DOCSLIB.ORG

Activation of GABA Synthetic Enzyme, Glutamate Decarboxylase 67 By

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Activation of GABA Synthetic Enzyme, Glutamate Decarboxylase 67 By Impact Objectives • Gain a greater understanding of gamma amino butyric acid (GABA), the main inhibitory neurotransmitter in the mammalian central nervous system and the key to understanding the science behind the human taste bud • Develop a broad array of low-salt recipes for a range of dishes, which would enable the elderly and hospital patients to enjoy nutritional meals that also taste good • Ultimately work to commercialise a range of low-salt diet recipes The science of salt Dr Hiroshi Ueno is investigating GABA-synthesising enzyme and working on commercialising a low-salt diet recipe in research that is pleasing to the taste buds Could you begin was believed that GAD mainly locates in Our research is trying to achieve progress by describing how the brain and nervous system. A major in developing tasty low-salt dishes. We you came to work shift occurred in 1991 with the discovery still need to screen salt enhancers from in the field of of isoform for GAD, meaning humans thousands of spices and natural products. biochemistry? have two sets of GAD, namely GAD65 and We use an enzymatic tool that involves a GAD67, located in different chromosomes. spice extract with glutamate decarboxylase I studied quantum In addition, GAD65 is the target protein for 67 enzyme to measure enzymatic activity. If chemistry in Professor Kenichi Fukui’s self-immune disease of type I diabetes. the extract exhibits activation of the enzyme, laboratory at Kyoto University, Japan. We By using an immuno-histochemical method, it is a candidate salt enhancer. learned that chemistry explains detailed we found the localisation of GAD65 in the chemical reactions that can be immediately stomach, intestine and skin. Because of the Could you explain a little about the human applied to the mystery of life where our main limitations of the method, it was difficult taste tests you have conducted? energy sources are created by the chemical to find other locations. However, another reactions. At this point, my interests breakthrough came from transgenic mouse, Targeting young ladies at college level, shifted from chemistry to biochemistry. GAD67/GFP knock-in mouse, developed we test the tastes for miraculin and low Brandeis University in the US accepted my by Professors Kunihiko Obata and Yuchio salt bread, soup and some cooked foods. application to study at its graduate school. Yanagawa at the National Institute for Changing acidity (pH change) and acidic Brandeis offered a very strong biochemistry Physiological Sciences, Japan. In collaboration materials such as hydrochloric acid, citric programme, during which two eminent with Professors Obata and Yanagawa, with acid, acetic acid and other organic acids biochemists, W P Jencks and R H Abeles, Professor Masahito Watanabe at Osaka were compared for miraculin. For salt taught a one-year biochemistry course. At Medical College, Japan, and my PhD student effect, low salt food was compared with and that time I was interested in how coenzymes Yumi Nakamura, we found GAD67 localisation without small amounts of spice, as well as function. at type III taste buds. It is known that type III with the original recipe. taste buds express salt and acid receptors. Could you discuss your project ‘Search for It was also shown that GABA is produced in How do you see your research progressing salt-enhancement materials from natural the type III taste buds and GABA receptors in the next five to 10 years? resources by using GABA-synthesising are also expressed. GABA receptor is known enzyme, development of low-salt content as chloride ion channel, which participates in Looking ahead, we wish to commercialise foods, and study of salt signal transduction salt sensation. The discovery was the initial our low-salt diet recipe. We also hope to mechanism’? step as to why we started exploring the salt unearth new mechanisms of how salt mechanism. sensation travels from receptor to taste We first explored where GABA-synthesising nerve within the taste bud. enzyme, L-glutamate decarboxylase (GAD) What gaps in understanding is your locates in the body. Up until this point, it research trying to fill? www.impact.pub 71 Palatable research At Ryukoku University, Japan, researchers are exploring the science behind taste and working on low-salt dishes that can be enjoyed by the elderly and hospitalised patients There are five basic recognised tastes – Composition Data Base for Food’, and sweetness as well as umami. This effect is salty, sweet, bitter, sour and umami, and general biochemical approaches toward called “contrast effect.” If you control GABA taste receptors are distributed among two glutamate decarboxylase, histidine levels in the cell, it should affect umami different cell types, type II for sweet, bitter decarboxylase and serine carboxypeptidase taste. Low-salt food is often criticised due and umami, and type III for salty and sour. Y. He has a special interest in gamma to the loss of umami taste, which may be Combinations of these receptors contribute amino butyric acid (GABA), which is the prevented if we trick the contrast effect. to different perceptions of taste. Taste is main inhibitory neurotransmitter in the To do so, we add a small amount of spice clearly important, preparing the body for mammalian central nervous system. It when salt levels are reduced.’ digesting food by triggering the salivary is produced from L-glutamic acid in the glands and, ultimately, we want to eat food decarboxylation reaction catalysed by ACTIVATING GAD ACTIVITY that tastes good. However, nutrition is also glutamic acid decarboxylase (GAD). GABA In another line of investigation, the important. So how do we get the best of sends chemical messages through the brain researchers are exploring how to control both worlds and ensure the nutritional food and the nervous system and is involved in GAD activity by adding natural products we are consuming also tastes good? regulating communication between brain such as herbs and spices, as Ueno explains: cells. Due to the expected physiological ‘The purpose was to develop drugs to Dr Hiroshi Ueno is leading a project effect of GABA in the suppression of control the nerve system by using safe entitled ‘Activation of GABA synthetic blood pressure increase, diuretic effect materials, like the ones utilised in food.’ enzyme, glutamate decarboxylase, by spice and relaxation effect, it is also being used In this work, the researchers screened and reduction of salt and elucidation of in health food products. However, as the hundreds of herb and spice extracts testing salty taste signalling mechanism’. He is molecular role of GABA and GAD is not fully on GAD activity and observed whether each Professor in the Faculty of Agriculture at understood, Ueno and his team are seeking extract dramatically inhibited or activated Ryukoku University, Japan, with expertise to unravel these molecular mysteries. GAD enzymatic activity. According to Ueno, in applied microbiology and biochemistry. the results of the research represent the Prior to this, he held positions at Japan’s In the team’s project, ‘Search for salt- phenomena of eating. ‘For example, when Nara Women’s University, Kyoto University enhancement materials from natural we eat spicy food, we sweat or sometimes and Osaka Medical College, and Rockefeller resources by using GABA-synthesising have a bad stomach,’ he states. ‘It can be University in the US. His current research enzyme, development of low-salt content explained that food components could bind surrounds the science behind the taste foods, and study of salt signal transduction to specific receptors located in our digestive buds and has included projects such as mechanism’, the researchers began by systems, then those signals received by ‘Food Components Inhibiting Recombinant exploring where GAD locates in the body. the receptors are transmitted further to Human Histidine Decarboxylase Activity’, They used an immuno-histochemical cause various metabolic or physical activity ‘Construction of Free Amino Acids method and identified the localisation of changes. It is reasonable to understand GAD65 in the stomach, intestine and skin. the wide effects we observed for herbs and However, due to the limitations associated spices on GAD activity.’ with this method, the team was unable to identify further locations. Later, when the In this project, Ueno’s PhD student Kumiko team used a GAD67/GFP knock-in mouse, Hisaki and other members of the team the researchers were able to identify GAD67 examined spice extracts for possible salt localisation on type III taste buds, which are enhancer effects on human subjects. The known to express salt and acid receptors, team prepared breads in which the salt while the GABA receptor is known as the content was reduced by half the amount of chloride ion channel and to participate in the original recipe. They found that when salt sensation. Ueno provides an insight spice extract was used as a replacement for into the relationship between GABA and salt, the breads had a normal taste. This taste: ‘In the field of cookery, it is known prompted the team to work on developing GFP expressed on transgenic mouse taste bud that a small amount of salt enhances low-salt recipes for a range of dishes, 72 www.impact.pub Project Insights FUNDING Funding for this project provided through: JSPS KAKENHI Grant No. JP15K00872; The Salt Science Research Foundation, No. 16D1, 17D1, 18D1; Society for Research on Umami Taste; Japan Society for Bioscience, Biotechnology and Agrochemistry Innovative Research Program Award, 2010; and Urakami Foundation for Food and Food Culture Promotion. COLLABORATORS Dr Kumiko Hisaki, Osaka International College, Japan • Dr Yoko Nitta, Okayama Prefectural University, Japan • Dr H Komori, Kagawa University, Japan • Dr Yukiko Ueda, Osaka City University, Japan • Prof Emeritus Kunihiko Obata, National Institute for Physiological Sciences • Dr Yuchio Yanagawa, Gunma University, Japan • Dr Kenichi Ito, Ichimaru Pharcos Co., Ltd.
Load more

Recommended publications
  • The Baseline Structure of the Enteric Nervous System and Its Role in Parkinson’S Disease
    life Review The Baseline Structure of the Enteric Nervous System and Its Role in Parkinson’s Disease Gianfranco Natale 1,2,* , Larisa Ryskalin 1 , Gabriele Morucci 1 , Gloria Lazzeri 1, Alessandro Frati 3,4 and Francesco Fornai 1,4 1 Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56126 Pisa, Italy; [email protected] (L.R.); [email protected] (G.M.); [email protected] (G.L.); [email protected] (F.F.) 2 Museum of Human Anatomy “Filippo Civinini”, University of Pisa, 56126 Pisa, Italy 3 Neurosurgery Division, Human Neurosciences Department, Sapienza University of Rome, 00135 Rome, Italy; [email protected] 4 Istituto di Ricovero e Cura a Carattere Scientifico (I.R.C.C.S.) Neuromed, 86077 Pozzilli, Italy * Correspondence: [email protected] Abstract: The gastrointestinal (GI) tract is provided with a peculiar nervous network, known as the enteric nervous system (ENS), which is dedicated to the fine control of digestive functions. This forms a complex network, which includes several types of neurons, as well as glial cells. Despite extensive studies, a comprehensive classification of these neurons is still lacking. The complexity of ENS is magnified by a multiple control of the central nervous system, and bidirectional communication between various central nervous areas and the gut occurs. This lends substance to the complexity of the microbiota–gut–brain axis, which represents the network governing homeostasis through nervous, endocrine, immune, and metabolic pathways. The present manuscript is dedicated to Citation: Natale, G.; Ryskalin, L.; identifying various neuronal cytotypes belonging to ENS in baseline conditions.
    [Show full text]
  • Genetic Modulation of GABA Levels in the Anterior Cingulate Cortex by GAD1 and COMT
    Neuropsychopharmacology (2010) 35, 1708–1717 & 2010 Nature Publishing Group All rights reserved 0893-133X/10 $32.00 www.neuropsychopharmacology.org Genetic Modulation of GABA Levels in the Anterior Cingulate Cortex by GAD1 and COMT 1,2 1,2 3 1,2 Stefano Marenco* , Antonina A Savostyanova , Jan Willem van der Veen , Matthew Geramita , 1,2 1,2 1 1,2 1 Alexa Stern , Alan S Barnett , Bhaskar Kolachana , Eugenia Radulescu , Fengyu Zhang , 1 1 3 1 Joseph H Callicott , Richard E Straub , Jun Shen and Daniel R Weinberger 1 2 Clinical Brain Disorders Branch, GCAP, IRP, NIMH, Bethesda, MD, USA; Unit for Multimodal Imaging Genetics, Clinical Brain Disorders Branch, 3 GCAP, IRP, NIMH, Bethesda, MD, USA; Magnetic Resonance Spectroscopy Unit, MAP, IRP, NIMH, Bethesda, MD, USA g-Aminobutyric acid (GABA)-ergic transmission is critical for normal cortical function and is likely abnormal in a variety of neuropsychiatric disorders. We tested the in vivo effects of variations in two genes implicated in GABA function on GABA concentrations in prefrontal cortex of living subjects: glutamic acid decarboxylase 1 (GAD1), which encodes GAD67, and catechol-o-methyltransferase (COMT), which regulates synaptic dopamine in the cortex. We studied six single nucleotide polymorphisms (SNPs) in GAD1 previously associated with risk for schizophrenia or cognitive dysfunction and the val158met polymorphism in COMT in 116 healthy volunteers using proton magnetic resonance spectroscopy. Two of the GAD1 SNPs (rs1978340 (p ¼ 0.005) and rs769390 (p ¼ 0.004)) showed effects on GABA levels as did COMT val158met (p ¼ 0.04). We then tested three SNPs in GAD1 (rs1978340, rs11542313, and rs769390) for interaction with COMT val158met based on previous clinical results.
    [Show full text]
  • Identifying Genes in Monoamine Nuclei That May Determine Stress Vulnerability and Depressive Behavior in Wistar–Kyoto Rats
    Neuropsychopharmacology (2006) 31, 2449–2461 & 2006 Nature Publishing Group All rights reserved 0893-133X/06 $30.00 www.neuropsychopharmacology.org Identifying Genes in Monoamine Nuclei that may Determine Stress Vulnerability and Depressive Behavior in Wistar–Kyoto Rats 1 2 2 ,1 Kimberly A Pearson , Alisson Stephen , Sheryl G Beck and Rita J Valentino* 1Department of Pediatrics, The Children’s Hospital of Philadelphia, Philadelphia, PA, USA; 2Department of Anesthesiology and Critical Care Medicine, The Children’s Hospital of Philadelphia, Philadelphia, PA, USA The Wistar–Kyoto (WKY) rat is stress sensitive and exhibits depressive-like behavior. The locus coeruleus (LC)–norepinephrine and dorsal raphe (DR)–serotonin systems mediate certain aspects of the stress response and have been implicated in depression. Microarray technology was used to identify gene expression differences in the LC and DR between WKY vs Sprague–Dawley (SD) rats that might account for the WKY phenotype. RNA was isolated from microdissected LC and DR, amplified, and hybridized to microarrays (1 array/ subject, n ¼ 4/group). Significance of microarray (SAM) analysis revealed increased expression of 66 genes in the LC and 19 genes in the DR and decreased expression of 33 genes in the DR of WKY rats. Hierarchical clustering identified differences in gene expression profiles of WKY vs SD rats that generally concurred with SAM. Notably, genes that encoded for enzymes involved in norepinephrine turnover, amino-acid receptors, and certain G-protein-coupled receptors were elevated in the LC of WKY rats. The DR of WKY rats showed decreased expression of genes encoding several potassium channels and neurofilament genes. The chromosomal locations of 15 genes that were differentially expressed in WKY rats were near loci identified as contributing to depressive-like behaviors in the rat.
    [Show full text]
  • Regulation of the Glutamate/Glutamine Cycle by Nitric Oxide in the Central Nervous System
    University of Pennsylvania ScholarlyCommons Publicly Accessible Penn Dissertations 2015 Regulation of the Glutamate/glutamine Cycle by Nitric Oxide in the Central Nervous System Karthik Anderson Raju University of Pennsylvania, [email protected] Follow this and additional works at: https://repository.upenn.edu/edissertations Part of the Biochemistry Commons, Biology Commons, and the Neuroscience and Neurobiology Commons Recommended Citation Raju, Karthik Anderson, "Regulation of the Glutamate/glutamine Cycle by Nitric Oxide in the Central Nervous System" (2015). Publicly Accessible Penn Dissertations. 1962. https://repository.upenn.edu/edissertations/1962 This paper is posted at ScholarlyCommons. https://repository.upenn.edu/edissertations/1962 For more information, please contact [email protected]. Regulation of the Glutamate/glutamine Cycle by Nitric Oxide in the Central Nervous System Abstract Nitric oxide (˙NO) is a critical contributor to glutamatergic neurotransmission in the central nervous system (CNS). Much of its influence is due ot the ability of this molecule to regulate protein structure and function through its posttranslational modification of cysteine esidues,r a process known as S- nitrosylation. However, little is known about the extent of this modification and its associated functional effects in the brain under physiological conditions. We employed mass spectrometry (MS)-based methodologies to interrogate the S-nitrosocysteine proteome in wild-type (WT), neuronal nitric oxide synthase-deficient (nNOS-/-),
    [Show full text]
  • Purification and Characterization of Glutamate Decarboxylase
    Food Sci. Technol. Res., 9 (3), 283–287, 2003 Purification and Characterization of Glutamate Decarboxylase from Aspergillus oryzae Kimi TSUCHIYA,1 Kenryo NISHIMURA1 and Masayoshi IWAHARA2 1Kumamoto Industrial Research Institute, Higashimachi, Kumamoto, 862-0901, Japan 2Sojo University, 4-22-1, Ikeda, Kumamoto-City, Kumamoto, 860-0082, Japan Received December 25, 2002; Accepted June 14, 2003 We purified glutamate decarboxylase (GAD) [EC4.1.1.15] from Aspergillus oryzae and characterized its biochem- ical and kinetic properties. GAD was purified by ammonium sulfate at 30–70% saturation and chromatographies on Sephacryl S-300, DEAE-FF and CM-FF. The purification of GAD from the crude enzyme solution was 40-fold and the recovery rate was 4.9%. About 230 ␮g of purified enzyme was obtained from 20 g of the mycelia of A. oryzae. The purified preparation of the enzyme showed a single protein band on SDS-PAGE. The molecular weight of purified GAD by SDS-PAGE and gel filtration was estimated to be 48 kDa and 300 kDa, respectively, suggesting that purified GAD had a hexameric structure. The Km value for L-glutamic acid, a substrate of the enzyme, was estimated to be 13 mM. The optimum pH and temperature of GAD were 5.5 and 60˚C, respectively. The GAD activity was stable up to 40˚C. Keywords: glutamate decarboxylase, Aspergillus oryzae, purification, ␥-amino-butyric acid Glutamate decarboxylase (GAD; EC4.1.1.15) produces ␥- production in food processing by effective utilization of the GAD amino-butyric acid (GABA) from glutamate. GABA has several from A. oryzae. In this study, we purified GAD from the myceli- physiological effects on the human body, including neurotrans- um of A.
    [Show full text]
  • Dependent Enzymes. a Hypothesis Philipp Christen*, Patrik Kasper, Heinz Gehring, Michael Sterk Bioehemisches Institut, Universitgit Ziirich, Winterthurerstr
    FEBS Letters 389 (1996) 12-14 FEBS 16909 Minireview Stereochemical constraint in the evolution of pyridoxal-5'-phosphate- dependent enzymes. A hypothesis Philipp Christen*, Patrik Kasper, Heinz Gehring, Michael Sterk Bioehemisches Institut, Universitgit Ziirich, Winterthurerstr. 190, CH-8057 Ziirieh, Switzerland Received 11 January 1996 cular evolution of B6 enzymes. Alanine aminotransferase, as- Abstract In the transamination reactions undergone by pyri- doxal-5'-phosphate-dependent enzymes that act on L-amino partate aminotransferase, 2,2-dialkylglycine decarboxylase, acids, the C4' atom of the cofactor is without exception glutamate decarboxylase, and serine hydroxymethyltransfer- protonated from the si side. This invariant absolute stereo- ase indeed belong to the large c~ family of homologous B6 chemistry of enzymes not all of which are evolutionarily related enzymes [1-3]. However, the pyridoxal-5'-phosphate-depen- to each other and the inverse stereochemistry in the case of D- dent 13 subunit of tryptophan synthase which shows the alanine aminotransferase might reflect a stereochemical con- same stereochemistry is a member of the [3 family of B6 en- straint in the evolution of these enzymes rather than an zymes which is not homologous with the e~ family [1,4]. accidental historical trait passed on from a common ancestor (About the seventh enzyme, pyridoxamine pyruvate amino- enzyme. Conceivably, the coenzyme and substrate binding sites transferase, no information on primary or tertiary structure of primordial pyridoxal-5'-phosphate-dependent
    [Show full text]
  • The 58-Kilodalton Calmodulin-Binding Glutamate Decarboxylase Is a Ubiquitous Protein in Petunia Organs and Its Expression Is Developmentally Regulated'
    Plant Physiol. (1994) 106: 1381-1387 The 58-Kilodalton Calmodulin-Binding Glutamate Decarboxylase Is a Ubiquitous Protein in Petunia Organs and Its Expression Is Developmentally Regulated' Yali Chen, Gideon Baum, and Hillel Fro"* Department of Plant Genetics, Weizmann Institute of Science, 761O0 Rehovot, Israel et al., 1984); heat shock (Mayer et al., 1990); and water stress A cDNA coding for a 58-kD calcium-dependent calmodulin (Rhodes et al., 1986), which is consistent with this role. (CaM)-binding glutamate decarboxylase (GAD) previously isolated Moreover, GAD activity is enhanced at relatively acidic pH in our laboratory from petunia (Petunia hybrida) (G. Baum, Y. (Snedden et al., 1992; Crawford et al., 1994). It was also Chen, T. Arazi, H. Takatsuji, H. Fromm [1993] J Biol Chem 268: suggested that transamination of a-ketoglutarate by GABA 19610-19617) was used to conduct molecular studies of GAD (producing succinic semialdehyde and glutamate) could reg- expression. GAD expression was studied during petunia organ ulate carbon flow through the tricarboxylic acid cycle by development using the GAD cDNA as a probe to detect the GAD mRNA and by the anti-recombinant GAD serum to monitor the bypassing the direct conversion of a-ketoglutarate to succi- levels of GAD. GAD activity was studied in extracts of organs in nate, a step that may be inhibited under certain physiological the course of development. lhe 58-kD CaM-binding GAD is ex- situations (Dixon and Fowden, 1961). In addition, GABA can pressed in all petunia organs tested (flowers and all floral parts, be transaminated even more effectively with pyruvate to leaves, stems, roots, and seeds).
    [Show full text]
  • 29 Disorders of Neurotransmission
    29 Disorders of Neurotransmission Jaak Jaeken, Cornelis Jakobs, Peter T. Clayton, Ron A. Wevers 29.1 Inborn Errors of Gamma Amino Butyric Acid Metabolism – 361 29.1.1 Gamma Amino Butyric Acid Transaminase Deficiency – 361 29.1.2 Succinic Semialdehyde Dehydrogenase Deficiency – 362 29.2 Inborn Defects of Receptors and Transporters of Neurotransmitters – 362 29.2.1 Hyperekplexia – 362 29.2.2 GABA Receptor Mutation – 363 29.2.3 Mitochondrial Glutamate Transporter Defect – 363 29.3 Inborn Errors of Monoamine Metabolism – 365 29.3.1 Tyrosine Hydroxylase Deficiency – 365 29.3.2 Aromatic L-Aminoacid Decarboxylase Deficiency – 365 29.3.3 Dopamine β-Hydroxylase Deficiency – 366 29.3.4 Monoamine Oxidase-A Deficiency – 366 29.3.5 Guanosine Triphosphate Cyclohydrolase-I Deficiency – 367 29.4 Inborn Disorders Involving Pyridoxine and Pyridoxal Phosphate – 369 29.4.1 Pyridoxine-Responsive Epilepsy – 369 29.4.2 Pyridox(am)ine 5’-Phosphate Oxidase Deficiency – 370 References – 371 360 Chapter 29 · Disorders of Neurotransmission Neurotransmitters The neurotransmitter systems can be divided into and serotonin (. Fig. 29.2), and in many other pathways mainly inhibitory aminoacidergic [J-aminobutyric acid including the glycine cleavage system. A major inhibi- (GABA) and glycine], excitatory aminoacidergic (as- tory neurotransmitter, GABA is present in high concen- partate and glutamate), cholinergic (acetylcholine), tration in the central nervous system, predominantly in monoaminergic (mainly adrenaline, noradrenaline, the gray matter. GABA modulates brain activity by dopamine, and serotonin), and purinergic (adenosine binding to sodium-independent, high-affinity, mostly and adenosine mono-, di-, and triphosphate). A rapidly GABAA receptors. growing list of peptides are also considered putative GLYCINE, a non-essential amino acid, is an inter- neurotransmitters.
    [Show full text]
  • Ultrastructural and Photosynthetic Responses of Pod Walls in Alfalfa to Drought Stress
    International Journal of Molecular Sciences Article Ultrastructural and Photosynthetic Responses of Pod Walls in Alfalfa to Drought Stress Hui Wang 1,2, Qingping Zhou 2 and Peisheng Mao 1,* 1 Forage Seed Laboratory, Key Laboratory of Pratacultural Science, Beijing Municipality, China Agricultural University, Beijing 100193, China; [email protected] 2 College of Qinghai-Tibetan Plateau, Southwest Minzu University, Chengdu 610041, China; [email protected] * Correspondence: [email protected]; Tel.: +86-010-6273-3311 Received: 3 June 2020; Accepted: 22 June 2020; Published: 23 June 2020 Abstract: Increasing photosynthetic ability as a whole is essential for acquiring higher crop yields. Nonleaf green organs (NLGOs) make important contributions to photosynthate formation, especially under stress conditions. However, there is little information on the pod wall in legume forage related to seed development and yield. This experiment is designed for alfalfa (Medicago sativa) under drought stress to explore the photosynthetic responses of pod walls after 5, 10, 15, and 20 days of pollination (DAP5, DAP10, DAP15, and DAP20) based on ultrastructural, physiological and proteomic analyses. Stomata were evidently observed on the outer epidermis of the pod wall. Chloroplasts had intact structures arranged alongside the cell wall, which on DAP5 were already capable of producing photosynthate. The pod wall at the late stage (DAP20) still had photosynthetic ability under well-watered (WW) treatments, while under water-stress (WS), the structure of the chloroplast membrane was damaged and the grana lamella of thylakoids were blurry. The chlorophyll a and chlorophyll b concentrations both decreased with the development of pod walls, and drought stress impeded the synthesis of photosynthetic pigments.
    [Show full text]
  • Cellular Immunity to a Determinant Common to Glutamate Decarboxylase and Coxsackie Virus in Insulin-Dependent Diabetes
    Cellular immunity to a determinant common to glutamate decarboxylase and coxsackie virus in insulin-dependent diabetes. M A Atkinson, … , D L Kaufman, N K Maclaren J Clin Invest. 1994;94(5):2125-2129. https://doi.org/10.1172/JCI117567. Research Article Find the latest version: https://jci.me/117567/pdf Rapid Publication Cellular Immunity to a Determinant Common to Glutamate Decarboxylase and Coxsackie Virus in Insulin-dependent Diabetes Mark A. Atkinson, * Mark A. Bowman, * Lalita Campbell, * Bethany L. Darrow, * Daniel L. Kaufman, * and Noel K. Maclaren * * Department of Pathology and Laboratory Medicine, College of Medicine, University of Florida, Gainesville, Florida 32610; and t Department of Molecular and Medical Pharmacology, University of California-Los Angeles, Los Angeles, California 90024 Abstract Introduction Insulin-dependent diabetes (IDD) results from the autoim- Insulin-dependent diabetes (IDD),' or type 1 diabetes, results mune destruction of the insulin-producing pancreatic 13 from the autoimmune destruction of the insulin-producing pan- cells. Autoreactive T-lymphocytes are thought to play a piv- creatic 6 cells. A chronic mononuclear cell infiltration of the otal role in the pathogenesis of IDD; however, the target pancreatic islet cells is the pathological hallmark of the disease. antigens of these cells, as well as the inductive events in the The lesion is composed predominantly of T-lymphocytes, cells disease, are unclear. PBMC in persons with or at increased which are thought to play a pivotal role in the pathogenesis of risk for IDD show elevated reactivity to the .3 cell enzyme the disorder (1, 2). Islet- or islet-cell protein-reactive PBMC glutamate decarboxylase (GAD).
    [Show full text]
  • Sequences of Canine Glutamate Decarboxylase (GAD) 1 and GAD2 Genes, and Variation of Their Genetic Polymorphisms Among Five Dog Breeds
    NOTE Ethology Sequences of Canine Glutamate Decarboxylase (GAD) 1 and GAD2 Genes, and Variation of their Genetic Polymorphisms among Five Dog Breeds Sayaka ARATA1), Chie HASHIZUME1), Takefumi KIKUSUI1), Yukari TAKEUCHI1)* and Yuji MORI1) 1)Laboratory of Veterinary Ethology, The University of Tokyo, Tokyo 113–8657, Japan (Received 3 March 2008/Accepted 20 May 2008) ABSTRACT. Glutamate decarboxylase (GAD) is the primary enzyme in the brain that catalyzes the synthesis of γ-aminobutyric acid (GABA), the main inhibitory neurotransmitter. There are two isoforms named according to their molecular weights, GAD67 and GAD65, which are encoded by GAD1 and GAD2, respectively. To investigate the association between GAD genes and temperament in domestic dogs, Canis familiaris, we sequenced the full lengths of the coding regions of these genes and identified three single nucleotide polymorphisms (SNPs) in GAD1 and one in GAD2. When comparing genotype and allele frequencies of SNPs among five breeds with different behavioral traits, statistically significant interbreed differences were observed for three SNPs in GAD1. These results suggest that GAD1 SNPs may be useful for behavioral genetic studies in dogs. KEY WORDS: canine, GAD, SNP. J. Vet. Med. Sci. 70(10): 1107–1110, 2008 Gamma-aminobutyric acid (GABA) is the major inhibi- dogs with particular physical traits, behavioral characteris- tory neurotransmitter in the central nervous system. Its tics, or unique skills has resulted in today’s large variety of function was first noted with regard to its suppressive effect breeds, which now exceeds 400 [18]. These breed-specific against convulsions caused by excessive administration of characteristics are likely to reflect the genetic background, glutamate.
    [Show full text]
  • The Genetic Basis of Panic Disorder
    REVIEW Psychiatry & Psychology DOI: 10.3346/jkms.2011.26.6.701 • J Korean Med Sci 2011; 26: 701-710 The Genetic Basis of Panic Disorder Hae-Ran Na, Eun-Ho Kang, Jae-Hon Lee Panic disorder is one of the chronic and disabling anxiety disorders. There has been and Bum-Hee Yu evidence for either genetic heterogeneity or complex inheritance, with environmental factor interactions and multiple single genes, in panic disorder’s etiology. Linkage studies Department of Psychiatry, Samsung Medical Center, Sungkyunkwan University School of Medicine, have implicated several chromosomal regions, but no research has replicated evidence for Seoul, Korea major genes involved in panic disorder. Researchers have suggested several neurotransmitter systems are related to panic disorder. However, to date no candidate Received: 19 January 2011 gene association studies have established specific loci. Recently, researchers have Accepted: 22 March 2011 emphasized genome-wide association studies. Results of two genome-wide association Address for Correspondence: studies on panic disorder failed to show significant associations. Evidence exists for Bum-Hee Yu, MD differences regarding gender and ethnicity in panic disorder. Increasing evidence suggests Department of Psychiatry, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, genes underlying panic disorder overlap, transcending current diagnostic boundaries. In Gangnam-gu, Seoul 135-710, Korea addition, an anxious temperament and anxiety-related personality traits may represent Tel: +82.2-3410-3583, Fax: +82.2-3410-6957 E-mail: [email protected] intermediate phenotypes that predispose to panic disorder. Future research should focus on broad phenotypes, defined by comorbidity or intermediate phenotypes. Genome-wide association studies in large samples, studies of gene-gene and gene-environment interactions, and pharmacogenetic studies are needed.
    [Show full text]