DOCSLIB.ORG

Ergocryptine, Estradiol, and Thyrotropin-Releasing Hormone

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Ergocryptine, Estradiol, and Thyrotropin-Releasing Hormone Changes of Cell Morphology and Prolactin Secretion Induced by 2-Br-«-Ergocryptine, Estradiol, and Thyrotropin-releasing Hormone in Rat Anterior Pituitary Cells in Culture Downloaded from http://rupress.org/jcb/article-pdf/86/2/377/1074283/377.pdf by guest on 26 September 2021 TONY ANTAKLY, GEORGES PELLETIER, FUSUN ZEYTINOGLU, and FERNAND LABRIE Medical Research Council Group in Molecular Endocrinology, Le Centre Hospitalier de l'Université Laval, Québec G1V 4G2, Canada . Dr. Antakly's present address is the Institute of Cancer Research, College of Physicians and Surgeons of Columbia University, New York, New York 10032. Dr. Zeytinoglu's present address is the Department of Toxicology, School of Public Health, Harvard University, Boston, Massachusetts 02115. ABSTRACT The secretion of prolactin in cultured pituitary cells was studied in correlation with the cellular changes induced by stimulatory or inhibitory agents . The techniques used in this study were: radioimmunoassay, immunocytochemistry, scanning (SEM) as well as transmission (TEM) electron microscopy. Prolactin secretion was stimulated by 17,8-estradiol (10 nM) as well as thyrotropin-releasing hormone (TRH) (3 nM) and inhibted by 2-Br-a-ergocryptine (CB-154) (1 ftM) . The total prolactin (release and cell content) increased between 2 and 8 d of estradiol treatment, indicating an increase of both synthesis and release of prolactin . This finding was in agreement with TEM observations because, in estradiol-treated prolactin cells, the Golgi saccules were distended and Golgi elements were increased, thus indicating increased synthetic activity of these cells. The addition of TRH over a 4-h period resulted in a significant degranulation of prolactin cells. In contrast, prolactin secretory granules became accumulated in the cells after CB-154 treatment for a period ranging from 4 to 24 h. In agreement, light microscope immunocytochemistry showed an increased reaction for prolactin after short-term (<24 h) incubation with CB-154. Because prolactin cells represent --70% of the glandular cell population as revealed by immunocytochemistry, it was then possible to observe the changes of cell surface by SEM. In most cells, estradiol and TRH led to an increase in the number and prominence of microvilli and blebs, whereas CB-154 treatment resulted in a slightly decreased number of microvilli and an increased occurrence of membrane foldings. This report thus provides morphological evidence for the stimulatory effects of estradiol and TRH, and the inhibitory effects of CB-154 on prolactin secretion in pituitary cells in primary culture. These data, moreover, show that acute changes in secretory activity of prolactin-secreting cells are accompanied by marked changes of their morphological characteristics. The secretion of prolactin in the anterior pituitary gland is ergot derivatives are potent inhibitors of prolactin secretion in under predominant inhibitory control by the hypothalamus vivo as well as in vitro (16, 26, 31, 33) . (30) . Recent data indicate that dopamine may be the main or The stimulatory influence of the hypothalamus can, at least even the only inhibitory substance of hypothalamic origin partly, be mediated by thyrotropin-releasing hormone (TRH). involved in the control of prolactin secretion (11, 29, 37) . This This tripeptide is known to stimulate prolactin secretion in role ofdopamine is also supported by the finding that 2-bromo- vivo (7, 14) and in vitro (15, 38) . Prolactin secretion is also well a-ergocryptine (CB-154), a potent dopamine agonist, and other known to be increased after estrogen treatment in man (10, 39) THE JOURNAL of CELL i31OLOGV " VOLUME 86 AueusT 1980 377-387 © The Rockefeller University Press " 0021-9525/80/08/0377/11 $1 .00 377 and the rat (13). Recently, estrogens have been found not only Na2CO3 with 2 mM EDTA was added to the Petri dishes. Subsequently, the Petri prolactin secretion but also to reverse the inhibitory dishes were rinsed with 1 ml of acidified DMEM, and the pooled suspensions to stimulate were frozen, thawed, centrifuged at 100 g for 7 min at 4°C, and the supernate effects of dopamine agonists (including CB-154) by a direct was stored at -20°C until assayed. action at the pituitary level (26, 34). Pituitary cells in primary culture (25, 38) offer an attractive Hormone Assays system for the study of cells by scanning electron microscopy and permit a precise correlation with changes of pituitary Prolactin was measured in duplicate by a double-antibody radioimmunoassay (15) using rat prolactin I-2 and rabbit antisera (anti-rat prolactin-S-3) kindly hormone secretion induced by various stimulatory or inhibitory supplied by Dr. A. F. Parlow fortheNational Instituteof Arthritis and Metabolic agents. In preliminary reports (1, 2), we have recently described Diseases, Rat Pituitary Hormone Program. Radioimmunoassay data were ana- a good correlation between the surface morphology of anterior lyzed with a Hewlett-Packard calculator (model 9830, Hewlett-Packard Co ., Palo pituitary cells in primary culture and prolactin and thyroid- Alto, Calif.) using a program based on model II of Rodbard and Lewald (35). The statistical significance was determined according to the multiple-range test stimulating hormone (TSH) secretion after short- and long- of Duncan-Kramer (24) . Alldata are presented as the means t SEM of duplicate term treatment with estrogens, CB-154, triiodothyronine, TRH, measurements of triplicate dishes. and colchicine (3). In the present report, we have used immu- nocytochemical localization of prolactin, scanning and trans- Immunocytochemistry mission electron microscopy, and radioimmunoassay data for each experimental condition, to describe the effects and inter- Petri dishes were rinsed four times with Tris-buffered saline (Tris, 0.05 M, actions of l7ß-estradiol (E2), TRH, and CB-154 in this system NaCl 0.9%, pH 7.6) and fixed in situ with Bouin's fixative for 20 h at 4°C or with 4% buffered paraformaldehyde as previously described (4). Cells were subse- at the cellular level. quently processed for the immunocytochemical localization of prolactin by the Downloaded from http://rupress.org/jcb/article-pdf/86/2/377/1074283/377.pdf by guest on 26 September 2021 unlabeled antibody method and the peroxidase-antiperoxidase complex tech- MATERIALS AND METHODS nique (PAP) according to Stemberger (36) and as previously described (4). The dilution of the rabbit anti-prolactin serum (same lot as that used in the hormone Materials assays) was 1/1,000-1/2,000. Diaminobenzidine (Sigma Chemical Co ., St . Louis, Mo.) (22) was used as hydrogen donor for the localization of peroxidase. The CB-154 was kindly provided by Sandoz Pharmaceuticals (East Hanover, N.J .) specificity of the immunocytochemical reaction was tested by incubating the cells whereas TRH and Ez were purchased from Peninsula Laboratories Inc. (San either with antisera previously absorbed with excess antigen or with sera from Carlos, Calif.) and Steraloids, Inc. (Pawling, N.Y .), respectively . Media and sera unimmunized rabbits. Finally, to eliminate the possibility that endogenous per- for tissue cultures were obtained from Grand Island Biological Co. (Grand oxidases might be participating in the reaction, cells from each experimental Island, N.Y .), and glutaraldehyde (special grade) was a product of Ladd Research group were simply processed directly for the localization of peroxidase without Industries, Inc. (Burlington, Vt.). incubation with the antisera. The staining of the nuclei in the same Petri dish was done by indirect Preparation of Dispersed Anterior Pituitary Cells immunotluorescence procedure using sera from patients containing antinuclear antibodies (17) (kindly provided by the Department of Immunology of Le Centre Adult female Sprague-Dawley rats weighing 200-400 g (obtained from Ca- Hospitalier de l'Universit6 de Laval) . Observations were performed with a Leitz nadian Breeding Farms, St . Constant, Quebec) at random stages of the estrous microscope suitable for fluorescence and phase-contrast microscopy . A given cycle were used for the preparation of primary cultures of anterior pituitary cells field was first observed for fluorescence using a mercury lamp source; the as previously described (25, 38). The dissociated cells (8.5-9.0 x 10) were plated fluorescing nuclei were counted (Fig. 3). Then, the mercury lamp source was in Coming Glass Works, Science Products Div. (Corning, N.Y.), polystyrene shut off using the built-in shutter, and a usual tungsten lamp light source was Petri dishes (35 x 10 mm) in 1.5 ml of Dulbecco's modified Eagle's medium used and the number of positive cells, stained dark brown by the peroxidase (DMEM) containing 2.5% fetal calf serum and 10% horse serum (dextran-coated localization reaction, wascounted. In some cases, the same field was also observed charcoal adsorbed, 25), nonessential amino acids, 50 U/ml penicillin, and 50 pg/ by phase-contrast microscopy . A total of -800 cells was counted in each Petri ml streptomycin . Cell counts were done (using a hemocytometer) during plating dish in not less than three Petri dishes for each group in most cases. to ensure that all the Petri dishes in an experiment were seeded with the same number of cells. The cells were maintained at 37°C in a water-saturated atmos- phere of 95% OZ and 5% C02 for up to 12 d. Scanning Electron Microscopy (SEM) Petri dishes that were removed from the 37°C incubator were quickly rinsed Determination of Cell Viability three times with 0.1 M cacodylate buffer containing 5% sucrose, pH 7.4, pre- warmed at 37°C before fixation in situ for l h at 37°C with 0.15 M Na-cacodylate For a cell culture to be representative of the whole population of a tissue, cell buffer containing 1% glutaraldehyde (390 mosmol, pH 7.4) also prewarmed at viability after dissociation must be high enough so that no major fraction of the 37°C . Petri dishes were subsequently rinsed with thecacodylate buffer, postfixed cells is excluded . The percent of viable cells in the dispersed cell suspension was with 1% OS04 in 0.1 M Na-cacodylate (pH 7.4), and then dehydrated with determined by the trypan blue method .
Load more

Recommended publications
  • Plant Protease Inhibitors: a Defense Strategy in Plants
    Biotechnology and Molecular Biology Review Vol. 2 (3), pp. 068-085, August 2007 Available online at http://www.academicjournals.org/BMBR ISSN 1538-2273 © 2007 Academic Journals Standard Review Plant protease inhibitors: a defense strategy in plants Huma Habib and Khalid Majid Fazili* Department of Biotechnology, The University of Kashmir, P/O Naseembagh, Hazratbal, Srinagar -190006, Jammu and Kashmir, India. Accepted 7 July, 2007 Proteases, though essentially indispensable to the maintenance and survival of their host organisms, can be potentially damaging when overexpressed or present in higher concentrations, and their activities need to be correctly regulated. An important means of regulation involves modulation of their activities through interaction with substances, mostly proteins, called protease inhibitors. Some insects and many of the phytopathogenic microorganisms secrete extracellular enzymes and, in particular, enzymes causing proteolytic digestion of proteins, which play important roles in pathogenesis. Plants, however, have also developed mechanisms to fight these pathogenic organisms. One important line of defense that plants have to fight these pathogens is through various inhibitors that act against these proteolytic enzymes. These inhibitors are thus active in endogenous as well as exogenous defense systems. Protease inhibitors active against different mechanistic classes of proteases have been classified into different families on the basis of significant sequence similarities and structural relationships. Specific protease inhibitors are currently being overexpressed in certain transgenic plants to protect them against invaders. The current knowledge about plant protease inhibitors, their structure and their role in plant defense is briefly reviewed. Key words: Proteases, enzymes, protease inhibitors, serpins, cystatins, pathogens, defense. Table of content 1.
    [Show full text]
  • Evidence for Two Different Modes of Tripeptide Disappearance in Human Intestine. Uptake by Peptide Carrier Systems and Hydrolysis by Peptide Hydrolases
    Evidence for two different modes of tripeptide disappearance in human intestine. Uptake by peptide carrier systems and hydrolysis by peptide hydrolases. S A Adibi, … , S S Masilamani, P M Amin J Clin Invest. 1975;56(6):1355-1363. https://doi.org/10.1172/JCI108215. Research Article The intestinal fate of two tripeptides (triglycine and trileucine), which differ markedly in solubility and molecular weight, have been investigated by jejunal perfusion in healthy human volunteers. Rates of glycine or leucine uptake from test solutions containing triglycine or trileucine were greater than from test solutions containing corresponding amounts of free glycine or free leucine, respectively. The rate of glycine uptake from a 100 mM triglycine solution was greater than that from a 150 mM diglycine solution. At each infused load of triglycine (e.g., 1,000 mumol/min) the rates (micromoles/minutes per 30 cm) of either triglycine disappearance (810 +/- 40) or glycine absorption (2,208 +/- 122) were markedly greater than the luminal accumulation rates of either diglycine (56 +/- 10) or free glycine (110 +/- 18). The luminal accumulation rate of free leucine during infusion of a 5 mM trileucine solution was over threefold greater than that of free glycine during the infusion of a 5 mM triglycine solution. Luminal fluid exhibited no hydrolytic activity against triglycine, but contained some activity against trileucine. Saturation of free amino acid carrier system with a large load of leucine did not affect glycine absorption rate from a triglycine test solution, but isoleucine markedly inhibited the uptake from a trileucine solution. When the carrier system for dipeptides was saturated with a large amount of glycylleucine, […] Find the latest version: https://jci.me/108215/pdf Evidence for Two Different Modes of Tripeptide Disappearance in Human Intestine UPTAKE BY PEPTIDE CARRIER SYSTEMS AND HYDROLYSIS BY PEPTIDE HYDROLASES SIAMAK A.
    [Show full text]
  • Safety Assessment of Tripeptide-1, Hexapeptide-12, and Related Amides As Used in Cosmetics
    Safety Assessment of Tripeptide-1, Hexapeptide-12, and Related Amides as Used in Cosmetics Status: Draft Report for Panel Review Release Date: February 21, 2014 Panel Meeting Date: March 17-18, 2014 The 2014 Cosmetic Ingredient Review Expert Panel members are: Chair, Wilma F. Bergfeld, M.D., F.A.C.P.; Donald V. Belsito, M.D.; Curtis D. Klaassen, Ph.D.; Daniel C. Liebler, Ph.D.; Ronald A Hill, Ph.D. James G. Marks, Jr., M.D.; Ronald C. Shank, Ph.D.; Thomas J. Slaga, Ph.D.; and Paul W. Snyder, D.V.M., Ph.D. The CIR Director is Lillian J. Gill, D.P.A. This report was prepared by Wilbur Johnson, Jr., M.S., Senior Scientific Analyst and Bart Heldreth, Ph.D., Chemist. © Cosmetic Ingredient Review 1620 L STREET, N.W., SUITE 1200 ◊ WASHINGTON, DC 20036-4702 ◊ PH 202.331.0651 ◊ FAX 202.331.0088 ◊ [email protected] Commitment & Credibility since 1976 Memorandum To: CIR Expert Panel Members and Liaisons From: Wilbur Johnson, Jr. Senior Scientific Analyst Date: February 21, 2014 Subject: Draft Report on Tripeptide-1, Hexapeptide-12, and Related Amides The draft report on palmitoyl oligopeptides was tabled at the March 18-19, 2013 CIR Expert Panel meeting, pending reorganization of the safety assessment. During the meeting, the Panel was provided with a letter from the CIR Science and Support Committee, recommending the creation of a new ingredient group consisting of ingredients for which the peptide sequence is known, namely, tripeptide -1, hexapeptide-12 and specific related amides. This has been done. Additionally, at the March meeting, further information was sought to better understand the extent and manner in which solid-phase peptide synthesis is used to create the peptide portion of ingredients included in the safety assessment.
    [Show full text]
  • TRH-Like Peptides
    Physiol. Res. 60: 207-215, 2011 https://doi.org/10.33549/physiolres.932075 REVIEW TRH-Like Peptides R. BÍLEK1, M. BIČÍKOVÁ1, L. ŠAFAŘÍK2 1Institute of Endocrinology, Prague, Czech Republic, 2Urology Clinic, Beroun, Czech Republic Received September 6, 2010 Accepted October 8, 2010 On-line November 29, 2010 Summary of the leaders working in the area concerning the TRH TRH-like peptides are characterized by substitution of basic research was Professor V. Schreiber from Prague, Czech amino acid histidine (related to authentic TRH) with neutral or Republic, which already in 1959 formulated the acidic amino acid, like glutamic acid, phenylalanine, glutamine, hypothesis that adenohypophyseal acid phosphatase is tyrosine, leucin, valin, aspartic acid and asparagine. The related to thyrotropin secretion and that TRH is its presence of extrahypothalamic TRH-like peptides was reported in possible activator (Schreiber and Kmentova 1959, peripheral tissues including gastrointestinal tract, placenta, neural Schreiber et al. 1962). TRH precursor, human prepro- tissues, male reproductive system and certain endocrine tissues. TRH, consists of 242 amino acid residues, and contains Work deals with the biological function of TRH-like peptides in six separate copies of the TRH progenitor sequence different parts of organisms where various mechanisms may (Satoh and Mori 1994), which determine the primary serve for realisation of biological function of TRH-like peptides as structure of TRH as a tripeptide pyroglutamyl-histidinyl- negative feedback to the pituitary exerted by the TRH-like proline amide. The transcriptional unit of prepro-TRH is peptides, the role of pEEPam such as fertilization-promoting localized on chromosome 3 in humans (three exons peptide, the mechanism influencing the proliferative ability of interrupted by two introns) (Yamada et al.
    [Show full text]
  • Ultraviolet Irradiation on a Pyrite Surface Improves Triglycine Adsorption
    life Article Ultraviolet Irradiation on a Pyrite Surface Improves Triglycine Adsorption Santos Galvez-Martinez and Eva Mateo-Marti * Centro de Astrobiología (CSIC-INTA), Ctra. Ajalvir, Km. 4, 28850 Torrejón de Ardoz, Spain; [email protected] * Correspondence: [email protected]; Tel.: + 34-915-872-973 Received: 27 July 2018; Accepted: 9 October 2018; Published: 25 October 2018 Abstract: We characterized the adsorption of triglycine molecules on a pyrite surface under several simulated environmental conditions by X-ray photoemission spectroscopy. The triglycine molecular adsorption on a pyrite surface under vacuum conditions (absence of oxygen) shows the presence of + two different states for the amine functional group (NH2 and NH3 ), therefore two chemical species (anionic and zwitterionic). On the other hand, molecular adsorption from a solution discriminates the NH2 as a unique molecular adsorption form, however, the amount adsorbed in this case is higher than under vacuum conditions. Furthermore, molecular adsorption on the mineral surface is even favored if the pyrite surface has been irradiated before the molecular adsorption occurs. Pyrite surface chemistry is highly sensitive to the chemical changes induced by UV irradiation, as XPS analysis shows the presence of Fe2O3 and Fe2SO4—like environments on the surface. Surface chemical changes induced by UV help to increase the probability of adsorption of molecular species and their subsequent concentration on the pyrite surface. Keywords: pyrite; triglycine; XPS; peptide; sulfide mineral; UV; surface; adsorption; prebiotic chemistry 1. Introduction Minerals can be very promising surfaces for studying biomolecule surface processes, which are of principal relevance in the origin of life and a source of chemical complexity [1,2].
    [Show full text]
  • Safety Assessment of Tripeptide-1, Hexapeptide-12, Their Metal Salts and Fatty Acyl Derivatives, and Palmitoyl Tetrapeptide-7 As Used in Cosmetics
    Safety Assessment of Tripeptide-1, Hexapeptide-12, their Metal Salts and Fatty Acyl Derivatives, and Palmitoyl Tetrapeptide-7 as Used in Cosmetics Status: Draft Final Report for Panel Review Release Date: May 16, 2014 Panel Meeting Date: June 9-10, 2014 The 2014 Cosmetic Ingredient Review Expert Panel members are: Chair, Wilma F. Bergfeld, M.D., F.A.C.P.; Donald V. Belsito, M.D.; Curtis D. Klaassen, Ph.D.; Daniel C. Liebler, Ph.D.; Ronald A Hill, Ph.D.; James G. Marks, Jr., M.D.; Ronald C. Shank, Ph.D.; Thomas J. Slaga, Ph.D.; and Paul W. Snyder, D.V.M., Ph.D. The CIR Director is Lillian J. Gill, D.P.A. This report was prepared by Wilbur Johnson, Jr., M.S., Senior Scientific Analyst and Bart Heldreth, Ph.D., Chemist. © Cosmetic Ingredient Review 1620 L STREET, N.W., SUITE 1200 ◊ WASHINGTON, DC 20036-4702 ◊ PH 202.331.0651 ◊ FAX 202.331.0088 ◊ [email protected] Commitment & Credibility since 1976 Memorandum To: CIR Expert Panel Members and Liaisons From: Wilbur Johnson, Jr. Senior Scientific Analyst Date: May 16, 2014 Subject: Draft Final Report on Tripeptide-1, Hexapeptide-12, their Metal Salts and Fatty Acyl Derivatives, and Palmitoyl Tetrapeptide-7 At the March 17-18, 2014 Expert Panel meeting, the Panel concluded that tripeptide-1, hexapeptide-12, their metal salts and fatty acyl derivatives, and palmitoyl tetrapeptide-7 are safe in the present practices of use and concentration and issued a tentative report. Comments and use concentration data received from the Council have been addressed/ incorporated. Included in this package for your review is the draft final report, the CIR report history, Literature search strategy, Ingredient Data profile, 2014 FDA VCRP data, Minutes from the March 2014 Panel Meeting, and comments (pcpc1pdf file) and use concentration data (data 1 file) received from the Council.
    [Show full text]
  • Peptides and How They Work with Kristina Kannada, Hydropeptide Fine Lines and Wrinkles Are the #1 Concern for Skin Care Consumers Chronological Vs
    Peptides And How They Work with Kristina Kannada, Hydropeptide Fine lines and wrinkles are the #1 concern for skin care consumers Chronological vs. Photoaging Factors Involved in Skin Aging Proteolic activity: Increase in degradation of proteins by cellular enzymes Free radical damage: Increase in unpaired electrons that accelerate aging Growth factors: Decrease in signaling molecules and cellular processes DEJ: Decrease in skin cohesion What happens with aging? 1: Thinning of the skin 2: Collagen fragmentation 3: Dermal epidermal junction (DEJ) flattening 4: Wrinkle formation Collagen and Aging Collagen gives skin structural support. It is the most abundant form of protein in the ECM, and its decrease is a major factor in wrinkle formation. 29 types of collagen have been identified. They are divided into five families according to type of structure: Fibrillar (Type I, II, III, V, XI), Facit (Type IX, XII, XIV), Short Chain (Type VIII, X), Basement Member (Type IV), and Other (Type VI, VII, XIII). Important types of collagen in terms of skin aging: • I: Most abundant form. Gives strength to the dermis. • III: Second most abundant form. Gives elasticity to the dermis. • IV: Major component of basement membrane. Forms a "chicken-wire" mesh with laminins and proteoglycans that influence cell adhesion, migration and differentiation. • V: Regulates the diameter of Collagen I and III fibers. • VI: A major component of microfibrils. Increases cell strength. • VII: Provides stability and anchors the dermis to the DEJ. • XVII: A transmembrane protein that is a structural component of hemidesmosomes, improving adhesion of the keratinocytes to the underlying membrane. A good skin care regimen must support multiple skin proteins for the best results.
    [Show full text]
  • The Amyloid-Beta Forming Tripeptide Cleavage Mechanism of G-Secretase David M Bolduc*, Daniel R Montagna, Matthew C Seghers, Michael S Wolfe*, Dennis J Selkoe*
    RESEARCH ARTICLE The amyloid-beta forming tripeptide cleavage mechanism of g-secretase David M Bolduc*, Daniel R Montagna, Matthew C Seghers, Michael S Wolfe*, Dennis J Selkoe* Ann Romney Center for Neurologic Diseases, Brigham and Women’s Hospital, Harvard Medical School, Boston, United States Abstract g-secretase is responsible for the proteolysis of amyloid precursor protein (APP) into short, aggregation-prone amyloid-beta (Ab) peptides, which are centrally implicated in the pathogenesis of Alzheimer’s disease (AD). Despite considerable interest in developing g-secretase targeting therapeutics for the treatment of AD, the precise mechanism by which g-secretase produces Ab has remained elusive. Herein, we demonstrate that g-secretase catalysis is driven by the stabilization of an enzyme-substrate scission complex via three distinct amino-acid-binding pockets in the enzyme’s active site, providing the mechanism by which g-secretase preferentially cleaves APP in three amino acid increments. Substrate occupancy of these three pockets occurs after initial substrate binding but precedes catalysis, suggesting a conformational change in substrate may be required for cleavage. We uncover and exploit substrate cleavage preferences dictated by these three pockets to investigate the mechanism by which familial Alzheimer’s disease mutations within APP increase the production of pathogenic Ab species. DOI: 10.7554/eLife.17578.001 *For correspondence: [email protected] (DMB); Introduction [email protected] Alzheimer’s disease (AD) is the most common form of dementia and currently the sixth leading cause (MSW); [email protected] of death in the United States, with no disease-modifying therapeutics available. A central and patho- (DJS) logical hallmark of AD is the deposition of amyloid-beta (Ab) plaques in the brain (Hardy and Sel- Competing interests: The koe, 2002).
    [Show full text]
  • A Peptide-Hormone-Inactivating Endopeptidase in Xenopus Laevis Skin Secretion
    Proc. Nati. Acad. Sci. USA Vol. 89, pp. 84-88, January 1992 Biochemistry A peptide-hormone-inactivating endopeptidase in Xenopus laevis skin secretion (metailoendopeptidase/neutral endopeptidase/thermolysin) KRISHNAMURTI DE MORAIS CARVALHO*, CARINE JOUDIOU, HAMADI BOUSSETTA, ANNE-MARIE LESENEY, AND PAUL COHEN Groupe de Neurobiochimie Cellulaire et Moldculaire de l'Universitd Pierre et Marie Curie, Unit6 de Recherche Associ6e 554 au Centre National de la Recherche Scientifique, % Boulevard Raspail, 75006 Paris, France Communicated by I. Robert Lehman, September 16, 1991 ABSTRACT An endopeptidase was isolated from Xenopus Indeed the Ser-Phe dipeptide, or a related motif such as laevis skin secretions. This enzyme, which has an apparent Phe-Phe, Ala-Phe, or His-Phe, is often present near the molecular mass of 100 kDa, performs a selective cleavage at the carboxyl terminus of substances from the bombesin and Xaa-Phe, Xaa-Leu, or Xaa-Ile bond (Xaa = Ser, Phe, Tyr, His, tachykinin families (1). Xaa-Phe, Xaa-Leu, or Xaa-Ile was or Gly) of a number of peptide hormones, including atrial also found frequently at a similar position in other peptide natriuretic factor, substance P, angiotensin H, bradykinin, hormone sequences of higher organisms, notably in atrial somatostatin, neuromedins B and C, and litorin. The peptidase natriuretic factor (ANF). exhibited optimal activity at pH 7.5 and aKm in the micromolar We have purified this enzyme 2029-fold and demonstrate range. No cleavage was produced in vasopressin, ocytocin, that it inactivates ANF by exclusive cleavage of the Ser25- minigastrin I, and [Leu5Jenkephalin, which include in their Phe26 bond and similarly inactivates a number of important sequence an Xaa-Phe, Xaa-Leu, or Xaa-Ile motif.
    [Show full text]
  • 18.4 Peptides 559
    18.4 Peptides 559 18.4Peptides AIMS: Tonome ond describethe bond thot linksomino ocids together.To drow completestructirol formulos for simple peptides.To controstthe biologicol functionsof some peptide hormones. A peptide is any combination of amino acids in which the alpha amino Focus group (-NH) of one acid is united with the alpha carboxylic group Amino acids are linked to form (-CO2H) of another through an amide bond. peptides. RO RO til ril H2N-C-C-OH + H-N-C-C-OH ------- I H HH Amino acid Amino acid RO RO til ttl H2N-C-C-N-C-C-OH + H2O ttt H HH Peptide The amide bonds formed in peptides always involve the alpha amino and alpha carboxylic acid groups and never those of side chains. More amino acids maybe added in the same fashion to form chains such as those in Figure l9.l. The amide bond between the carbonyl group of one amino acid and the nitrogen of the next amino acid in the peptide chain is called a peptide bond, or peptide link. Amino acids that haue been incorporated into peptides are called amino acid residues. As more amino acid residues are added, a backbone common to all peptide molecules is formed. The amino acid residue with a free amino group at one end of the chain is the N-termi- nal residue:the residue with a free carboxvlic acid at the other end of the chain is the C-terminal residue.The number of amino acid residuesin a peptide is often indicated by a set of preflxes for peptides of up to l0 C-terminal residue Figutel8.l Partsof a peptide-in this case,a tetrapeptide.The peptide bonds of the zigzagbackbone are shown in color.Note that the C-terminalis at the right and the N-terminqlis at the left.
    [Show full text]
  • Cosmetic Peptide Synthesis
    Cosmetic Peptide Synthesis Hair/Eyelash/Eyebrow Care Series Anti-Aging Prevent UV Damage Whitening Skin Renewal Slimming & Breast Enhancement Anti-Wrinkle Anti-allergic &Anti-Inflammatory Eye Care Cosmetic Peptides Bioactive Peptides have been widely used in cosmetics, which can be applied to anti-wrinkle, whitening, and skin regeneration areas. GenScript has more than 15 years of peptide synthesis experience and has provided high-quality peptides to over 10,000 customers worldwide. We are now offering cosmetic peptides synthesis service to fulfill your research needs in this area. Why choose GenScript? Skilled Technical Support Strict Quality Control Team of PhD Experts Batch-to-Batch Stability High Throughput Production Customizable Services to Meet Cost Effective and Fast Delivery Different Needs Categories Hair/Eyelash/Eyebrow Care Series Anti-Aging Prevent UV Damage Whitening Skin Renewal Slimming & Breast Enhancement Anti-Wrinkle Anti-allergic & Anti-Inflammatory Eye Care Hair/Eyelash/Eyebrow Care Series Product Activity Myristoyl Octapeptide-2 Promote hair growth Myristoyl Hexapeptide-16 Promote eyelash growth Myristoyl Tetrapeptide-12 Promote hair growth Myristoyl Pentapeptide-17 Promote eyelash and eyebrow growth Biotinoyl Tripeptide-1 Promote eyelash and eyebrow growth Acetyl Tetrapeptide-3 Promote eyelash and eyebrow growth Curcuminy1 Glutaryol Hexapeptide-24 Amide Promote eyelash and eyebrow growth Copper Tripeptide-1 Promote eyelash and eyebrow growth Copper Tripeptide-3 Promote eyelash and eyebrow growth Decapeptide-10 Promote
    [Show full text]
  • 24Amino Acids, Peptides, and Proteins
    WADEMC24_1153-1199hr.qxp 16-12-2008 14:15 Page 1153 CHAPTER COOϪ a -h eli AMINO ACIDS, x ϩ PEPTIDES, AND NH3 PROTEINS Proteins are the most abundant organic molecules 24-1 in animals, playing important roles in all aspects of cell structure and function. Proteins are biopolymers of Introduction 24A-amino acids, so named because the amino group is bonded to the a carbon atom, next to the carbonyl group. The physical and chemical properties of a protein are determined by its constituent amino acids. The individual amino acid subunits are joined by amide linkages called peptide bonds. Figure 24-1 shows the general structure of an a-amino acid and a protein. α carbon atom O H2N CH C OH α-amino group R side chain an α-amino acid O O O O O H2N CH C OH H2N CH C OH H2N CH C OH H2N CH C OH H2N CH C OH CH3 CH2OH H CH2SH CH(CH3)2 alanine serine glycine cysteine valine several individual amino acids peptide bonds O O O O O NH CH C NH CH C NH CH C NH CH C NH CH C CH3 CH2OH H CH2SH CH(CH3)2 a short section of a protein a FIGURE 24-1 Structure of a general protein and its constituent amino acids. The amino acids are joined by amide linkages called peptide bonds. 1153 WADEMC24_1153-1199hr.qxp 16-12-2008 14:15 Page 1154 1154 CHAPTER 24 Amino Acids, Peptides, and Proteins TABLE 24-1 Examples of Protein Functions Class of Protein Example Function of Example structural proteins collagen, keratin strengthen tendons, skin, hair, nails enzymes DNA polymerase replicates and repairs DNA transport proteins hemoglobin transports O2 to the cells contractile proteins actin, myosin cause contraction of muscles protective proteins antibodies complex with foreign proteins hormones insulin regulates glucose metabolism toxins snake venoms incapacitate prey Proteins have an amazing range of structural and catalytic properties as a result of their varying amino acid composition.
    [Show full text]