Genetic Control of Apigenin Di-C-Glycoside Biosynthesis in Bread Wheat Grain and Their Role

Total Page:16

File Type:pdf, Size:1020Kb

Genetic Control of Apigenin Di-C-Glycoside Biosynthesis in Bread Wheat Grain and Their Role Genetic control of Apigenin di-C-glycoside biosynthesis in bread wheat grain and their role as yellow pigments of Asian alkaline noodles Submitted by Grace Yasmein Wijaya This thesis is submitted to Faculty of Sciences in fulfilment of the requirements for the degree Doctor of Philosophy Faculty of Science The University of Adelaide November 2012 This book is An Answer to Prayers of a Long list of Believers I have been very blessed and loved with all of your spiritual supports, for His guidance and protections, and sincerely will not have enough to thank you all..... May you all be blessed and loved, too As I have been always, yasmein Table of Content Table of Content i List of Tables x List of Figures xiii List of Supplemental Materials xxv Summary xxx Statement of Authorship xxxiv List of Publications xxxv Acknowledgement xxxvi List of Abbreviations xxxix Chapter I: General Introduction 1 1.1 Background 1 1.2 Knowledge Gap 2 1.3 Structure of thesis 2 Chapter II: Literature review 4 2.1 Asian noodles as one of the major end-products of Australian bread wheat 4 2.2 Yellow colour of YAN 5 2.2.1 Natural Compounds that contribute to the yellow colour of YAN 5 2.2.1.1 Types of natural compounds that contributes to the yellow colour of YAN and their roles in plants and human health 5 2.2.1.2 Contribution of xanthophylls and ACGs to the yellow colour of alkaline noodles 8 2.2.2 Factors influencing the measurement of the yellowness of noodles and the content of xanthophyll and ACG in wheat grain 10 i 2.2.3 The amount, tissue location and composition of xanthophylls and apigenin di-C- glycosides in wheat grain and recovery in flour following milling 11 2.3 Apigenin di-C-glycoside biosynthesis in plants 12 2.3.1 Flavonoid biosynthetic pathway 12 2.3.2 Pathway leading to apigenin di-C-glycoside biosynthesis in wheat grain 15 2.3.3 UDP-sugar recognition by the glycosyltransferases 20 2.4 Genetic regulation of flavone biosynthesis in cereal grain 21 2.4.1 Genetic loci involved in the control of compounds related to the yellow colour of alkaline noodles 21 2.4.2 Transcriptional regulation of flavonoid biosynthesis 23 2.4.3 Transcription factors controlling flavonoid biosynthesis in cereal grain 24 2.5 Wheat genomics for studying genetic regulation of flavone-di-C-glycoside biosynthesis 27 2.5.1 Organization of the wheat genome and wheat genomic information 27 2.5.2 Methods for studying regulation of gene expression in wheat 30 2.5.2.1 Reverse and forward genetic approaches for studying regulation of gene expression in wheat 30 2.5.2.2 Identification of transcription factor genes through genetic mapping and positional cloning 31 2.5.2.3 Availability of resources for synteny analysis to determine transcription factor gene sequences 33 2.5.2.4 Transcript analysis of wheat genes 36 2.6 Conclusion 37 2.7 Research questions 38 2.8 Research aims 38 ii 2.9 Significance/contribution to the discipline 39 Chapter III: General Materials and Methods 40 3.1 Introduction 40 3.2 Plant Materials 40 3.2.1 Genetic resources for experiment 1 (Chapter IV): Survey of genetic variation in ACG content and composition 40 3.2.2 Genetic resources for experiment 2 (Chapter V): Quantitative assessment of content and composition of the ACGs and their contribution to YAN colour in comparison to that of lutein 41 3.2.3 Population for experiment 3 (Chapter VI): Genetic control of the ACG content and composition in bread wheat grain 42 3.2.3.1 Parents of Australian doubled haploid populations 42 3.2.3.2 Sunco/Tasman doubled haploid population used in the QTL mapping 42 3.2.3.3 Other genetic stocks used in marker analysis 44 3.3 Location, time, and condition of planting of the genetic resources 45 3.4 Phenotyping 46 3.4.1 Data collection 46 3.4.1.1 ACG analysis 46 3.4.1.2 The Use of Internal and external standard solutions in ACG Analyses 47 3.4.1.2.1 The use of vanillin internal standard in ACG analyses 47 3.4.1.2.2 The used of rutin internal standard 48 3.4.1.2.3 The use of rutin external standard 48 3.4.1.3 Hundred grain weight 48 3.4.2 Data Analysis 49 3.4.2.1 Calculations of ACG traits 49 iii 3.4.2.2 Statistical Analysis 50 Chapter IV: Apigenin di-C-glycosides (ACG) content and composition in grains of bread wheat (Triticum aestivum L.) and related species 53 4.1 Introduction 53 4.2 Material and Methods 54 4.2.1 Plant materials 54 4.2.2 Apigenin di-C-glycoside analysis 56 4.2.3 Experimental design and data analysis 56 4.3 Results and discussion 57 4.3.1 Apigenin di-C-diglycoside analysis 57 4.3.2 Apigenin di-C-glycoside concentration and content per grain 58 4.3.2.1 ACG concentration 58 4.3.2.2 ACG content per grain 60 4.3.2.3 ACG content of reciprocal F1 and parental grain 64 4.3.2.4 ACG content of nullisomic-tetrasomic lines of Chinese Spring and Chinese Spring/Triticum spelta chromosome substitution lines 66 4.3.2.5 Relative effects of genotype and environment on ACG content 66 4.3.3 Apigenin di-C-glycoside composition, ACG1/ACG2 67 4.3.3.1 ACG composition and pedigree of Triticum aestivum L. cultivars 68 4.3.3.2 ACG1/ACG2 ratio in reciprocal F1 grains and their parents 69 4.3.3.3 ACG composition of nullisomic-tetrasomic lines of Chinese Spring 69 4.3.3.4 Correlation among ACG components 71 4.4 Conclusions 72 Chapter V: Contribution of Apigenin di-C-glycoside (ACG) to the colour of yellow alkaline noodles (YAN) in comparison to that of Lutein 77 iv 5.1 Introduction 77 5.2 Materials and Methods 79 5.2.1 Plant materials 79 5.2.2 Preparation of flour and noodles 80 5.2.2.1 Grain milling 80 5.2.2.2 Preparation of noodle sheets 81 5.2.3 Measurement of colour of YAN and WSN 82 5.2.4 Analyses of yellow pigment content in grain and flour 83 5.2.4.1 ACG analysis of grain and flour 83 5.2.4.2 Lutein analysis of grain and flour 84 5.2.4.2.1 Lutein extraction and analyses 84 5.2.4.2.2 The use of internal and external standard solutions in lutein analyses 85 The use of -apo-8’-carotenal as internal standard 85 The use of xanthophylls to construct the standard curves 86 5.2.5 Estimation of ACG contribution to yellowness of YAN 86 5.2.6 Data analysis 87 5.3 Results and Discussion 88 5.3.1 ACG and lutein content in wheat grain and flour 88 5.3.1.1 The effect of milling on the proportion of ACG and lutein in relation to their tissue location in the grains 87 5.3.1.2 Comparison of Bühler and Quadrumat Junior Mills 92 5.3.1.3 The influence of grain physical properties on milling 93 5.3.2 Yellowness of YAN and its correlation with lutein and ACG concentration 97 5.3.3 Yellow colour developed in the presence of alkaline salts 98 5.3.4 Prediction of the contribution of ACG to b* (YAN-WSN) 102 v 5.3.5 Contribution of ACG to b*(YAN –WSN) 103 5.4 Conclusions 105 Chapter VI: QTL associated with Apigenin di-C-glycoside (ACG) concentration and composition in bread wheat (Triticum aestivum L.) grain and identification of candidate genes 111 6.1 Introduction 111 6.2 Material and methods 113 6.2.1 Plant material 113 6.2.2 Validation of the QTL associated with variation in ACG composition, ACG concentration, and 100 grain weight in the Sunco/Tasman 114 6.2.2.1 Construction of new genetic maps for Sunco/Tasman incorporating additional markers 114 6.2.2.2 QTL analyses of ACG concentration, ACG composition and 100 grain weight. 115 6.2.3 Addition of markers to the major QTL for ACG concentration and composition located on 7BS 116 6.2.3.1 DNA Isolation 116 6.2.3.2 SSR marker analysis 117 Polymorphism test 117 Mapping polymorphic markers in the Sunco/Tasman doubled haploid population 118 6.2.3.3 Single nucleotide polymorphism (SNP) marker analysis 119 Source of SNPs 119 SNP marker analysis 119 6.2.3.4 Apigenin-C-diglycoside analysis 122 6.2.3.5 Linkage mapping and QTL analysis 122 vi Comparison of 7BS of Sunco/Tasman with other wheat maps 123 6.2.4 Synteny between wheat, rice and Brachypodium distachyon 123 6.2.4.1 Wheat 7BS and rice chromosomes 6 and 8 123 6.2.4.2 Wheat and Brachypodium distachyon 124 6.2.5 Multiple alignment and structural analysis of candidate sequences 124 6.3 Results and discussion 125 6.3.1 ACG content and composition of Sunco/Tasman parents and doubled haploid population 125 6.3.2 QTL for ACG content and composition in Sunco/Tasman 128 6.3.3 Fine mapping of ACG QTL on 7BS of Sunco/Tasman 132 6.3.3.1 Additional markers 132 6.3.3.2 The order of SSR markers within the QTL on 7BS of Sunco/Tasman compared with other populations and a consensus map 135 6.3.3.3 QTL for the ACG traits 135 6.3.4 Synteny between the wheat 7BS chromosome region harbouring the QTL associated with variation in ACG traits with the physical maps of rice and Brachypodium distachyon 141 6.3.4.1 Synteny with rice chromosomes 6 and 8 141 6.3.4.2 Synteny with Brachypodium distachyon chromosomes 1 and 3 147 6.3.5 Candidate genes related to variation in ACG biosynthesis in wheat 151 6.3.5.1 The glycosyltransferases 151 6.3.5.2 Other candidate genes for the major and minor QTL associated with ACG content and composition.
Recommended publications
  • Inositol Safety: Clinical Evidences
    European Review for Medical and Pharmacological Sciences 2011; 15: 931-936 Inositol safety: clinical evidences G. CARLOMAGNO, V. UNFER AGUNCO Obstetrics & Gynecology Center, Rome (Italy) Abstract. – Myo-inositol is a six carbon ent required by the human cells for the growth cyclitol that contains five equatorial and one axi- and survival in the culture. In humans and other al hydroxyl groups. Myo-inositol has been classi- species, Myo-inositol can be converted to either fied as an insulin sensitizing agent and it is L- or D-chiro-inositol by epimerases. Early stud- commonly used in the treatment of the Polycys- tic Ovary Syndrome (PCOS). However, despite ies showed that inositol urinary clearance was al- its wide clinical use, there is still scarce informa- tered in type 2 diabetes patients, the next step tion on the myo-inositol safety and/or side ef- was to link impaired inositol clearance with in- fects. The aim of the present review was to sum- sulin resistance (for a review see1). Because of marize and discuss available data on the myo-in- these properties, inositol have been classified as ositol safety both in non-clinical and clinical set- “insulin sensitizing agent”2. tings. The main outcome was that only the highest In the recent years, inositol has found more dose of myo-inositol (12 g/day) induced mild and more space in the reproductive clinical prac- gastrointestinal side effects such as nausea, fla- tice3-6. Indeed, since the main therapy for Poly- tus and diarrhea. The severity of side effects did cystic Ovary Syndrome (PCOS) is the use of in- not increase with the dosage.
    [Show full text]
  • Revisions to USP 31–NF 26, Second Supplement
    Revisions to USP 31–NF 26, Second Supplement (published May 2008) Published April 2008 General Chapters Monographs:A–C D–N O–S T–Z Monograph Title Section Head Scientific Liaison DANTROLENE SODIUM Dissolution <711> CAPSULES PF 33(4) Pg. 645 DEHYDROACETIC ACID PF 33(4) Title Pg. 703 DEHYDROACETIC ACID PF 33(4) Chemical Info Pg. 703 DEHYDROACETIC ACID PF 33(4) Definition Pg. 703 DEHYDROACETIC ACID PF 33(4) Packaging and storage Pg. 703 DEHYDROACETIC ACID PF 33(4) USP Reference standards <11> Pg. 703 DEHYDROACETIC ACID PF 33(4) Identification Pg. 703 DEHYDROACETIC ACID PF 33(4) Heavy Metals, Method II <231> Pg. 703 DEHYDROACETIC ACID PF 33(4) Loss on drying <731> Pg. 703 DEHYDROACETIC ACID PF 33(4) Melting range, Class I <741> Pg. 703 DEHYDROACETIC ACID PF 33(4) Residue on ignition <281> Pg. 703 DEHYDROACETIC ACID PF 33(4) Assay Pg. 703 DIDANOSINE TABLETS FOR ORAL SUSPENSION PF 32(3) Pg. Title 784 DIDANOSINE TABLETS FOR ORAL SUSPENSION PF 32(3) Pg. Definition 784 file:///C|/Documents%20and%20Settings/rwt/Desktop/revisions/usp31nf26secondSupplement03.html[4/26/2011 1:18:07 PM] DIDANOSINE TABLETS FOR ORAL SUSPENSION PF 32(3) Pg. Packaging and storage 784 DIDANOSINE TABLETS FOR ORAL SUSPENSION PF 32(3) Pg. Labeling 784 DIDANOSINE TABLETS FOR ORAL SUSPENSION PF 32(3) Pg. USP Reference stadards 784 DIDANOSINE TABLETS FOR ORAL SUSPENSION PF 32(3) Pg. Identification 784 DIDANOSINE TABLETS FOR ORAL SUSPENSION PF 32(3) Pg. Uniformity of dosage units 784 DIDANOSINE TABLETS FOR ORAL SUSPENSION PF 32(3) Pg. Loss on drying 784 DIDANOSINE TABLETS FOR ORAL SUSPENSION PF 32(3) Pg.
    [Show full text]
  • Maize (Zea Mays L.) Nucleoskeletal Proteins Regulate Nuclear Envelope 2 Remodeling and Function in Stomatal Complex Development and Pollen Viability
    bioRxiv preprint doi: https://doi.org/10.1101/2020.12.23.424208; this version posted December 24, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. 1 Maize (Zea mays L.) nucleoskeletal proteins regulate nuclear envelope 2 remodeling and function in stomatal complex development and pollen viability. 3 McKenna JF*✝, Gumber HK*, Turpin ZM, Jalovec AM, Kartick AC, Graumann K#, and 4 Bass HW# 5 *co-first authors, equal contributions 6 # co-corresponding authors 7 8 email addresses: 9 10 Joseph F. McKenna, [email protected], Department of Biological and 11 Medical Sciences, Oxford Brookes University, Oxford, UK 12 ✝ Current address: [email protected], School of Life Sciences, University 13 of Warwick, Coventry, CV4 7AL, UK, ORCID 0000-0003-4838-6048 14 15 Hardeep K. Gumber, [email protected], Department of Biological Science, Florida 16 State University, Tallahassee, FL, USA, ORCID 0000-0001-5250-7207 17 18 Zachary M. Turpin, [email protected], Department of Biological Science, Florida State 19 University, Tallahassee, FL, USA 20 21 Alexis M. Jalovec, [email protected], Department of Biological Science, Florida State 22 University, Tallahassee, FL, USA 23 24 Andre C. Kartick, [email protected], Department of Biological Science, Florida State 25 University, Tallahassee, FL, USA 26 Katja Graumann, [email protected], Department of Biological and Medical 27 Sciences, Oxford Brookes University, Oxford, UK 28 Hank W.
    [Show full text]
  • Evolutionary Genomics of a Plastic Life History Trait: Galaxias Maculatus Amphidromous and Resident Populations
    EVOLUTIONARY GENOMICS OF A PLASTIC LIFE HISTORY TRAIT: GALAXIAS MACULATUS AMPHIDROMOUS AND RESIDENT POPULATIONS by María Lisette Delgado Aquije Submitted in partial fulfilment of the requirements for the degree of Doctor of Philosophy at Dalhousie University Halifax, Nova Scotia August 2021 Dalhousie University is located in Mi'kma'ki, the ancestral and unceded territory of the Mi'kmaq. We are all Treaty people. © Copyright by María Lisette Delgado Aquije, 2021 I dedicate this work to my parents, María and José, my brothers JR and Eduardo for their unconditional love and support and for always encouraging me to pursue my dreams, and to my grandparents Victoria, Estela, Jesús, and Pepe whose example of perseverance and hard work allowed me to reach this point. ii TABLE OF CONTENTS LIST OF TABLES ............................................................................................................ vii LIST OF FIGURES ........................................................................................................... ix ABSTRACT ...................................................................................................................... xii LIST OF ABBREVIATION USED ................................................................................ xiii ACKNOWLEDGMENTS ................................................................................................ xv CHAPTER 1. INTRODUCTION ....................................................................................... 1 1.1 Galaxias maculatus ..................................................................................................
    [Show full text]
  • )&F1y3x PHARMACEUTICAL APPENDIX to THE
    )&f1y3X PHARMACEUTICAL APPENDIX TO THE HARMONIZED TARIFF SCHEDULE )&f1y3X PHARMACEUTICAL APPENDIX TO THE TARIFF SCHEDULE 3 Table 1. This table enumerates products described by International Non-proprietary Names (INN) which shall be entered free of duty under general note 13 to the tariff schedule. The Chemical Abstracts Service (CAS) registry numbers also set forth in this table are included to assist in the identification of the products concerned. For purposes of the tariff schedule, any references to a product enumerated in this table includes such product by whatever name known. Product CAS No. Product CAS No. ABAMECTIN 65195-55-3 ACTODIGIN 36983-69-4 ABANOQUIL 90402-40-7 ADAFENOXATE 82168-26-1 ABCIXIMAB 143653-53-6 ADAMEXINE 54785-02-3 ABECARNIL 111841-85-1 ADAPALENE 106685-40-9 ABITESARTAN 137882-98-5 ADAPROLOL 101479-70-3 ABLUKAST 96566-25-5 ADATANSERIN 127266-56-2 ABUNIDAZOLE 91017-58-2 ADEFOVIR 106941-25-7 ACADESINE 2627-69-2 ADELMIDROL 1675-66-7 ACAMPROSATE 77337-76-9 ADEMETIONINE 17176-17-9 ACAPRAZINE 55485-20-6 ADENOSINE PHOSPHATE 61-19-8 ACARBOSE 56180-94-0 ADIBENDAN 100510-33-6 ACEBROCHOL 514-50-1 ADICILLIN 525-94-0 ACEBURIC ACID 26976-72-7 ADIMOLOL 78459-19-5 ACEBUTOLOL 37517-30-9 ADINAZOLAM 37115-32-5 ACECAINIDE 32795-44-1 ADIPHENINE 64-95-9 ACECARBROMAL 77-66-7 ADIPIODONE 606-17-7 ACECLIDINE 827-61-2 ADITEREN 56066-19-4 ACECLOFENAC 89796-99-6 ADITOPRIM 56066-63-8 ACEDAPSONE 77-46-3 ADOSOPINE 88124-26-9 ACEDIASULFONE SODIUM 127-60-6 ADOZELESIN 110314-48-2 ACEDOBEN 556-08-1 ADRAFINIL 63547-13-7 ACEFLURANOL 80595-73-9 ADRENALONE
    [Show full text]
  • Thesis Was Carried out at the Centre for Geobiology and Department of Biology at the University of Bergen
    The Arctic Mid-Ocean Ridge Vent Fields – A valuable Resource for Marine Bioprospecting? Juliane Wissuwa Dissertation for the degree of philosophiae doctor (PhD) at the University of Bergen 2016 Dissertation date: May 25th 2016 © Copyright Juliane Wissuwa The material in this publication is protected by copyright law. Year: 2016 Title: The Arctic Mid-Ocean Ridge Vent Fields – A valuable Resource for Marine Bioprospecting? Author: Juliane Wissuwa Print: AiT Bjerch AS / University of Bergen ŝŝŝ Contents Scientific environment .............................................................................................................. v Acknowledgements .................................................................................................................. vi Abstract .................................................................................................................................. viii Abbreviations ............................................................................................................................ x List of Publications .................................................................................................................. xi 1. Introduction ....................................................................................................................... 1 1.1 Background ................................................................................................................ 1 1.2 Enzymes from extremophiles and their biotechnological application ......................
    [Show full text]
  • Inositol (Powder) Introduced 2008
    Product Information Sheet – March 2016 Inositol (powder) Introduced 2008 What Is It? Inositol (powder) Inositol is a component of the B-complex family. It supports healthy two scoops (approximately 4.2 g) contain v central nervous system function, including emotional wellness, healthy mood and behavior. Additionally, it may promote ovarian health.* inositol (as myo-inositol) .................................................................................4.2 g serving size: approximately 4.2 g (2 scoops) Uses For Inositol (powder) servings per container: 60 Emotional Wellness: Myo-inositol is the primary form of inositol 2 scoops, 1–2 times daily, with or between meals, or as directed found in the central nervous system. It plays an important role in cell by a health professional. membrane formation and serves as part of the phosphatidylinositol second messenger system, supporting serotonin, norepinenephrine and cholinergic receptor function. As a result, inositol may support healthy mood, emotional wellness and behavior, and ease occasional nervous tension.* Ovarian Function: Research suggests that myo-inositol may help to support healthy ovulatory activity, ovarian function and reproductive system function.* What Is The Source? Myo-inositol is derived from rice bran. Recommendations Pure Encapsulations® recommends 2 scoops, 1–2 times daily, with or between meals, or as directed by a health professional. Are There Any Potential Side Effects Or Precautions? Rarely, inositol has been associated with nausea, fatigue, headache or dizziness. If pregnant or lactating, consult your physician before taking this product. Are There Any Potential Drug Interactions? At this time, there are no known adverse reactions when taken in conjunction with medications. Consult your physician for more information. *These statements have not been evaluated by the Food and Drug Administration.
    [Show full text]
  • WO 2015/072852 Al 21 May 2015 (21.05.2015) P O P C T
    (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date WO 2015/072852 Al 21 May 2015 (21.05.2015) P O P C T (51) International Patent Classification: (81) Designated States (unless otherwise indicated, for every A61K 36/84 (2006.01) A61K 31/5513 (2006.01) kind of national protection available): AE, AG, AL, AM, A61K 31/045 (2006.01) A61P 31/22 (2006.01) AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, A61K 31/522 (2006.01) A61K 45/06 (2006.01) BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, (21) International Application Number: HN, HR, HU, ID, IL, IN, IR, IS, JP, KE, KG, KN, KP, KR, PCT/NL20 14/050780 KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG, (22) International Filing Date: MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, 13 November 2014 (13.1 1.2014) PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, (25) Filing Language: English TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (26) Publication Language: English (84) Designated States (unless otherwise indicated, for every (30) Priority Data: kind of regional protection available): ARIPO (BW, GH, 61/903,430 13 November 2013 (13. 11.2013) US GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, TZ, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, (71) Applicant: RJG DEVELOPMENTS B.V.
    [Show full text]
  • Synthesis of Mannosylglucosaminylinositol
    Proc. Nati. Acad. Sci. USA Vol. 89, pp. 6025-6029, July 1992 Medical Sciences Synthesis of mannosylglucosaminylinositol phospholipids in normal but not paroxysmal nocturnal hemoglobinuria cells (complement/decay-accelerating factor/CD59) SHINICHI HIROSE*, LAKSHMESWARI RAVI*, GREGORY M. PRINCE*, MELVIN G. ROSENFELDt, ROBERT SILBERf, STEVEN W. ANDRESEN§, SANDRA V. HAZRA¶, AND M. EDWARD MEDOF*II *Institute of Pathology, Case Western Reserve University, Cleveland, OH 44106; Departments of tCell Biology and *Medicine, New York University Medical Center, New York, NY 10016; §Cleveland Clinic Foundation, Cleveland, OH 44106; and lAkron General Medical Center, Akron, OH 44307 Communicated by Frederick C. Robbins, November 29, 1991 (received for review September 12, 1991) ABSTRACT To identify mannosyl (Man)-containing inter- have been identified, information concerning the biochemical mediates ofthe human glycoinositol phospholipid (GPI) anchor pathway(s) responsible for their intracellular GPI-anchor pathway and examine their expression in paroxysmal nocturnal assembly and protein incorporation is only beginning to hemoglobinuria (PNH), mannolipid products deriving from in emerge. vitro guanosine diphosphate [3HJMan labeling of HeLa cell Among human GPI-anchored proteins are the decay- microsomes were characterized. The defined GPI species were accelerating factor (DAF) and CD59, membrane-associated correlated with products deriving from in vivo [3HJMan label- regulators of the complement cascade which protect host ing of normal and (GPI-anchor defective) affected leukocytes. tissues from autologous complement attack (reviewed in refs. In vitro analyses in HeLa cells showed dolichol-phosphoryl 2-4). Deficient expression of these proteins underlies an (Dol-P)-[3H]Man and a spectrum of [3H]Man lipids exhibiting acquired hemolytic disorder termed paroxysmal nocturnal TLC mobilities approximating those of Trypanosoma brucei hemoglobinuria (PNH), and the lesion responsible for the (Tryp) GPI precursors.
    [Show full text]
  • Ion Channels
    UC Davis UC Davis Previously Published Works Title THE CONCISE GUIDE TO PHARMACOLOGY 2019/20: Ion channels. Permalink https://escholarship.org/uc/item/1442g5hg Journal British journal of pharmacology, 176 Suppl 1(S1) ISSN 0007-1188 Authors Alexander, Stephen PH Mathie, Alistair Peters, John A et al. Publication Date 2019-12-01 DOI 10.1111/bph.14749 License https://creativecommons.org/licenses/by/4.0/ 4.0 Peer reviewed eScholarship.org Powered by the California Digital Library University of California S.P.H. Alexander et al. The Concise Guide to PHARMACOLOGY 2019/20: Ion channels. British Journal of Pharmacology (2019) 176, S142–S228 THE CONCISE GUIDE TO PHARMACOLOGY 2019/20: Ion channels Stephen PH Alexander1 , Alistair Mathie2 ,JohnAPeters3 , Emma L Veale2 , Jörg Striessnig4 , Eamonn Kelly5, Jane F Armstrong6 , Elena Faccenda6 ,SimonDHarding6 ,AdamJPawson6 , Joanna L Sharman6 , Christopher Southan6 , Jamie A Davies6 and CGTP Collaborators 1School of Life Sciences, University of Nottingham Medical School, Nottingham, NG7 2UH, UK 2Medway School of Pharmacy, The Universities of Greenwich and Kent at Medway, Anson Building, Central Avenue, Chatham Maritime, Chatham, Kent, ME4 4TB, UK 3Neuroscience Division, Medical Education Institute, Ninewells Hospital and Medical School, University of Dundee, Dundee, DD1 9SY, UK 4Pharmacology and Toxicology, Institute of Pharmacy, University of Innsbruck, A-6020 Innsbruck, Austria 5School of Physiology, Pharmacology and Neuroscience, University of Bristol, Bristol, BS8 1TD, UK 6Centre for Discovery Brain Science, University of Edinburgh, Edinburgh, EH8 9XD, UK Abstract The Concise Guide to PHARMACOLOGY 2019/20 is the fourth in this series of biennial publications. The Concise Guide provides concise overviews of the key properties of nearly 1800 human drug targets with an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties.
    [Show full text]
  • Inhibition of Vessel Permeability by TNP-470 and Its Polymer Conjugate, Caplostatin
    ARTICLE Inhibition of vessel permeability by TNP-470 and its polymer conjugate, caplostatin Ronit Satchi-Fainaro,1 Roni Mamluk,1 Ling Wang,3 Sarah M. Short,1 Janice A. Nagy,2 Dian Feng,2 Ann M. Dvorak,2 Harold F. Dvorak,2 Mark Puder,1 Debabrata Mukhopadhyay,2,3 and Judah Folkman1,* 1Children’s Hospital Boston and Harvard Medical School, Vascular Biology Program, Department of Surgery, 1 Blackfan Circle, Karp Family Research Laboratories, Floor 12, Boston, Massachusetts 02115 2 Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215 3 Biochemistry and Molecular Biology and Mayo Cancer Center, Mayo Clinic, Rochester, Minnesota 55905 *Correspondence: [email protected] Summary Angiogenesis inhibitors, such as TNP-470 and the nontoxic HPMA copolymer-TNP-470 (caplostatin), are emerging as a class of anticancer drugs. We report that TNP-470 and caplostatin inhibit vascular hyperpermeability of tumor blood vessels as well as that induced in mouse skin by different mediators. Treatment with TNP-470 or angiostatin for 3 days was sufficient to reduce permeability of tumor blood vessels, delayed-type hypersensitivity, and pulmonary edema induced by IL-2. TNP-470 also inhibited VPF/VEGF-induced phosphorylation of VEGFR-2, calcium influx, and RhoA activation in endothelial cells. These results identify an activity of TNP-470, that of inhibiting vessel hyperpermeability. This activity likely contributes to TNP-470’s antiangiogenic effect and suggests that caplostatin can be used in the treatment of cancer and inflammation. Introduction vival, and permeability) by activating VEGFR-2 (Claesson- Welsh, 2003). Angiogenesis, the generation of new blood vessels from preex- While EC proliferation is an important component of angio- isting microvasculature (Folkman and Kalluri, 2003), is regu- genesis (Koch et al., 1994), VPF/VEGF has relatively weak mi- lated by a number of different growth factors (Matsumoto and togenic activity compared to other factors such as basic fibro- Claesson-Welsh, 2001).
    [Show full text]
  • WO 2015/072853 Al 21 May 2015 (21.05.2015) P O P C T
    (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date WO 2015/072853 Al 21 May 2015 (21.05.2015) P O P C T (51) International Patent Classification: (81) Designated States (unless otherwise indicated, for every A61K 45/06 (2006.01) A61K 31/5513 (2006.01) kind of national protection available): AE, AG, AL, AM, A61K 31/045 (2006.01) A61K 31/5517 (2006.01) AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, A61K 31/522 (2006.01) A61P 31/22 (2006.01) BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, A61K 31/551 (2006.01) DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IR, IS, JP, KE, KG, KN, KP, KR, (21) International Application Number: KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG, PCT/NL20 14/050781 MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, (22) International Filing Date: PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, SC, 13 November 2014 (13.1 1.2014) SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (25) Filing Language: English (84) Designated States (unless otherwise indicated, for every (26) Publication Language: English kind of regional protection available): ARIPO (BW, GH, (30) Priority Data: GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, 61/903,433 13 November 2013 (13.
    [Show full text]