DOCSLIB.ORG

Download PDF (489K)

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Download PDF (489K) 296 Proc. Jpn. Acad., Ser. B 83 (2007) [Vol. 83, Review Physiology and pathophysiology of prostanoid receptors By Shuh NARUMIYAÃ1,Ã2;y (Communicated by Tasuku HONJO, M.J.A.) Abstract: Prostanoids, consisting of prostaglandins (PGs) and thromboxanes (TXs), are oxygenated products of C20 unsaturated fatty acids. They include PGD2,PGE2,PGF2 ,PGI2, and TXA2. Given that aspirin-like nonsteroidal anti-inflammatory drugs exert their actions by suppressing prostanoid production, prostanoids have been implicated in processes inhibited by these drugs, including inflammation, fever, and pain. Prostanoids also contribute to vascular homeostasis, reproduction, and regulation of kidney and gastrointestinal functions. How prostanoids exert such a variety of actions had remained unclear, however. Prostanoids are released outside of cells immediately after their synthesis and exert their actions by binding to receptors on target cells. We have identified a family of eight types or subtypes of G protein– coupled receptors that mediate prostanoid actions. Another G protein–coupled receptor was also identified as an additional receptor for PGD2. Genes for these receptors have been individually disrupted in mice, and analyses of these knockoutmicehavenotonlyelucidatedthemolecular and cellular mechanisms of known prostanoid actions but also revealed previously unknown actions. In this article, I review the physiological and pathophysiological roles of prostanoids and their receptors revealed by these studies. Keywords: prostaglandin, thromboxane, cyclooxygenase, G protein–coupled receptor Prostanoids, consisting of prostaglandins the 5-cis, 13-trans, and 17-cis double bonds, re- (PGs) and thromboxanes (TXs), are oxygenated spectively. Given that arachidonic acid is the most products derived from C20 unsaturated fatty acids abundant among these precursor fatty acids in most (Fig. 1). -Homolinolenic acid, arachidonic acid, mammals, including humans, the series 2 prosta- and 5,8,11,14,17-eicosapentaenoic acid are the noids predominate in these organisms. These pre- precursor fatty acids for the series 1, 2, and 3 cursor fatty acids are esterified to the sn-2 position prostanoids, which contain the 13-trans double of glycerophospholipids in cell membranes and are bond, the 5-cis and 13-trans double bonds, and liberated from the membrane phospholipids by the action of phospholipase A2 in response to various 1) Ã1 Department of Pharmacology, Kyoto University Faculty physiological or pathological stimuli. Arachidonic of Medicine, Kyoto, Japan. acid thus liberated is metabolized by the action of Ã2 Recipient of the Imperial Prize and the Japan Academy cyclooxygenase (COX) to PGH ,whichisthen Prize in 2006. 2 y Department of Pharmacology, Kyoto University Faculty converted to various PGs by the respective PG of Medicine, Yoshida, Sakyo-ku, Kyoto 606-8501, Japan (e-mail: synthases (Fig. 1). There are two isoforms of COX; [email protected]). one is COX-1 that is constitutively expressed in Abbreviations: PG: prostaglandin; TX: thromboxane; COX: cyclooxygenase; NSAID: nonsteroidal anti-inflammatory many tissues, and the other is COX-2, expression of drug; GPCR: G protein–coupled receptor; cAMP: cyclic adeno- which is induced by various inflammatory as well as sine monophosphate; Th: T helper; ACTH: adrenocorticotropic other stimuli and suppressed by glucocorticoids hormone; LPS: lipopolysaccharide; IL: interleukin; TNF: tumor 2) necrosis factor; CRF: corticotropin-releasing factor; DRG: dorsal such as dexamethasone. Similarly, there are two root ganglion; Ig: immunoglobulin; OVA: ovalbumin; SNP: major isoforms of PGE synthase, cytosolic PGE single nucleotide polymorphism; DNFB: dinitrofluorobenzene; synthase (cPGES) that is constitutively expressed IBD: inflammatory bowel disease; DSS: dextran sodium sulfate; PTH: parathyroid hormone; RANKL: receptor activator of and membrane-bound PGE synthase-1 (mPGES-1) NF-B ligand. that, like COX-2, is induced by various proinflam- doi: 10.2183/pjab/83.296 #2007 The Japan Academy Nos. 9–10] Physiology and pathophysiology of prostanoid receptors 297 COOH Arachidonic acid Cyclooxygenase 2O2 7 4 2 O 9 8 6 5 3 COOH 10 14 1516 18 20 O 11 12 13 17 19 OOH PGG2 COOH PGI synthase TX synthase O COOH COOH O O O O OH OH OH PGH2 TXA2 OH PGD synthase PGF synthase PGI2 PGE synthase OH OH O COOH COOH COOH O OH OH OH OH OH PGD 2 PGE2 PGF2 α Fig. 1. Pathway of prostanoid biosynthesis. Arachidonic acid is metabolized by the action of cyclooxygenase (COX) first to prostaglandin endoperoxide (PGG2) and then to PGH2, which is subsequently converted to various PGs and TXA2 by respective synthases. Aspirin-like nonsteroidal anti-inflammatory drugs (NSAIDs) exert their effects by inhibiting COX and thereby suppressing prostanoid biosynthesis. matory stimuli and suppressed by glucocorticoids.3) they exert central actions such as induction of fever Prostanoids thus formed are released outside of or sleep. They regulate secretion and motility in cells immediately after their synthesis. PGH2, the gastrointestinal tract as well as transport of PGI2,andTXA2 are chemically unstable and are ions and water in the kidney. They play roles in degraded to inactive products under physiological apoptosis, cell differentiation, and oncogenesis. conditions, with half-lives of 30 s to a few minutes. They also regulate the activity of blood platelets Other PGs, although chemically stable, are metab- both positively and negatively, and they contribute olized rapidly. For example, they are inactivated to vascular homeostasis and hemostasis. Prosta- during a single passage through the lung. Prosta- noids thus exert a wide variety of actions in various noids are therefore thought to act locally, in the cells and tissues and the body. However, the vicinity of the site of their production. mechanisms underlying such actions remained a Aspirin-like nonsteroidal anti-inflammatory mystery until the receptors responsible were iden- drugs (NSAIDs) exert their pharmacological ac- tified, their cDNAs cloned, and their roles analyzed. tions by inhibiting COX and suppressing prosta- Furthermore, whereas methods for the chemical noid production. The actions of prostanoids have synthesis of natural prostanoids and related com- therefore been examined either by the addition of pounds have been developed for reproduction of or exogenous prostanoids to cells, tissues, or the body interference with the various bioactivities of pros- or by analysis of the effects of aspirin-like drugs on tanoids, they have been of limited use without various physiological or pathophysiological proc- knowledge of the prostanoid receptors and their esses. The typical actions of prostanoids revealed by properties. these studies include induction of the relaxation or contraction of various types of smooth muscle. Structure, signal transduction mechanisms, anddistributionofprostanoidreceptors Prostanoids also modulate neuronal activity by inhibiting or stimulating neurotransmitter release Given that prostanoids are produced from fatty or sensitizing sensory fibers to noxious stimuli, and acids and were therefore generally regarded as 298 S. NARUMIYA [Vol. 83, hydrophobic compounds, it was initially thought 29 amino acids, respectively, that do not share any that they were incorporated into the cell membrane structural motifs or hydrophobic features.13)–15) and exerted their actions by perturbing lipid fluid- These isoforms show similar ligand binding charac- ity. However, prostanoids are not as hydrophobic as teristics but distinct signal transduction properties, originally thought and do not incorporate into or as described below. Such multiple splice isoforms permeate the cell membrane.4) Furthermore, com- for EP3 have also been identified in other species parison of the potencies of various prostanoids as including rat, rabbit, cow, and human.11) In addi- determined by bioassays in various tissues revealed tion to this family of prostanoid receptors, there is a 16) that each prostanoid possesses a unique activity distinct type of receptor for PGD2. This receptor, profile, indicating that each compound has a designated CRTH2, was originally cloned as an specific site of action. Moreover, various synthetic orphan receptor expressed in T helper (Th) 2 TXA2 agonists and antagonists were developed in lymphocytes and has recently been shown to bind the late 1970s to early 80s, and these compounds PGD2 with an affinity as high as that of DP, facilitated the pharmacological characterization of although its binding profile for other PGD analogs 5) a receptor for TXA2. Biochemical evidence also differs from that of DP. CRTH2 belongs to the supported the existence of prostanoid receptors. family of chemokine receptors and mediates chemo- Beginning in the mid-1960s, the actions of prosta- taxisofTh2lymphocytesaswellasofeosinophils noids were repeatedly found to be associated with and basophils toward PGD2. changes in the levels of intracellular second mes- Signal transduction pathways linked to pros- sengers such as cyclic adenosine monophosphate tanoid receptors have been studied by examination (cAMP), phosphoinositides, and Ca2þ. In addition, of the effects of agonists on the intracellular the availability of radioisotopically labeled prosta- concentrations of second messengers such as cAMP, noid derivatives in the early 1970s allowed the Ca2þ, and inositol phosphates in cells transfected demonstration that many tissues and cells possess with expression vectors for each receptor. These specific high-affinity binding sites for
Load more

Recommended publications
  • 9-Deoxy-A9,A12-13,14
    Proc. Natl. Acad. Sci. USA Vol. 81, pp. 1317-1321, March 1984 Biochemistry 9-Deoxy-A9,A12-13,14-dihydroprostaglandin D2, a metabolite of prostaglandin D2 formed in human plasma (dehydration product of prostaglandin D2/serum albumin/cell growth inhibition) YOSHIHARU KIKAWA*, SHUH NARUMIYA*, MASANORI FUKUSHIMAt, HIROHISA WAKATSUKAt, AND OSAMU HAYAISHI§ *Department of Medical Chemistry, Kyoto University Faculty of Medicine, Sakyo-ku, Kyoto 606, Japan; tDepartment of Internal Medicine and Laboratory of Chemotherapy, Aichi Cancer Center, Chikusa-ku, Nagoya 464, Japan; tResearch Institute, Ono Pharmaceutical Co., Shimamoto, Mishima, Osaka 618, Japan; and §Osaka Medical College, Daigaku-cho, Takatsuki, Osaka 569, Japan Contributed by Osamu Hayaishi, November 8, 1983 ABSTRACT Incubation of prostaglandin D2 (PGD2) with from Sigma. Dimethylisopropylsilyl (Me2iPrSi) imidazole human plasma yielded a product that has been identified as 9- and methoxyamine hydrochloride were from Tokyo Kasei deoxy-9,10-didehydro-12,13-cdidehydro-13,14-dihydro-PGD2 (Tokyo). Sep-pak silica and Sep-pak C18 cartridges were (9-deoxy-_9,9'2-13,14-dihydro-PGD2). The identification was from Waters Associates. Precoated silica gel plates [G60- based on mass spectrometry, UV spectrometry, mobilities and (F254)] with concentration zones and silica gel 60 for column retention time on TLC and HPLC, and NMR. The conversion chromatography were from Merck. Sephadex LH-20 was a of PGD2 to this product was dependent on the incubation time product of Pharmacia. Solvents used in the extraction of and the amount of plasma added to a reaction mixture and was PGD2 metabolites for identification were distilled before use. abolished by prior boiling.
    [Show full text]
  • Metabolic Tracing of NAD Precursors Using Strategically Labelled Isotopes of NMN
    A thesis submitted in fulfilment of the requirements for the degree of Doctor of Philosophy Metabolic tracing of NAD+ precursors using strategically labelled isotopes of NMN by Lynn-Jee Kim Supervisors Dr. Lindsay E. Wu (Primary) Prof. David A. Sinclair (Joint-Primary) Dr. Lake-Ee Quek (Co-supervisor) School of Medical Sciences Faculty of Medicine Thesis/Dissertation Sheet Surname/Family Name: Kim Given Name/s: Lynn-Jee Abbreviation for degree as give in PhD the University calendar: Faculty: Faculty of Medicine School: School of Medical Sciences + Thesis Title: Metabolic tracing of NAD precursors using strategically labelled isotopes of NMN Abstract 350 words maximum: (PLEASE TYPE) Nicotinamide adenine dinucleotide (NAD+) is an important cofactor and substrate for hundreds of cellular processes involved in redox homeostasis, DNA damage repair and the stress response. NAD+ declines with biological ageing and in age-related diseases such as diabetes and strategies to restore intracellular NAD+ levels are emerging as a promising strategy to protect against metabolic dysfunction, treat age-related conditions and promote healthspan and longevity. One of the most effective ways to increase NAD+ is through pharmacological supplementation with NAD+ precursors such as nicotinamide mononucleotide (NMN) which can be orally delivered. Long term administration of NMN in mice mitigates age-related physiological decline and alleviates the pathophysiologies associated with a high fat diet- and age-induced diabetes. Despite such efforts, there are certain aspects of NMN metabolism that are poorly understood. In this thesis, the mechanisms involved in the utilisation and transport of orally administered NMN were investigated using strategically labelled isotopes of NMN and mass spectrometry.
    [Show full text]
  • Suppression of Poly(ADP-Ribose)
    Proc. Nati. Acad. Sci. USA Vol. 81, pp. 7132-7136, November 1984 Cell Biology Induction of murine teratocarcinoma cell differentiation by suppression of poly(ADP-ribose) synthesis (NADW/retinoic acid/3-aminobenzamide/immunofluorescence) YASUHIRO OHASHI*t, KUNIHIRO UEDA*t, OSAMU HAYAISHI*§, KouICHI IKAI¶, AND OTSURA NIWAII Departments of *Medical Chemistry, ¶Dermatology, and "Experimental Radiology, Kyoto University Faculty of Medicine, Yoshida, Sakyo-ku, Kyoto 606, Japan Contributed by Osamu Hayaishi, July 27, 1984 ABSTRACT Poly(ADP-ribose) synthesizing activity in present study, we report a marked decrease in nuclear po- mouse teratocarcinoma EC-Al cells decreased markedly dur- ly(ADP-ribose) synthesizing activity at a very early stage of ing differentiation induced by retinoic acid; the activities as- differentiation of teratocarcinoma cells induced by retinoic sayed in permeabilized cells decreased to 25% and 10% of the acid. Furthermore, we present evidence suggesting that ex- activity of control (uninduced cells) 2 and 3 days, respectively, ogenously added inhibitors of poly(ADP-ribose) synthetase after the addition of 0.1 ,uM retinoic acid to the culture medi- can induce the differentiation of these cells. um. This change preceded changes in morphology and DNA synthesis, which became prominent after 4 days. The decrease MATERIALS AND METHODS in poly(ADP-ribose) synthesizing activity appeared to be caused by a diminution of the synthetase protein and not by a Chemicals. [adenine-U-14C]NAD+ (266 Ci/mol; 1 Ci = 37 decrease in its catalytic activity, because the full activity dis- GBq) and [methyl-3H]dTTP (30 Ci/mmol) were purchased closed by DNase I treatment decreased in parallel, albeit at from Amersham.
    [Show full text]
  • Effects of 5-Hydroxykynurenamine, a New Serotonin Metabolite
    Proc. Nat. Acad. Sci. USA Vol. 71, No. 1, pp. 122-124, January 1974 Effects of 5-Hydroxykynurenamine, a New Serotonin Metabolite, on Isolated Dog Basilar Arteries (serotonin/amine/antagonist/artery) NOBORU TODA*, TAKASHI TOKUYAMAt, SIRO SENOHt, FUSAO HIRATA§, AND OSAMU HAYAISHI§ * Department of Pharmacology, and § Department of Medical Chemistry, Kyoto University Faculty of Medicine, Kyoto; t Department of Chemistry, Osaka City University Faculty of Science, Osaka; and $ Central Research Institute, Suntory Ltd., Osaka, Japan Contributed by Osamu Hayaishi, September 10, 1973 ABSTRACT Serotonin and 5-hydroxykynurenamine HK and serotonin were added directly to the bathing me- caused dose-related contractions in the spiral strips of dium in cumulative concentrations at the time when the dose- dog basilar arteries. The potency of 5-hydroxykynuren- amine was approximately 1/100 that of serotonin, the response curve was obtained. former frequently causing a transient relaxation preceding the contraction. The contractile responses to 5-hydroxy- RESULTS kynurenamine and serotonin were attenuated by methy- Serotonin in concentrations ranging from 10-9 to 10-5 M sergi(le. Treatment with 5-hydroxykynurenamine inhib- caused a dose-related increase in the tension of basilar arterial ited the response to serotonin, and this inhibitory effect was not completely reversed by removal of 5-hydroxy- strips (Fig. 1A). Contractile responses to serotonin were kvnurenamine from the bathing medium. The contractile reproducible five times when preparations were repeatedly response to K+ was only slightly attenuated by high con- washed and equilibrated in normal solutions for 40-60 min. centrations of 5-hydroxykynurenamine. It appears that 5-HEK (5 X 10-' to 5 X 10-5 M) caused slowly developing 5-hydroxykynurenamine and serotonin share receptors in contractions in a dose-dependent manner (Fig.
    [Show full text]
  • IUBMB Newsletter Issue 2.Pdf
    IUBMB NEWS Issue 2 October 2016 President’s Message IUBMB aims to promote research and education in In This Issue Biochemistry and Molecular Biology. In this regard, over the President’s Message years we have channelled great efforts into the research aspects of our science. We now consider it timely to turn our Report on the 16th IUBMB attention to educational initiatives. Conference / Young To address this aim and in collaboration with FEBS, we are organising a conference on Education in Biochemistry and Molecular Biology, to be held in Scientists’ Program Rehovot (Israel) in September 2017. The conference seeks to provide a think-tank Tang Prize Foundation setting in which to draw up ideas to improve the current approach to teaching these subjects, and to generate a series of recommendations to be shared with Awardees / IUBMB Travel the educational community. In this regard, this conference will serve to propel the Fellowships changes that are required to bring education in biochemistry and molecular biology st at all levels into the 21 century. Another Way to Think About Another important aspect of education is to provide young scientists from Disease by Gregory Petsko developing countries the opportunity to attend international congresses and meetings. IUBMB is firmly committed to this endeavour and devotes significant Retrospective — financial resources to this end. Given that the number of applications from African countries is very low, I wish to encourage our young African colleagues to apply Osamu Hayaishi and benefit from IUBMB travel awards and Wood-Whelan fellowships. An Appreciation — IUBMB is also launching a new activity, namely Focused Meetings.
    [Show full text]
  • From a Pseudomonad, Catalyzes the Oxygenation of L-Lysi an A,E
    Proc. Nat. Acad. Sci. USA Vol. 69, No. 12, pp. 3723-3726, December 1972 Alkylamine-Dependent Amino-Acid Oxidation by Lysine Monooxygenase- Fragmented Substrate of Oxygenase (Pseudomonas/enzyme/aminefamide/flavoprotein) SHOZO YAMAMOTO, TAKASHI YAMAUCHI, AND OSAMU HAYAISHI Department of Medical Chemistry, Kyoto University Faculty of Medicine, Kyoto, Japan Contributed by Osamu Hayaishi, October 10, 1972d ABSTRACT Lysine monooxygenase catalyzes the cIxy- a significant role in the catalysis of the enzyme. It would be of a rre- genative decarboxylation of L-lysine and produces coi heefoeto investigate the reaction of the enzyme sponding acid amide. L-Alanine was inactive as substriate. However, when propylamine was present, oxidation,Ibut in the presence of both a-monoamino acids and alkylamines- not oxygenation, of alanine was demonstrated with the of various carbon chain lengths-the two fragments of the oxygenase. Alanine was converted to pyruvate, with the normal substrate. liberation of ammonia and hydrogen peroxide, but proyI~yl- amine remained unchanged. Other a-monoamino accids MATERIALS AND METHODS were also oxidized in the presence of alkylamines wi various carbon chain lengths. The highest oxidase actiiV~it Lysine monooxygenase was purified and assayed as described was observed when the total chain length of both anm Lio (1). Pyruvate was determined with the aid of rabbit-muscle acid and amine was nearly identical with that of lysiine, lactate dehydrogenase Type II (Sigma) (4) or as its hydrazone Available evidence indicates that the amine-depend,lent (5). Oxygen consumption was followed by an oxygen electrode 5ine amino-acid oxidase activity is associated with the lys (1). As the solubility of oxygen in water decreases when the oxygenase activity.
    [Show full text]
  • Happy Holidays ASBMB Membersbayside Biomolecules
    SUBMIT YOUR LATE BREAKING MEETING ABSTRACTS BY FEB 25 January 2009 Happy Holidays ASBMB MembersBayside Biomolecules American Society for Biochemistry and Molecular Biology Edited by Ajit Varki, University of California, San Diego, Richard D. Cummings, Emory University School of Medicine, Atlanta, Jeffrey D. Esko, University of California, San Diego, Hudson H. Freeze, Burnham Institute for Medical Research, La Jolla, Pamela Stanley, Albert Einstein College of Medicine of Yeshiva University, New York, Carolyn R. Bertozzi, University of California, Berkeley, Gerald W. Hart, Johns Hopkins University of School of Medicine, Baltimore, and Marilynn E. Etzler, University of California, Davis he sugar chains of cells—known collectively as glycans—play a variety of impressive, critical, and often Tsurprising roles in biological systems. Glycobiology is the study of the roles of glycans in the growth and development, function, and survival of an organism. Glyco-related processes, described in vivid detail in the text, have become increasingly significant in many areas of basic research as well as biomedicine and biotechnology. This new edition of Essentials of Glycobiology covers the general principles and describes the structure and biosynthesis, diversity, and function of glycans and their relevance to both normal physiologic processes and human disease. Several new chapters present significant advances that have occurred since the publication of the first edition. Three sections of note describe organismal diversity, advances in our understanding of disease states and related therapeutic applications, and the genomic view of glycobiology. “Glycomics,” analogous to genomics and proteomics, is the systematic study of all glycan structures of a given cell type or organism and paves the way for a more thorough understanding of the functions of these ubiquitous molecules.
    [Show full text]
  • Physiology News
    PHYSIOLOGY NEWS summer 2009 I number 75 Calcium signalling insights from Sir Michael Berridge Physiology 2009 – back at UCD after an 18 year break Conference networking leads to post-doc position on a Japanese tropical island PowerLab : buy or rent Easy to use, easy to acquire PowerLab® Teaching Systems with LabTutor® and LabChart® soft ware have set the benchmarks in quality, ease-of-use, safety and fl exibility for over 20 years. Now, we’re proud to introduce another industry fi rst...the option to either buy or rent this powerful technology! Th e choice of purchase or rental options makes it even easier to get the world’s leading data acquisition system for Buy or Rent life science education. Our new Smart Rent Option off ers brand-new systems, low entry cost and free experiment soft ware upgrades. Talk to us to fi nd out more. Intuitive PowerLab Teaching Systems include experiments for human physiology, exercise physiology, pharmacology, Flexible Tool neurophysiology, psychophysiology, biology and more. Th e fl exibility of PowerLab systems adds to their cost- eff ectiveness – for purchasers and renters. Choose from over 100 experiments and 400 exercises More for introductory through to advanced levels. You can select the software for your courses and use authoring tools to modify/create experiments. Choose from over Experiments 20 Teaching Systems or let us create a customised solution. Contact us for an obligation-free demonstration. Tel: 01865 891 623 Email: [email protected] Web: www.adinstruments.com/buy_rent EQUIPMENT CERTIFIED FOR HUMAN CONNECTION UK • GERMANY • USA • BRAZIL • CHILE • INDIA • JAPAN • CHINA • MALAYSIA • NEW ZEALAND • AUSTRALIA CELEBRATING OVER 20 YEARS OF INNOVATIONS ADI_InstStudent_UK_PhysioNews.indd 1 15/5/09 2:32:20 PM PHYSIOLOGY NEWS Editorial 3 Meetings The Society’s dog.
    [Show full text]
  • Thomas Cech CV
    CURRICULUM VITAE Thomas R. Cech Education and Training B.A. in Chemistry, Grinnell College, Grinnell, Iowa 1970 Ph.D. in Chemistry, University of California, Berkeley with Prof. John E. Hearst 1975 Postdoctoral Fellow, Dept. of Biology, Massachusetts Institute of Technology with Prof. Mary Lou Pardue 1975-77 Positions University of Colorado Boulder Assistant Professor of Chemistry 1978-82 Associate Professor of Chemistry 1982-83 Professor of Chemistry and Biochemistry 1983- Professor of Molecular, Cellular and Developmental Biology (joint appointment) 1983- American Cancer Society Professor 1987- University of Colorado Anschutz Medical Campus Professor of Biochemistry and Molecular Genetics Member, CU Cancer Center 1988- Investigator, Howard Hughes Medical Institute 1988-99; 2009- University of Colorado Distinguished Professor 1990- President, Howard Hughes Medical Institute 2000-09 Director, University of Colorado BioFrontiers Institute (formerly the 2009- Colorado Initiative in Molecular Biotechnology) Honors and Awards National Science Foundation Graduate Fellow 1970-75 Public Health Service Research Fellow, National Cancer Institute 1975-77 Research Career Development Award, National Cancer Institute 1980-85 Passano Foundation Young Scientist Award 1984 Harrison Howe Award 1984 Guggenheim Fellow 1985-86 Pfizer Award in Enzyme Chemistry 1985 Esquire Magazine Register 1985 Denver Post Westerner of the Year 1986 U. S. Steel Award in Molecular Biology 1987 Member, National Academy of Sciences 1987 Honorary Degree, Doctor of Science, Grinnell College 1987 V. D. Mattia Award 1987 Member, American Academy of Arts and Sciences 1988 Newcombe-Cleveland Award, AAAS (with Arthur J. Zaug) 1988 Heineken Prize, Royal Netherlands Academy of Sciences 1988 Gairdner Foundation International Award 1988 Louisa Gross Horwitz Prize (with Phillip A.
    [Show full text]
  • Lessons from Translational Research on the Natriuretic Peptide Family and Leptin —
    538 Proc. Jpn. Acad., Ser. B 95 (2019) [Vol. 95, Review Translational science: Newly emerging science in biology and medicine — Lessons from translational research on the natriuretic peptide family and leptin — † By Kazuwa NAKAO*1, (Edited by Hiroo IMURA, M.J.A.) Abstract: Translation is the process of turning observations in the laboratory, clinic, and community into interventions that improve the health of individuals and the public, ranging from diagnostics and therapeutics to medical procedures and behavioral changes. Translational research is defined as the effort to traverse a particular step of the translation process for a particular target or disease. Translational science is a newly emerging science, distinct from basic and clinical sciences in biology and medicine, and is a field of investigation focused on understanding the scientific and operational principles underlying each step of the translational process. Advances in translational science will increase the efficacy and safety of translational research in all diagnostic and therapeutic areas. This report examines translational research on novel hormones, the natriuretic peptide family and leptin, which have achieved clinical applications or for which studies are still ongoing, and also emphasizes the lessons that translational science has learned from more than 30 years’ experience in translational research. Keywords: translational science, translational research, natriuretic peptide family (ANP, BNP, CNP), leptin, animal disease model, rare disease The original definition of translation refers to 1. Introduction the process of turning observations in the laboratory, Linguistically, the term “translation” refers to clinic, and community into interventions that im- the conversion of one language to another language. prove the health of individuals and the public, The term is also used to refer to the synthesis of ranging from diagnostics and therapeutics to medical proteins from mRNA in biology.
    [Show full text]
  • The Physiologist
    A Publication of The American Physiological Society The EB ‘99 Late Breaking Abstracts Deadline:See February PhysiologistPage 415 22, 1999 Volume 41, Number 6 December 1998 Trends in Early Research Careers of Life Scientists Executive Summary The 50 years since the end of World War II The continued success of the life-science have seen unprecedented growth in the life sci- research enterprise depends on the uninterrupted ences. In 1997 US government investments in entry into the field of well-trained, skilled, and health research exceeded $14 billion, private motivated young people. For this critical flow to foundations contributed more than $1.2 billion, be guaranteed, young aspirants must see that and industry’s investment in health research and there are exciting challenges in life-science development exceeded $17 billion. Government research and they need to believe that they have and private support of agriculture and environ- a reasonable likelihood of becoming practicing Inside mental research approached $5 billion. Clearly, independent scientists after their long years of the life-science enterprise is large and vigorous. training to prepare for their careers. Yet recent The large investment in the life sciences has trends in employment opportunities suggest that produced many important results. Discoveries in the attractiveness to young people of careers in Bylaw Changes agricultural science have improved our under- life-science research is declining. Proposed by standing of soils and their chemistry and have In the last few years, reports from the Council led to the development of new strains of crop National Research Council have detailed a plants that are resistant to diseases and yield changing world for young scientists.
    [Show full text]
  • Stadtman, Earl 2001 D Dr
    Stadtman, Earl 2001 D Dr. Earl Stadtman Oral History 2001 D Download the PDF: Stadtman_Earl_Oral_History_2001_D (PDF 95 kB) Earl R. Stadtman, Ph.D. This is the fourth interview in a series on the career of Dr. Earl R. Stadtman. It was conducted on February 13, 2001, in his office on the second floor of Building 3, National Institutes of Health, Bethesda, Maryland. The interviewer is Dr. Buhm Soon Park. Park: First of all, thank you very much for having an oral history interview with me. We have already a series of interviews, but today I’d like to go back to your early childhood and your educational background in secondary schools and during university training, and possibly your graduate years at Berkeley, and probably we’d better stop at that time and move on to your postdoctoral years and NIH years next time. So today I want to focus on how you got interested in science, and especially biochemistry, and your family background and who was the most influential in your decision to be a scientist and things like that. So let me--let’s start with your background. Can you talk a little bit about your parents and, if possible, could you spell your... Stadtman: My parents were both farmers in Kansas, and my father went to the University of Oklahoma for one year, and then he signed up--he was taking a degree in engineering, and he signed up for a survey, to be part of a survey of the New Mexico territory. And he sort of fell in love with the New Mexico country, and he homesteaded there[1].
    [Show full text]