DOCSLIB.ORG

Lipoxygenase Metabolites of Arachidonic Acid in Neuronal

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Lipoxygenase Metabolites of Arachidonic Acid in Neuronal TiPS - September 1990 [Vol. 11] 367 28 Takeda, N. et aL (1986) Acta Otolaryngol. Venerol. (Suppl. 115), 1-43 34 Pipkom, U. et al. (1987) Allergy 101,416-421 32 Granerus, G., Olafsson, I. H. and (Copenhagen) 42, 496-501 29 Tung, A. S. et al. (1985) Biochem. Roupe, G. (1985) Agents Actions 16, Pharmacol. 34, 3509-3515 244-248 30 August, T. F. el al. (1985) J. Pharm. Sci. 33 Neitaanmaki, H., Fraki, ]. E., Harvima, IPDllS1T: dimethyl-2-[4-(3-ethoxy-2- 74, 871-875 R. J. and Forstrom, L. (1989) Arch. hydroxypropoxy)phenylcarbamoyllethyl 31 Olafsson, I. H. (I985) Acta Derm. Dermatol. Res. 281, 99-104 sulfonium-p-toluene sulfonate polyacrylamide gel electrophor- Lipoxygenase metabolites of esis) and has no apparent cofactor requirement 4. A cDNA encoding arachidonic acid in neuronal leukocyte 12-1ipoxygenase has been isolated and sequenced 5. Like all other lipoxygenases, 12- transmembrane signalling lipoxygenase catalyses the intro- duction of molecular oxygen into Daniele Piomelli and Paul Greengard a 1,4-(cis,cis)-pentadiene moiety, converting arachidonic acid into the hydroperoxide, (12s)-hydro- Studies of invertebrate and vertebrate nervous tissue have demonstrated that peroxyeicosatetraenoic acid (12- free arachidonic acid and its lipoxygenase metabolites are produced in a HPETE) - a reaction that is both receptor-dependent fashion. The intracellular actions of these compounds regiospecific and stereospecific. include the regulation of activity of membrane ion channels and protein Other cis-polyunsaturated fatty kinases. In this article Daniele Piomelli and Paul Greengard review the acids, such as linoleic acid, lino- evidence that these lipophilic molecules constitute a novel class of intracellular lenic acid and docosahexaenoic second messenger, possibly involved in the modulation of neurotransmitter acid are also good substrates for release. the leukocyte 12-1ipoxygenase. Many neurotransmitters exert Recent work has suggested that Lipoxygenases in the brain their actions on neurons by stimu- the membrane polyunsaturated In a recent study the levels of lating the formation of intracellu- fatty acid arachidonic acid and its 12-1ipoxygenase in several areas of lar second messengers, which metabolites produced through the porcine brain were estimated by include such diverse molecules as lipoxygenase pathways may con- immunoassay, using a mono- cyclic nucleotides, Ca 2+, inositol stitute a novel class of neuronal clonal antibody raised against 1,4,5-trisphosphate and 1,2-diacyl- second messengers. These lipids, leukocyte 12-1ipoxygenase°. Detect- glycerol. In most cases second which affect the activities of neur- able levels of the enzyme were messengers stimulate the activity onal ion channels and protein found in the cytosolic fractions of specific protein kinases, which kinases, might participate in the of olfactory bulb, hypothalamus, phosphorylate and hence modu- regulation of neurotransmitter cerebellum and pineal body; the late the activity of a large number release. highest |evels were detected in of enzymes, membrane ion chan- Arachidonic acid is found in parenchymal cells of the anterior nels and structural proteins (for esterified form in cell membrane pituitary lobe. review, see Ref. 1). However, phospholipids from which it can Even though 12-HPETE is second messengers can also acti- be liberated through multiple reduced very rapidly to the alco- vate phosphatases either directly enzymatic pathways (see Box 1). It hol (12s)-hydroxyeicosatetraenoic (as in the case of the Ca2+-cal - can then diffuse out of the cell, acid (12-HETE), which has long modulin-dependent phosphatase be reincorporated into phospho- been known to be a major metab- calcineurin), or indirectly through lipids, or undergo metabolism. olite of arachidonic acid in the phosphorylation of phosphatase Three pathways of arachidonic acid brain, the metabolism of 12- inhibitors 2. In some cases, second metabolism have been described HPETE is not limited to its reduc- messengers can act without the in animal tissues: the cyclooxy- tion (Fig. 1). The fatty acid hydro- participation of enzyme inter- genase pathway, the lipoxygenase peroxide can give rise to a group mediates, by binding to mem- pathway and the cytochrome P-450 of biologically active hydroxy- brane ion channels (or to regu- or 'epoxygenase' pathway (Box 1). epoxides, the 'hepoxilins', two of latory proteins closely associated In nervous tissue the major enzy- which - hepoxilin As and hepox- with them) and changing their matic route involved in the metab- ilin I]3 - have been identified in properties (for instance in the case olism of arachidonic acid is the 12- nervous tissue from both ver- of Ca2+-activated K + channels; for lipoxygenase pathway (Box 1 and tebrates and invertebrates 7,s (Fig. review, see Ref. 3). Fig. 1). There is also good evidence 1). The hepoxilins are short-lived for the occurrence in nervous tissue compounds and undergo further of the 5-1ipoxygenase pathway. metabolism by the action of a 12-Lipoxygenase, first isolated hepoxilin hydrolase, which has D. P;omelli is a Postdoctoral Associate and from blood platelets and now been purified from rat liver and P. Gree:rga:'d is Profi'ssor and ttead at tfle shown to be present in brain. This Laboratory o[ Molecular and Celhdar Neuro- purified to near homogeneity science, The Rockefeller University, New from leukocytes, is a cytosolic pro- enzyme catalyses the specific York, NY 10021, USA. tein of 72 kDa (based on SDS- cleavage of the hepoxilin epoxide ~) 1990, Elsevier Science Publishers Lid. (UK) 0165 - b147/901.$02.0i) 368 TiPS - September 1990 [Vol. 11] - Box 1 Pathways of arachidonic Liberation of arachidonic acid from membrane phospho- 1). The two steps required for reincorporation - the lipids mainly occurs by two pathways (Fig. 1). Hydrolytic reactions of arachidonoyl-CoA synthetase and cleavage at the sn-2 position of the glycerophospholipid arachidonoyl-lysophospholipid transferase - are thought backbone, catalysed by Ca2+-activated phospholipase A2, to make up the major mechanism responsible for keeping yields free fatty acid and lysophospholipidL Alternatively, the concentration of free arachidonic acid low within cells. formation of free arachidonic acid can be initiated by the activation of a phospholipase C, which cleaves the phos- The three pathways of arachidonic acid metabolism pholipid at the phosphate ester bond, producing 1,2- described for other animal tissues - cycloo×ygenase, diacylgJycerol. This intermediate is broken down by iipoxygenase and cytochrome P-450 (Ref. 4) - bdve also diacylglycerol-and monoacylglycerol lipases to yield free been found in the brain (for review, see ReL 5). The fatty acid and glycerol-'. cyclooxygenase pathway leads to the formation of prosta- After liberation, free arachidonic acid has several fates. It glandins, prostacyclin (PGI2) and thromboxane A2 (TXA2). can diffuse out of the cell. Alternatively, it can be either Cyclooxygenase is inhibited by some non-steroidal anti- metabolized (see below) or converted to arachidonoyl- inflammatory drugs, such as indometacin, by the anti- coenzyme A and reincorporated into phospholipidss (Fig. oxidant nordihydroguaiaretic acid and by the false sub- strate eicosatetraynoic acid4. ~phospholipid~ Lipoxygenases, which are inhibited nonspecifically by nordihydroguaiaretic acid, eicosatetraynoic acid and baicalein, form hydroperoxyeicosatetraenoic acids polar~ I "X (HPETE) as their primary products. HPETE can undergo a complex metabolism (see main text for details). 5-HPETE, formed by 5-1ipoxygenase, is converted to the short-lived [k, lyso- )~ epoxide leukotriene, LTA4, by a dehydrase activity intrin- •,l, I '~ phospholipid (J I sic to 5-1ipoxygenase6. LTA4 can be transformed either into OA.G AA-CoA LTB4, by an LTA4-hydrolase7, or into LTC4 by a glutathione-S-transferase (GSH-S-transferase)8. 5-Lipoxy- genase activity is specifically inhibited by 5,6-methano- leukotriene A4. methyl ester and 5,6-dehydroarachidonic acid. In addition, fo,-mation of 5-1ipoxygenase products can / \ / be inhibited in intact cells by MK886, which prevents I CoA-S" 5-1ipoxygenase activaUon by binding to a newly described MAG ('~ ~ AA 5-1ipoxygenase activatiz:g protein (FLAP)9. Metabolism of 15-HPETE show.~ considerable similarities to that of 12-HPETE (see Refs 10 and 11). Cytochrome P-450 catalyses the conversion of arachi- donic acid into an array of epoxyeicosatrienoic acids (EET), extracellular metabolism which are hydrolysed to the corresponding diols by the diffusion action of an epoxide hydrolase (inhibited by trichloro- F-~j. I. Pathways of arach~onic acid turnover. AA, arachidonic propene oxide). In addition, cytochrome P-450 has also ac/d; PLA=, phoso,hoiipase A2; PLC, phospholipase C; DAG, been shown to produce hydroxyeicosatetraenoic acids 1,2-diacylglycerol; MAG, monoacylglyceroL (HETE) .2. ring, yielding a family of isomeric arachidonic acid to oxygenated 12-1ipoxygenase, requires both trihydroxy acids termed "trioxi- derivatives (mainly epoxylated Ca 2+ and ATP for maximal ac- lins '9. In addition to hepoxilins and hydroxylated eicosatetraenoic tivity. Upon binding of Ca 2+ the and trioxilins, the nervous tissue acids), some of which are formed enzyme translocates to the cell of the marine mollusk Aplysia cali- in nervous tissue ~2. In addition to membrane, where its lipophilic fornica converts 12-HPETE into this direct role in arachidonic acid substrate, arachidonic acid, is the keto acid, 12-ketoeicosa- metabolism (for review, see Ref. more
Load more

Recommended publications
  • Open Thesis Master Document V5.0.Pdf
    The Pennsylvania State University The Graduate School Department of Veterinary and Biomedical Science IDENTIFICATION OF ENDOGENOUS MODULATORS FOR THE ARYL HYDROCARBON RECEPTOR A Thesis in Genetics by Christopher R. Chiaro © 2007 Christopher R. Chiaro Submitted in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy December, 2007 The thesis of Christopher R. Chiaro was reviewed and approved* by the following: Gary H. Perdew John T. and Paige S. Smith Professor in Agricultural Sciences Thesis Advisor Chair of Committee C. Channa Reddy Distinguished Professor of Veterinary Science A. Daniel Jones Senior Scientist Department of Chemistry John P. Vanden Heuvel Professor of Veterinary Science Richard Ordway Associate Professor of Biology Chair of Genetics Graduate Program *Signatures are on file in the Graduate School iii ABSTRACT The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor capable of being regulated by a structurally diverse array of chemicals ranging from environmental carcinogens to dietary metabolites. A member of the basic helix-loop- helix/ Per-Arnt-Sim (bHLH-PAS) super-family of DNA binding regulatory proteins, the AhR is an important developmental regulator that can be detected in nearly all mammalian tissues. Prior to ligand activation, the AhR resides in the cytosol as part of an inactive oligomeric protein complex comprised of the AhR ligand-binding subunit, a dimer of the 90 kDa heat shock protein, and a single molecule each of the immunophilin like X-associated protein 2 (XAP2) and p23 proteins. Functioning as chemosensor, the AhR responds to both endobiotic and xenobiotic derived chemical ligands by ultimately directing the expression of metabolically important target genes.
    [Show full text]
  • Regulation of Tissue Inflammation by 12-Lipoxygenases
    biomolecules Review Regulation of Tissue Inflammation by 12-Lipoxygenases Abhishek Kulkarni 1 , Jerry L. Nadler 2, Raghavendra G. Mirmira 1,* and Isabel Casimiro 1,* 1 Department of Medicine, The University of Chicago, Chicago, IL 60637, USA; [email protected] 2 Department of Medicine and Pharmacology, New York Medical College, Valhalla, NY 10595, USA; [email protected] * Correspondence: [email protected] (R.G.M.); [email protected] (I.C.) Abstract: Lipoxygenases (LOXs) are lipid metabolizing enzymes that catalyze the di-oxygenation of polyunsaturated fatty acids to generate active eicosanoid products. 12-lipoxygenases (12-LOXs) primarily oxygenate the 12th carbon of its substrates. Many studies have demonstrated that 12-LOXs and their eicosanoid metabolite 12-hydroxyeicosatetraenoate (12-HETE), have significant pathological implications in inflammatory diseases. Increased level of 12-LOX activity promotes stress (both oxidative and endoplasmic reticulum)-mediated inflammation, leading to damage in these tissues. 12-LOXs are also associated with enhanced cellular migration of immune cells—a characteristic of several metabolic and autoimmune disorders. Genetic depletion or pharmacological inhibition of the enzyme in animal models of various diseases has shown to be protective against disease development and/or progression in animal models in the setting of diabetes, pulmonary, cardiovascular, and metabolic disease, suggesting a translational potential of targeting the enzyme for the treatment of several disorders. In this article, we review the role of 12-LOXs in the pathogenesis of several diseases in which chronic inflammation plays an underlying role. Citation: Kulkarni, A.; Nadler, J.L.; Keywords: 12-lipoxygenases; 12-LOXs; 12/15-lipoxygenase; 12/15-LOX; lipoxygenases; eicosanoids; Mirmira, R.G.; Casimiro, I.
    [Show full text]
  • Fatty Acid Metabolism Mediated by 12/15-Lipoxygenase Is a Novel Regulator of Hematopoietic Stem Cell Function and Myelopoiesis
    University of Pennsylvania ScholarlyCommons Publicly Accessible Penn Dissertations Spring 2010 Fatty Acid Metabolism Mediated by 12/15-Lipoxygenase is a Novel Regulator of Hematopoietic Stem Cell Function and Myelopoiesis Michelle Kinder University of Pennsylvania, [email protected] Follow this and additional works at: https://repository.upenn.edu/edissertations Part of the Immunology and Infectious Disease Commons Recommended Citation Kinder, Michelle, "Fatty Acid Metabolism Mediated by 12/15-Lipoxygenase is a Novel Regulator of Hematopoietic Stem Cell Function and Myelopoiesis" (2010). Publicly Accessible Penn Dissertations. 88. https://repository.upenn.edu/edissertations/88 This paper is posted at ScholarlyCommons. https://repository.upenn.edu/edissertations/88 For more information, please contact [email protected]. Fatty Acid Metabolism Mediated by 12/15-Lipoxygenase is a Novel Regulator of Hematopoietic Stem Cell Function and Myelopoiesis Abstract Fatty acid metabolism governs critical cellular processes in multiple cell types. The goal of my dissertation was to investigate the intersection between fatty acid metabolism and hematopoiesis. Although fatty acid metabolism has been extensively studied in mature hematopoietic subsets during inflammation, in developing hematopoietic cells the role of fatty acid metabolism, in particular by 12/ 15-Lipoxygenase (12/15-LOX), was unknown. The observation that 12/15-LOX-deficient (Alox15) mice developed a myeloid leukemia instigated my studies since leukemias are often a consequence of dysregulated hematopoiesis. This observation lead to the central hypothesis of this dissertation which is that polyunsaturated fatty acid metabolism mediated by 12/15-LOX participates in hematopoietic development. Using genetic mouse models and in vitro and in vivo cell development assays, I found that 12/15-LOX indeed regulates multiple stages of hematopoiesis including the function of hematopoietic stem cells (HSC) and the differentiation of B cells, T cells, basophils, granulocytes and monocytes.
    [Show full text]
  • Lipoxygenase-Generated Icosanoids Inhibit Glucose-Induced Insulin Release from Rat Islets
    RostagiamJins Leukotrienes and Essential Fatty Acids (1990) 40.214 @ Longman Group UK Ltd 1990 Lipoxygenase-Generated Icosanoids Inhibit Glucose-induced Insulin Release from Rat Islets M. H. Nathan* and S. Belbez Pekt *Department of Internal Medicine (Division of Endocrinology and Metabolism), University of Michigan, Ann Arbor, Michigan, USA and ‘5560 Medical Sciences Research Building-2, University of Michigan Medical Center, Ann Arbor, MI 48109-0678, USA (Correspondence to SBP) ABSTRACT. Lipoxygenase-pathway metabolites of arachidonic acid are produced in pancreatic islets. They are are implicated in insulin release, since nonselective inhibitors of lipoxygenases inhibit glucose-induced insulin release. We studied the interplay in insulin release between glucose and selected icosanoids formed in 5-, 12- and 15-lipoxygenase pathways. Effects on immunoreactive insulin release of 10’ to 1O-6 12-(R)-HETE, 12-(S)-HETE, hepoxilin As, lipoxin Bq, LTB4 or LTC4 were tested individually in 30-min incubations of freshly isolated young adult Wistar rat pancreatic islets, in the presence of 5.6 mM or 23 mM glucose. Basal insulin release (at 5.6 mM glucose) was stimulated by LTC4 and hepoxilin A3 (304% and 234% of controls at 5.6 mM glucose alone, respectively), inhibited by 12-(S)-HPETE (56%), and was not affected by 12-(R)-HETE, 12-(S)-HETE, lipoxin B4 or LTB4 (ill%, 105%, 106% and 136%, respectively). Insulin release evoked by 23 mM glucose (190-320%) was inhibited (50-145%) by all icosanoids tested, except LTC4 (162%). We conclude that, among the lipoxygenase products tested, only leukotrienes and hepoxilin are candidates for a tonic-stimulatory influence on basal insulin release.
    [Show full text]
  • Metabolism Pathways of Arachidonic Acids: Mechanisms and Potential Therapeutic Targets
    Signal Transduction and Targeted Therapy www.nature.com/sigtrans REVIEW ARTICLE OPEN Metabolism pathways of arachidonic acids: mechanisms and potential therapeutic targets Bei Wang1,2,3, Lujin Wu1,2, Jing Chen1,2, Lingli Dong3, Chen Chen 1,2, Zheng Wen1,2, Jiong Hu4, Ingrid Fleming4 and Dao Wen Wang1,2 The arachidonic acid (AA) pathway plays a key role in cardiovascular biology, carcinogenesis, and many inflammatory diseases, such as asthma, arthritis, etc. Esterified AA on the inner surface of the cell membrane is hydrolyzed to its free form by phospholipase A2 (PLA2), which is in turn further metabolized by cyclooxygenases (COXs) and lipoxygenases (LOXs) and cytochrome P450 (CYP) enzymes to a spectrum of bioactive mediators that includes prostanoids, leukotrienes (LTs), epoxyeicosatrienoic acids (EETs), dihydroxyeicosatetraenoic acid (diHETEs), eicosatetraenoic acids (ETEs), and lipoxins (LXs). Many of the latter mediators are considered to be novel preventive and therapeutic targets for cardiovascular diseases (CVD), cancers, and inflammatory diseases. This review sets out to summarize the physiological and pathophysiological importance of the AA metabolizing pathways and outline the molecular mechanisms underlying the actions of AA related to its three main metabolic pathways in CVD and cancer progression will provide valuable insight for developing new therapeutic drugs for CVD and anti-cancer agents such as inhibitors of EETs or 2J2. Thus, we herein present a synopsis of AA metabolism in human health, cardiovascular and cancer biology, and the signaling pathways involved in these processes. To explore the role of the AA metabolism and potential therapies, we also introduce the current newly clinical studies targeting AA metabolisms in the different disease conditions.
    [Show full text]
  • Anti-ALOX15 Monoclonal Antibody, Clone 4H9 (DCABH-1151) This Product Is for Research Use Only and Is Not Intended for Diagnostic Use
    Anti-ALOX15 monoclonal antibody, clone 4H9 (DCABH-1151) This product is for research use only and is not intended for diagnostic use. PRODUCT INFORMATION Product Overview Mouse monoclonal to 15 Lipoxygenase 1 Antigen Description Converts arachidonic acid to 15S-hydroperoxyeicosatetraenoic acid. Also acts on C-12 of arachidonate as well as on linoleic acid. Immunogen Recombinant full length, Human 15 Lipoxygenase 1 produced in HEK293T cells (NP_001131). Isotype IgG2b Source/Host Mouse Species Reactivity Rat, Dog, Human, Monkey Clone 4H9 Purity Protein A purified Purification Purified from Mouse ascites fluids by affinity chromatography Conjugate Unconjugated Applications WB, IHC-P, ICC/IF Positive Control HEK293T cells transfected with pCMV6-ENTRY 15 Lipoxygenase 1 cDNA; HepG2, HeLa, A549, COS7, MDCK, PC12 and MCF7 cell extracts; Human breast, Human pancreas carcinoma, Human thyroid carcinoma, Human endometrium, Human endometrium adenocarcinoma, Human pros Format Liquid Size 100 μl Buffer pH: 7.30; Preservative: 0.02% Sodium azide; Constituents: 48% PBS, 50% Glycerol, 1% BSA Preservative 0.02% Sodium Azide Storage store at -20°C. Avoid repeated freeze / thaw cycles. Ship Shipped at 4°C. 45-1 Ramsey Road, Shirley, NY 11967, USA Email: [email protected] Tel: 1-631-624-4882 Fax: 1-631-938-8221 1 © Creative Diagnostics All Rights Reserved GENE INFORMATION Gene Name ALOX15 arachidonate 15-lipoxygenase [ Homo sapiens ] Official Symbol ALOX15 Synonyms ALOX15; arachidonate 15-lipoxygenase; 15 LOX 1; 15-LOX; 15-lipooxygenase-1; arachidonate
    [Show full text]
  • 3 Requires the Eicosanoid Hepoxilin a Pseudomonas Aeruginosa
    Polymorphonuclear Cell Transmigration Induced by Pseudomonas aeruginosa Requires the Eicosanoid Hepoxilin A 3 This information is current as Bryan P. Hurley, Dario Siccardi, Randall J. Mrsny and Beth of September 24, 2021. A. McCormick J Immunol 2004; 173:5712-5720; ; doi: 10.4049/jimmunol.173.9.5712 http://www.jimmunol.org/content/173/9/5712 Downloaded from References This article cites 40 articles, 19 of which you can access for free at: http://www.jimmunol.org/content/173/9/5712.full#ref-list-1 http://www.jimmunol.org/ Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication by guest on September 24, 2021 *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2004 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology Polymorphonuclear Cell Transmigration Induced by 1 Pseudomonas aeruginosa Requires the Eicosanoid Hepoxilin A3 Bryan P. Hurley,*† Dario Siccardi,*†‡ Randall J. Mrsny,† and Beth A. McCormick2*† Lung inflammation resulting from bacterial infection of the respiratory mucosal surface in diseases such as cystic fibrosis and pneumonia contributes significantly to the pathology.
    [Show full text]
  • Oxidation of Polyunsaturated Fatty Acids to Produce Lipid Mediators
    Essays in Biochemistry (2020) 64 401–421 https://doi.org/10.1042/EBC20190082 Review Article Oxidation of polyunsaturated fatty acids to produce lipid mediators William W. Christie1 and John L. Harwood2 1James Hutton Institute, Invergowrie, Dundee, Scotland DD2 5DA, U.K.; 2School of Biosciences, Cardiff University, Cardiff CF10 3AX, Wales, U.K. Correspondence: John L. Harwood ([email protected]) Downloaded from http://portlandpress.com/essaysbiochem/article-pdf/64/3/401/893636/ebc-2019-0082c.pdf by guest on 29 September 2021 The chemistry, biochemistry, pharmacology and molecular biology of oxylipins (defined as a family of oxygenated natural products that are formed from unsaturated fatty acids by pathways involving at least one step of dioxygen-dependent oxidation) are complex and occasionally contradictory subjects that continue to develop at an extraordinarily rapid rate. The term includes docosanoids (e.g. protectins, resolvins and maresins, or special- ized pro-resolving mediators), eicosanoids and octadecanoids and plant oxylipins, which are derived from either the omega-6 (n-6) or the omega-3 (n-3) families of polyunsaturated fatty acids. For example, the term eicosanoid is used to embrace those biologically active lipid mediators that are derived from C20 fatty acids, and include prostaglandins, thrombox- anes, leukotrienes, hydroxyeicosatetraenoic acids and related oxygenated derivatives. The key enzymes for the production of prostanoids are prostaglandin endoperoxide H synthases (cyclo-oxygenases), while lipoxygenases and oxidases of the cytochrome P450 family pro- duce numerous other metabolites. In plants, the lipoxygenase pathway from C18 polyunsat- urated fatty acids yields a variety of important products, especially the jasmonates, which have some comparable structural features and functions.
    [Show full text]
  • Emerging Perspectives on Pain Management by Modulation of TRP Channels and ANO1
    International Journal of Molecular Sciences Review Emerging Perspectives on Pain Management by Modulation of TRP Channels and ANO1 1, , 2, , 3, , 2, , Yasunori Takayama * y, Sandra Derouiche * y, Kenta Maruyama * y and Makoto Tominaga * y 1 Department of Physiology, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa, Tokyo 142-8555, Japan 2 Thermal Biology group, Exploratory Research Center on Life and Living Systems, National Institutes for Natural Sciences, 5-1 Aza-higashiyama, Myodaiji, Okazaki, Aichi 444-8787, Japan 3 National Institute for Physiological Sciences, National Institutes for Natural Sciences, 5-1 Aza-higashiyama, Myodaiji, Okazaki, Aichi 444-8787, Japan * Correspondence: [email protected] (Y.T.); [email protected] (S.D.); [email protected] (K.M.); [email protected] (M.T.) These authors contributed equally. y Received: 28 May 2019; Accepted: 9 July 2019; Published: 11 July 2019 Abstract: Receptor-type ion channels are critical for detection of noxious stimuli in primary sensory neurons. Transient receptor potential (TRP) channels mediate pain sensations and promote a variety of neuronal signals that elicit secondary neural functions (such as calcitonin gene-related peptide [CGRP] secretion), which are important for physiological functions throughout the body. In this review, we focus on the involvement of TRP channels in sensing acute pain, inflammatory pain, headache, migraine, pain due to fungal infections, and osteo-inflammation. Furthermore, action potentials mediated via interactions between TRP channels and the chloride channel, anoctamin 1 (ANO1), can also generate strong pain sensations in primary sensory neurons. Thus, we also discuss mechanisms that enhance neuronal excitation and are dependent on ANO1, and consider modulation of pain sensation from the perspective of both cation and anion dynamics.
    [Show full text]
  • Hepoxilin B3 and Its Enzymatically Formed Derivative Trioxilin B3 Are Incorporated Into Phospholipids in Psoriatic Lesions
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector Hepoxilin B3 and its Enzymatically Formed Derivative Trioxilin B3 are Incorporated into Phospholipids in Psoriatic Lesions Rosa AntoÂn, Mercedes Camacho, LuõÂs Puig, and LuõÂs Vila Laboratory of In¯ammation Mediators, Institute of Research of the Santa Creu i Sant Pau Hospital, Barcelona, Spain In previous studies we observed that normal human position of glycerophospholipids. The thin layer epidermis forms 12-oxo-eicosatetraenoic acid (12- chromatography analysis of the phospholipid classes 14 oxo-ETE) and hepoxilin B3 (HxB3) as major eicosa- after incubation of epidermal cells with [ C]-labeled noids, both being elevated in psoriasis. We also HxB3, TrXB3, 12-hydroxy-eicosatetraenoic acid (12- observed that normal epidermis, in a reaction prob- HETE), 12-oxo-ETE, or 15-HETE showed that 12- ably catalyzed by 12-lipoxygenase, only synthesize HETE was the most esteri®ed (12-HETE > 15-HETE one of the two possible 10-hydroxy epimers of > TrXB3 > 12-oxo-ETE > HxB3). HxB3 and TrXB3 HxB3. We have now extended these previous studies were mainly esteri®ed in phosphatidyl-choline and investigating further transformation of HxB3 into phosphatidyl-ethanolamine. HxB3 was also enzyma- trioxilin B3 (TrXB3) and esteri®cation of both into tically converted into TrXB3 in vitro. HxB3 epoxide phospholipids. Phospholipids were extracted from hydrolase-like activity was not observed when boiled 14 normal epidermis and from psoriatic scales. A com- tissue was incubated with [ C]-HxB3, this activity bination of high performance liquid chromatography being located in the cytosol fraction (100,000 3 g and gas chromatography±mass spectrometry analysis supernatant) of fresh tissue.
    [Show full text]
  • Schneider, C., Schwab, W., Humpf, H.-U., and Schreier, P
    Curriculum Vitae Name: Dr. Claus Schneider Office Address: 514A RRB Office Phone: 615-343-9539 Email: [email protected] Date and Place of Birth: 27 December 1966 in Karlstadt, Germany Citizenship: German and U.S. Personal data Home Address: 1102 Riverside Rd. Old Hickory, TN 37138, U.S.A. Home Phone: 615-847-2316 Education 09/77 – 05/86 High school Johann-Schöner-Gymnasium, Karlstadt, Germany 03/87 – 10/88 Community service (alternative military service) 10/88 – 12/92 College Universität Würzburg, Germany (Food Chemistry; 1. Staatsexamen) 04/94 – 07/96 Universität Würzburg, Germany (Philosophy, Linguistics, and Political Sciences) 01/93 – 10/96 Graduate School (Dissertation) Department of Food Chemistry, Universität Würzburg, Germany Supervisor: Prof. Dr. Peter Schreier; Title: “Über den Metabolismus von Fettsäurehydroperoxiden in Pflanzen: Untersuchungen zu Substraten und Produkten der Allenoxidsynthase (EC 4.2.1.92) aus Leinsamen (Linum usitatissimum L.)” 05/97 Degree: Ph.D. (Dr. rer. nat.) 01/97 – 07/97 Internship Landesuntersuchungsamt für das Gesundheitswesen Nordbayern, Erlangen, Germany (State food control laboratory) 08/97 Degree: Staatlich geprüfter Lebensmittelchemiker (2. Staatsexamen) 02/98 – 06/01 Postgraduate Training Department of Pharmacology, Vanderbilt University Medical School, Nashville, TN. Mentor: Alan R. Brash, Ph.D. Academic Appointments 10/13 – present Associate Professor Department of Pharmacology, Vanderbilt University Medical School 11/06 – 09/13 Assistant Professor Department of Pharmacology,
    [Show full text]
  • NIH Public Access Author Manuscript Nat Neurosci
    NIH Public Access Author Manuscript Nat Neurosci. Author manuscript; available in PMC 2015 February 01. NIH-PA Author ManuscriptPublished NIH-PA Author Manuscript in final edited NIH-PA Author Manuscript form as: Nat Neurosci. 2014 February ; 17(2): 164–174. doi:10.1038/nn.3612. Peripheral gating of pain signals by endogenous analgesic lipids Daniele Piomelli1,2 and Oscar Sasso2 1Departments of Anatomy and Neurobiology, Pharmacology and Biological Chemistry, University of California, Irvine, USA 92697 2Department of Drug Discovery and Development, Istituto Italiano di Tecnologia, Genoa, Italy 16163 Abstract Primary sensory afferents and their neighboring host-defense cells are a rich source of lipid- derived mediators that contribute to the sensation of pain caused by tissue damage and inflammation. But an increasing number of lipid molecules have been shown to act in an opposite way, to suppress the inflammatory process, restore homeostasis in damaged tissues and attenuate pain sensitivity by regulating neural pathways that transmit nociceptive signals from the periphery of the body to the central nervous system. The ‘gate control theory’ of pain postulates that neural circuits in the central nervous system (CNS) dynamically regulate nociceptive signals arising in the periphery of the body. Since its formulation in 19651, this theory has provided a framework in which to interpret the actions of central analgesic circuits, such as those recruited during acute stress or placebo responses. Emerging evidence indicates, however, that nociceptive signals may be subject to a dynamic filtering process even before they reach the spinal cord. Primary sensory neurons and the host-defense cells surrounding them release a variety of analgesic factors that control the traffic of nociceptive information to the CNS (Figure 1).
    [Show full text]