombinant human Cathepsin A/Lysosomal Carboxypeptidase A Ala29­Tyr480 (predicted) Accession # P10619 Formulation Lyophilized from a 0.2 μm filtered solution in PBS with Trehalose. See Certificate of Analysis for details. *Small pack size (­SP) is supplied either lyophilized or as a 0.2 μm filtered solution in PBS. APPLICATIONS Please Note: Optimal dilutions should be determined by each laboratory for each application. General Protocols are available in the Technical Information section on our website. Recommended Sample Concentration Western Blot 1 µg/mL Recombinant Human Cathepsin A/Lysosomal Carboxypeptidase A (Catalog # 1049­SE) Immunoprecipitation 25 µg/mL Conditioned cell culture medium spiked with Recombinant Human Cathepsin A/Lysosomal Carboxypeptidase A (Catalog # 1049­SE), see our available Western blot detection antibodies PREPARATION AND STORAGE Reconstitution Reconstitute at 0.5 mg/mL in sterile PBS. Shipping The product is shipped at ambient temperature. Upon receipt, store it immediately at the temperature recommended below.
    [Show full text]
  • Supplementary Table S4. FGA Co-Expressed Gene List in LUAD
    Supplementary Table S4. FGA co-expressed gene list in LUAD tumors Symbol R Locus Description FGG 0.919 4q28 fibrinogen gamma chain FGL1 0.635 8p22 fibrinogen-like 1 SLC7A2 0.536 8p22 solute carrier family 7 (cationic amino acid transporter, y+ system), member 2 DUSP4 0.521 8p12-p11 dual specificity phosphatase 4 HAL 0.51 12q22-q24.1histidine ammonia-lyase PDE4D 0.499 5q12 phosphodiesterase 4D, cAMP-specific FURIN 0.497 15q26.1 furin (paired basic amino acid cleaving enzyme) CPS1 0.49 2q35 carbamoyl-phosphate synthase 1, mitochondrial TESC 0.478 12q24.22 tescalcin INHA 0.465 2q35 inhibin, alpha S100P 0.461 4p16 S100 calcium binding protein P VPS37A 0.447 8p22 vacuolar protein sorting 37 homolog A (S. cerevisiae) SLC16A14 0.447 2q36.3 solute carrier family 16, member 14 PPARGC1A 0.443 4p15.1 peroxisome proliferator-activated receptor gamma, coactivator 1 alpha SIK1 0.435 21q22.3 salt-inducible kinase 1 IRS2 0.434 13q34 insulin receptor substrate 2 RND1 0.433 12q12 Rho family GTPase 1 HGD 0.433 3q13.33 homogentisate 1,2-dioxygenase PTP4A1 0.432 6q12 protein tyrosine phosphatase type IVA, member 1 C8orf4 0.428 8p11.2 chromosome 8 open reading frame 4 DDC 0.427 7p12.2 dopa decarboxylase (aromatic L-amino acid decarboxylase) TACC2 0.427 10q26 transforming, acidic coiled-coil containing protein 2 MUC13 0.422 3q21.2 mucin 13, cell surface associated C5 0.412 9q33-q34 complement component 5 NR4A2 0.412 2q22-q23 nuclear receptor subfamily 4, group A, member 2 EYS 0.411 6q12 eyes shut homolog (Drosophila) GPX2 0.406 14q24.1 glutathione peroxidase
    [Show full text]
  • ©Ferrata Storti Foundation
    Original Articles T-cell/histiocyte-rich large B-cell lymphoma shows transcriptional features suggestive of a tolerogenic host immune response Peter Van Loo,1,2,3 Thomas Tousseyn,4 Vera Vanhentenrijk,4 Daan Dierickx,5 Agnieszka Malecka,6 Isabelle Vanden Bempt,4 Gregor Verhoef,5 Jan Delabie,6 Peter Marynen,1,2 Patrick Matthys,7 and Chris De Wolf-Peeters4 1Department of Molecular and Developmental Genetics, VIB, Leuven, Belgium; 2Department of Human Genetics, K.U.Leuven, Leuven, Belgium; 3Bioinformatics Group, Department of Electrical Engineering, K.U.Leuven, Leuven, Belgium; 4Department of Pathology, University Hospitals K.U.Leuven, Leuven, Belgium; 5Department of Hematology, University Hospitals K.U.Leuven, Leuven, Belgium; 6Department of Pathology, The Norwegian Radium Hospital, University of Oslo, Oslo, Norway, and 7Department of Microbiology and Immunology, Rega Institute for Medical Research, K.U.Leuven, Leuven, Belgium Citation: Van Loo P, Tousseyn T, Vanhentenrijk V, Dierickx D, Malecka A, Vanden Bempt I, Verhoef G, Delabie J, Marynen P, Matthys P, and De Wolf-Peeters C. T-cell/histiocyte-rich large B-cell lymphoma shows transcriptional features suggestive of a tolero- genic host immune response. Haematologica. 2010;95:440-448. doi:10.3324/haematol.2009.009647 The Online Supplementary Tables S1-5 are in separate PDF files Supplementary Design and Methods One microgram of total RNA was reverse transcribed using random primers and SuperScript II (Invitrogen, Merelbeke, Validation of microarray results by real-time quantitative Belgium), as recommended by the manufacturer. Relative reverse transcriptase polymerase chain reaction quantification was subsequently performed using the compar- Ten genes measured by microarray gene expression profil- ative CT method (see User Bulletin #2: Relative Quantitation ing were validated by real-time quantitative reverse transcrip- of Gene Expression, Applied Biosystems).
    [Show full text]
  • Proteolytic Cleavage—Mechanisms, Function
    Review Cite This: Chem. Rev. 2018, 118, 1137−1168 pubs.acs.org/CR Proteolytic CleavageMechanisms, Function, and “Omic” Approaches for a Near-Ubiquitous Posttranslational Modification Theo Klein,†,⊥ Ulrich Eckhard,†,§ Antoine Dufour,†,¶ Nestor Solis,† and Christopher M. Overall*,†,‡ † ‡ Life Sciences Institute, Department of Oral Biological and Medical Sciences, and Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, British Columbia V6T 1Z4, Canada ABSTRACT: Proteases enzymatically hydrolyze peptide bonds in substrate proteins, resulting in a widespread, irreversible posttranslational modification of the protein’s structure and biological function. Often regarded as a mere degradative mechanism in destruction of proteins or turnover in maintaining physiological homeostasis, recent research in the field of degradomics has led to the recognition of two main yet unexpected concepts. First, that targeted, limited proteolytic cleavage events by a wide repertoire of proteases are pivotal regulators of most, if not all, physiological and pathological processes. Second, an unexpected in vivo abundance of stable cleaved proteins revealed pervasive, functionally relevant protein processing in normal and diseased tissuefrom 40 to 70% of proteins also occur in vivo as distinct stable proteoforms with undocumented N- or C- termini, meaning these proteoforms are stable functional cleavage products, most with unknown functional implications. In this Review, we discuss the structural biology aspects and mechanisms
    [Show full text]
  • Post Mortem Proteolytic Degradation of Myosin Heavy Chain in Skeletal Muscle of Atlantic Cod
    Faculty of Biosciences, Fisheries and Economics Norwegian College of Fishery Science Post mortem proteolytic degradation of myosin heavy chain in skeletal muscle of Atlantic cod Pål Anders Wang A dissertation for the degree of Philosophiae Doctor Spring 2011 Post mortem proteolytic degradation of myosin heavy chain in skeletal muscle of Atlantic cod. Pål Anders Wang A dissertation for the degree of philosophiae doctor University of Tromsø Faculty of Biosciences, Fisheries and Economics Norwegian college of Fishery Science Spring 2011 Contents 1 Acknowledgements.......................................................................................................... II 2 List of publications........................................................................................................ III 3 Sammendrag...................................................................................................................IV 4 Abstract............................................................................................................................ V 5 Introduction ...................................................................................................................... 1 5.1 Fish muscle structure and composition.................................................................. 1 5.1.1 General structure and composition ................................................................ 1 5.1.2 Myosin ............................................................................................................... 3 5.2 Post
    [Show full text]
  • Fibroblasts from the Human Skin Dermo-Hypodermal Junction Are
    cells Article Fibroblasts from the Human Skin Dermo-Hypodermal Junction are Distinct from Dermal Papillary and Reticular Fibroblasts and from Mesenchymal Stem Cells and Exhibit a Specific Molecular Profile Related to Extracellular Matrix Organization and Modeling Valérie Haydont 1,*, Véronique Neiveyans 1, Philippe Perez 1, Élodie Busson 2, 2 1, 3,4,5,6, , Jean-Jacques Lataillade , Daniel Asselineau y and Nicolas O. Fortunel y * 1 Advanced Research, L’Oréal Research and Innovation, 93600 Aulnay-sous-Bois, France; [email protected] (V.N.); [email protected] (P.P.); [email protected] (D.A.) 2 Department of Medical and Surgical Assistance to the Armed Forces, French Forces Biomedical Research Institute (IRBA), 91223 CEDEX Brétigny sur Orge, France; [email protected] (É.B.); [email protected] (J.-J.L.) 3 Laboratoire de Génomique et Radiobiologie de la Kératinopoïèse, Institut de Biologie François Jacob, CEA/DRF/IRCM, 91000 Evry, France 4 INSERM U967, 92260 Fontenay-aux-Roses, France 5 Université Paris-Diderot, 75013 Paris 7, France 6 Université Paris-Saclay, 78140 Paris 11, France * Correspondence: [email protected] (V.H.); [email protected] (N.O.F.); Tel.: +33-1-48-68-96-00 (V.H.); +33-1-60-87-34-92 or +33-1-60-87-34-98 (N.O.F.) These authors contributed equally to the work. y Received: 15 December 2019; Accepted: 24 January 2020; Published: 5 February 2020 Abstract: Human skin dermis contains fibroblast subpopulations in which characterization is crucial due to their roles in extracellular matrix (ECM) biology.
    [Show full text]
  • Was the Serine Protease Cathepsin G Discovered by S. G. Hedin in 1903
    Vol. 58, No 1/2011 39–44 on-line at: www.actabp.pl Regular paper Was the serine protease cathepsin G discovered by S. G. Hedin in 1903 in bovine spleen? David Palesch1, Marcin Sieńczyk2, Jozef Oleksyszyn2, Michael Reich1, Ewa Wieczerzak3, Bernhard O. Boehm1 and Timo Burster1* 1Division of Endocrinology and Diabetes, Department of Internal Medicine I, University Medical Center Ulm, Ulm, Germany; 2Wrocław University of Technology, Wrocław, Poland; 3Faculty of Chemistry, University of Gdansk, Gdańsk, Poland In the beginning of the 20th century, enzymes with pro- tive under acidic conditions, which he named b-protease teolytic activity were classified as peptidases, Erepsin, (Hedin, 1903a). and proteases. Among these, pepsin, trypsin, and auto- lytic enzymes were of the protease class. Spleen-derived After discovering these two proteases in bovine proteases were poorly characterized until Sven Gustaf spleen, Hedin performed further experiments with bo- Hedin performed several digestion experiments with vine serum and concluded that it contained a weak pro- bovine spleen. He incubated minced bovine spleen un- teolytic enzyme active in neutral medium, the activity of der acidic or neutral conditions and characterized two which could be blocked by heating at 55 °C or neutral- active proteases; the results were published in 1903. ized by antibodies (also named anti-enzymes at the time) The first protease was named α-protease and was ac- present in the serum. Hedin assumed that the α-protease tive under neutral conditions. The second was named in bovine spleen-derived leukocytes was similar to the β-protease and was active under acidic conditions. We protease found in serum.
    [Show full text]
  • Proteomics of the Lysosome
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector Biochimica et Biophysica Acta 1793 (2009) 625–635 Contents lists available at ScienceDirect Biochimica et Biophysica Acta journal homepage: www.elsevier.com/locate/bbamcr Review Proteomics of the lysosome Torben Lübke a, Peter Lobel b,c, David E. Sleat b,c,⁎ a Zentrum Biochemie und Molekulare Zellbiologie, Abteilung Biochemie II, Georg-August Universität Göttingen, 37073 Göttingen, Germany b Center for Advanced Biotechnology and Medicine, Piscataway, NJ 08854, USA c Department of Pharmacology, University of Medicine and Dentistry of New Jersey - Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA article info abstract Article history: Defects in lysosomal function have been associated with numerous monogenic human diseases typically Received 16 May 2008 classified as lysosomal storage diseases. However, there is increasing evidence that lysosomal proteins are Received in revised form 24 September 2008 also involved in more widespread human diseases including cancer and Alzheimer disease. Thus, there is a Accepted 30 September 2008 continuing interest in understanding the cellular functions of the lysosome and an emerging approach to this Available online 15 October 2008 is the identification of its constituent proteins by proteomic analyses. To date, the mammalian lysosome has been shown to contain ∼60 soluble luminal proteins and ∼25 transmembrane proteins. However, recent Keywords: fi fi Lysosomal protein proteomic studies based upon af nity puri cation of soluble components or subcellular fractionation to Proteomic obtain both soluble and membrane components suggest that there may be many more of both classes of Mass spectrometry protein resident within this organelle than previously appreciated.
    [Show full text]
  • Fish and Shellfish Immunology 92 (2019) 405–420
    Fish and Shellfish Immunology 92 (2019) 405–420 Contents lists available at ScienceDirect Fish and Shellfish Immunology journal homepage: www.elsevier.com/locate/fsi Full length article Differential proteomic profiles and characterizations between hyalinocytes and granulocytes in ivory shell Babylonia areolata T Guilan Dia, Yanfei Lia, Xianliang Zhaoa, Ning Wanga, Jingqiang Fub, Min Lib, Miaoqin Huangb, ∗ ∗∗ Weiwei Youb, Xianghui Konga, , Caihuan Keb, a College of Fisheries, Henan Normal University, Xinxiang, 453007, China b State Key Laboratory of Marine Environmental Science, College of Ocean and Earth Sciences, Xiamen University, Xiamen, China ARTICLE INFO ABSTRACT Keywords: The haemocytes of the ivory shell, Babylonia areolata are classified by morphologic observation into the fol- Babylonia areolata lowing types: hyalinocytes (H) and granulocytes (G). Haemocytes comprise diverse cell types with morpholo- Haemocytes gical and functional heterogene and play indispensable roles in immunological homeostasis of invertebrates. In Percoll density gradient centrifugation the present study, two types of haemocytes were morphologically identified and separated as H and G by Percoll Granulocytes density gradient centrifugation. The differentially expressed proteins were investigated between H and G using Hyalinocytes mass spectrometry. The results showed that total quantitative proteins between H and G samples were 1644, the Label-free quantification proteomics number of up-regulated proteins in G was 215, and the number of down-regulated proteins in G was 378. Among them, cathepsin, p38 MAPK, toll-interacting protein-like and beta-adrenergic receptor kinase 2-like were up- regulated in G; alpha-2-macroglobulin-like protein, C-type lectin, galectin-2-1, galectin-3, β-1,3-glucan-binding protein, ferritin, mega-hemocyanin, mucin-17-like, mucin-5AC-like and catalytic subunit of protein kinase A were down-regulated in G.
    [Show full text]
  • Protein-Reactive Natural Products Carmen Drahl, Benjamin F
    Reviews B. F. Cravatt, E. J. Sorensen, and C. Drahl DOI: 10.1002/anie.200500900 Natural Products Chemistry Protein-Reactive Natural Products Carmen Drahl, Benjamin F. Cravatt,* and Erik J. Sorensen* Keywords: enzymes · inhibitors · molecular probes · natural products · structure– activity relationships Angewandte Chemie 5788 www.angewandte.org 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim Angew. Chem. Int. Ed. 2005, 44, 5788 – 5809 Angewandte Enzyme Inhibitors Chemie Researchers in the post-genome era are confronted with the daunting From the Contents task of assigning structure and function to tens of thousands of encoded proteins. To realize this goal, new technologies are emerging 1. Introduction 5789 for the analysis of protein function on a global scale, such as activity- 2. Natural Products that Target based protein profiling (ABPP), which aims to develop active site- Catalytic Nucleophiles in directed chemical probes for enzyme analysis in whole proteomes. For Enzyme Active Sites 5790 the pursuit of such chemical proteomic technologies, it is helpful to derive inspiration from protein-reactive natural products. Natural 3. Natural Products that Target Non-Nucleophilic Residues in products use a remarkably diverse set of mechanisms to covalently Enzyme Active Sites 5794 modify enzymes from distinct mechanistic classes, thus providing a wellspring of chemical concepts that can be exploited for the design of 4. Targeting Nonenzymatic active-site-directed proteomic probes. Herein, we highlight several Proteins 5802 examples of protein-reactive natural products and illustrate how their 5. Summary and Outlook 5803 mechanisms of action have influenced and continue to shape the progression of chemical proteomic technologies like ABPP. 1.
    [Show full text]
  • Sialidases in Vertebrates: a Family of Enzymes Tailored for Several Cell Functions*
    Provided for non-commercial research and educational use only. Not for reproduction, distribution or commercial use. This chapter was originally published in the book Advances in Carbohydrate Chemistry and Biochemistry (Volume 64). The copy attached is provided by Elsevier for the author’s benefit and for the benefit of the author’s institution, for non-commercial research, and educational use. This includes without limitation use in instruction at your institution, distribution to specific colleagues, and providing a copy to your institution’s administrator. All other uses, reproduction and distribution, including without limitation commercial reprints, selling or licensing copies or access, or posting on open internet sites, your personal or institution’s website or repository, are prohibited. For exceptions, permission may be sought for such use through Elsevier's permissions site at: http://www.elsevier.com/locate/permissionusematerial From Eugenio Monti, Erik Bonten, Alessandra D’Azzo, Roberto Bresciani, Bruno Venerando, Giuseppe Borsani, Roland Schauer and Guido Tettamanti for Several Cell Functions. In: Derek Horton, editor, Advances in Carbohydrate Chemistry and Biochemistry (Volume 64). Academic Press, 2010, p. 402. ISBN: 978-0-12-380854-7 © Copyright 2010, Elsevier Inc. Academic Press. Author's personal copy ADVANCES IN CARBOHYDRATE CHEMISTRY AND BIOCHEMISTRY, VOL. 64 SIALIDASES IN VERTEBRATES: A FAMILY OF ENZYMES TAILORED * FOR SEVERAL CELL FUNCTIONS a b b a BY EUGENIO MONTI ,ERIK BONTEN ,ALESSANDRA D’AZZO ,ROBERTO BRESCIANI
    [Show full text]
  • Supplementary File 1 (PDF, 225 Kib)
    ("autophagy"[MeSH Terms] OR "autophagy"[All Fields] OR "lysosomes"[MeSH Terms] OR "lysosomes"[All Fields] OR (lysosomal[All Fields] AND ("enzymes"[MeSH Terms] OR "enzymes"[All Fields] OR "enzyme"[All Fields])) OR "mitochondrial degradation"[MeSH Terms] OR ("mitochondrial"[All Fields] AND "degradation"[All Fields]) OR "mitochondrial degradation"[All Fields] OR "mitophagy"[All Fields] OR (AGA[All Fields] OR ("aspartylglucosylaminase"[MeSH Terms] OR "aspartylglucosylaminase"[All Fields] OR "aspartylglucosaminidase"[All Fields])) OR (ARSA[All Fields] OR ("arylsulphatase a"[All Fields] OR "cerebroside-sulfatase"[MeSH Terms] OR "cerebroside-sulfatase"[All Fields] OR "arylsulfatase a"[All Fields])) OR (ARSB[All Fields] OR ("arylsulphatase b"[All Fields] OR "n- acetylgalactosamine-4-sulfatase"[MeSH Terms] OR "n-acetylgalactosamine-4-sulfatase"[All Fields] OR "arylsulfatase b"[All Fields])) OR (ASAH1[All Fields] OR ("ceramidases"[MeSH Terms] OR "ceramidases"[All Fields] OR "n acylsphingosine amidohydrolase"[All Fields])) OR ATP13A2[All Fields] OR CLN3[All Fields] OR CLN5[All Fields] OR CLN6[All Fields] OR CLN8[All Fields] OR (CTNS[All Fields] OR cystinosin[All Fields]) OR (CTSA[All Fields] OR "cathepsin a"[MeSH Terms] OR "cathepsin a"[All Fields]) OR (CTSD[All Fields] OR "cathepsin d"[MeSH Terms] OR "cathepsin d"[All Fields]) OR (CTSF[All Fields] OR "cathepsin f"[MeSH Terms] OR "cathepsin f"[All Fields]) OR (CTSF[All Fields] OR "cathepsin f"[MeSH Terms] OR "cathepsin f"[All Fields]) OR DNAJC5[All Fields] OR (FUCA1[All Fields] OR (("alpha-l-fucosidase"[MeSH
    [Show full text]