Ceramide and Related Molecules in Viral Infections
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Mrna Expression of SMPD1 Encoding Acid Sphingomyelinase Decreases Upon Antidepressant Treatment
International Journal of Molecular Sciences Article mRNA Expression of SMPD1 Encoding Acid Sphingomyelinase Decreases upon Antidepressant Treatment Cosima Rhein 1,2,* , Iulia Zoicas 1 , Lena M. Marx 1, Stefanie Zeitler 1, Tobias Hepp 2,3, Claudia von Zimmermann 1, Christiane Mühle 1 , Tanja Richter-Schmidinger 1, Bernd Lenz 1,4 , Yesim Erim 2, Martin Reichel 1,† , Erich Gulbins 5 and Johannes Kornhuber 1 1 Department of Psychiatry and Psychotherapy, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Schwabachanlage 6, D-91054 Erlangen, Germany; [email protected] (I.Z.); [email protected] (L.M.M.); [email protected] (S.Z.); [email protected] (C.v.Z.); [email protected] (C.M.); [email protected] (T.R.-S.); [email protected] (B.L.); [email protected] (M.R.); [email protected] (J.K.) 2 Department of Psychosomatic Medicine and Psychotherapy, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), D-91054 Erlangen, Germany; [email protected] (T.H.); [email protected] (Y.E.) 3 Institute of Medical Informatics, Biometry and Epidemiology, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), D-91054 Erlangen, Germany 4 Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health (CIMH), Medical Faculty Mannheim, Heidelberg University, D-68159 Mannheim, Germany 5 Department of Molecular Biology, University Hospital, University of Duisburg-Essen, D-45147 Essen, Germany; [email protected] * Correspondence: [email protected]; Tel.: +49-9131-85-44542 Citation: Rhein, C.; Zoicas, I.; Marx, † Current address: Department of Nephrology and Medical Intensive Care, Charité—Universitätsmedizin L.M.; Zeitler, S.; Hepp, T.; von Berlin, Berlin, Germany. -
K+ Channel Modulators Product ID Product Name Description D3209 Diclofenac Sodium Salt NSAID; COX-1/2 Inhibitor, Potential K+ Channel Modulator
K+ Channel Modulators Product ID Product Name Description D3209 Diclofenac Sodium Salt NSAID; COX-1/2 inhibitor, potential K+ channel modulator. G4597 18β-Glycyrrhetinic Acid Triterpene glycoside found in Glycyrrhiza; 15-HPGDH inhibitor, hERG and KCNA3/Kv1.3 K+ channel blocker. A4440 Allicin Organosulfur found in garlic, binds DNA; inwardly rectifying K+ channel activator, L-type Ca2+ channel blocker. P6852 Propafenone Hydrochloride β-adrenergic antagonist, Kv1.4 and K2P2 K+ channel blocker. P2817 Phentolamine Hydrochloride ATP-sensitive K+ channel activator, α-adrenergic antagonist. P2818 Phentolamine Methanesulfonate ATP-sensitive K+ channel activator, α-adrenergic antagonist. T7056 Troglitazone Thiazolidinedione; PPARγ agonist, ATP-sensitive K+ channel blocker. G3556 Ginsenoside Rg3 Triterpene saponin found in species of Panax; γ2 GABA-A agonist, Kv7.1 K+ channel activator, α10 nAChR antagonist. P6958 Protopanaxatriol Triterpene sapogenin found in species of Panax; GABA-A/C antagonist, slow-activating delayed rectifier K+ channel blocker. V3355 Vindoline Semi-synthetic vinca alkaloid found in Catharanthus; Kv2.1 K+ channel blocker and H+/K+ ATPase inhibitor. A5037 Amiodarone Hydrochloride Voltage-gated Na+, Ca2+, K+ channel blocker, α/β-adrenergic antagonist, FIASMA. B8262 Bupivacaine Hydrochloride Monohydrate Amino amide; voltage-gated Na+, BK/SK, Kv1, Kv3, TASK-2 K+ channel inhibitor. C0270 Carbamazepine GABA potentiator, voltage-gated Na+ and ATP-sensitive K+ channel blocker. C9711 Cyclovirobuxine D Found in Buxus; hERG K+ channel inhibitor. D5649 Domperidone D2/3 antagonist, hERG K+ channel blocker. G4535 Glimepiride Sulfonylurea; ATP-sensitive K+ channel blocker. G4634 Glipizide Sulfonylurea; ATP-sensitive K+ channel blocker. I5034 Imiquimod Imidazoquinoline nucleoside analog; TLR-7/8 agonist, KCNA1/Kv1.1 and KCNA2/Kv1.2 K+ channel partial agonist, TREK-1/ K2P2 and TRAAK/K2P4 K+ channel blocker. -
Sphingolipid Metabolism Diseases ⁎ Thomas Kolter, Konrad Sandhoff
View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector Biochimica et Biophysica Acta 1758 (2006) 2057–2079 www.elsevier.com/locate/bbamem Review Sphingolipid metabolism diseases ⁎ Thomas Kolter, Konrad Sandhoff Kekulé-Institut für Organische Chemie und Biochemie der Universität, Gerhard-Domagk-Str. 1, D-53121 Bonn, Germany Received 23 December 2005; received in revised form 26 April 2006; accepted 23 May 2006 Available online 14 June 2006 Abstract Human diseases caused by alterations in the metabolism of sphingolipids or glycosphingolipids are mainly disorders of the degradation of these compounds. The sphingolipidoses are a group of monogenic inherited diseases caused by defects in the system of lysosomal sphingolipid degradation, with subsequent accumulation of non-degradable storage material in one or more organs. Most sphingolipidoses are associated with high mortality. Both, the ratio of substrate influx into the lysosomes and the reduced degradative capacity can be addressed by therapeutic approaches. In addition to symptomatic treatments, the current strategies for restoration of the reduced substrate degradation within the lysosome are enzyme replacement therapy (ERT), cell-mediated therapy (CMT) including bone marrow transplantation (BMT) and cell-mediated “cross correction”, gene therapy, and enzyme-enhancement therapy with chemical chaperones. The reduction of substrate influx into the lysosomes can be achieved by substrate reduction therapy. Patients suffering from the attenuated form (type 1) of Gaucher disease and from Fabry disease have been successfully treated with ERT. © 2006 Elsevier B.V. All rights reserved. Keywords: Ceramide; Lysosomal storage disease; Saposin; Sphingolipidose Contents 1. Sphingolipid structure, function and biosynthesis ..........................................2058 1.1. -
The Neutral Glycosphingolipid Globotriaosylceramide Promotes Fusion Mediated by a CD4-Dependent CXCR4-Utilizing HIV Type 1 Envelope Glycoprotein
Proc. Natl. Acad. Sci. USA Vol. 95, pp. 14435–14440, November 1998 Medical Sciences The neutral glycosphingolipid globotriaosylceramide promotes fusion mediated by a CD4-dependent CXCR4-utilizing HIV type 1 envelope glycoprotein ANU PURI*, PETER HUG*, KRISTINE JERNIGAN*, JOSEPH BARCHI†,HEE-YONG KIM‡,JILLON HAMILTON‡, i JOE¨LLE WIELS§,GARY J. MURRAY¶,ROSCOE O. BRADY¶, AND ROBERT BLUMENTHAL* *Section of Membrane Structure and Function, Laboratory of Experimental and Computational Biology, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Frederick, MD 21702; †Laboratory of Medicinal Chemistry, Division of Basic Sciences, National Cancer Institute and ¶Developmental and Metabolic Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892; ‡Laboratory of Membrane Biochemistry and Biophysics, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, MD 20852; and §Centre National de la Recherche Scientifique Unite´Mixte de Recherche 1598, Institut Gustave Roussy, Villejuif Cedex 94805, France Contributed by Roscoe O. Brady, September 25, 1998 ABSTRACT Previously, we showed that the addition of enabling individual HIV strains to choose between alternate human erythrocyte glycosphingolipids (GSLs) to nonhuman modes of entry into cells. CD41 or GSL-depleted human CD41 cells rendered those cells The GSL hypothesis is based on a number of observations, susceptible to HIV-1 envelope glycoprotein-mediated cell fu- including recovery of fusion of nonsusceptible cells after sion. Individual components in the GSL mixture were isolated transfer of protease- and heat-resistant components from by fractionation on a silica-gel column and incorporated into human erythrocytes (12, 13), physicochemical studies on the the membranes of CD41 cells. -
Rediscovery of Fexinidazole
New Drugs against Trypanosomatid Parasites: Rediscovery of Fexinidazole INAUGURALDISSERTATION zur Erlangung der Würde eines Doktors der Philosophie vorgelegt der Philosophisch-Naturwissenschaftlichen Fakultät der Universität Basel von Marcel Kaiser aus Obermumpf, Aargau Basel, 2014 Originaldokument gespeichert auf dem Dokumentenserver der Universität Basel edoc.unibas.ch Dieses Werk ist unter dem Vertrag „Creative Commons Namensnennung-Keine kommerzielle Nutzung-Keine Bearbeitung 3.0 Schweiz“ (CC BY-NC-ND 3.0 CH) lizenziert. Die vollständige Lizenz kann unter creativecommons.org/licenses/by-nc-nd/3.0/ch/ eingesehen werden. 1 Genehmigt von der Philosophisch-Naturwissenschaftlichen Fakultät der Universität Basel auf Antrag von Prof. Reto Brun, Prof. Simon Croft Basel, den 10. Dezember 2013 Prof. Dr. Jörg Schibler, Dekan 2 3 Table of Contents Acknowledgement .............................................................................................. 5 Summary ............................................................................................................ 6 Zusammenfassung .............................................................................................. 8 CHAPTER 1: General introduction ................................................................. 10 CHAPTER 2: Fexinidazole - A New Oral Nitroimidazole Drug Candidate Entering Clinical Development for the Treatment of Sleeping Sickness ........ 26 CHAPTER 3: Anti-trypanosomal activity of Fexinidazole – A New Oral Nitroimidazole Drug Candidate for the Treatment -
Sphingolipids and Cell Signaling: Relationship Between Health and Disease in the Central Nervous System
Preprints (www.preprints.org) | NOT PEER-REVIEWED | Posted: 6 April 2021 doi:10.20944/preprints202104.0161.v1 Review Sphingolipids and cell signaling: Relationship between health and disease in the central nervous system Andrés Felipe Leal1, Diego A. Suarez1,2, Olga Yaneth Echeverri-Peña1, Sonia Luz Albarracín3, Carlos Javier Alméciga-Díaz1*, Angela Johana Espejo-Mojica1* 1 Institute for the Study of Inborn Errors of Metabolism, Faculty of Science, Pontificia Universidad Javeriana, Bogotá D.C., 110231, Colombia; [email protected] (A.F.L.), [email protected] (D.A.S.), [email protected] (O.Y.E.P.) 2 Faculty of Medicine, Universidad Nacional de Colombia, Bogotá D.C., Colombia; [email protected] (D.A.S.) 3 Nutrition and Biochemistry Department, Faculty of Science, Pontificia Universidad Javeriana, Bogotá D.C., Colombia; [email protected] (S.L.A.) * Correspondence: [email protected]; Tel.: +57-1-3208320 (Ext 4140) (C.J.A-D.). [email protected]; Tel.: +57-1-3208320 (Ext 4099) (A.J.E.M.) Abstract Sphingolipids are lipids derived from an 18-carbons unsaturated amino alcohol, the sphingosine. Ceramide, sphingomyelins, sphingosine-1-phosphates, gangliosides and globosides, are part of this group of lipids that participate in important cellular roles such as structural part of plasmatic and organelle membranes maintaining their function and integrity, cell signaling response, cell growth, cell cycle, cell death, inflammation, cell migration and differentiation, autophagy, angiogenesis, immune system. The metabolism of these lipids involves a broad and complex network of reactions that convert one lipid into others through different specialized enzymes. Impairment of sphingolipids metabolism has been associated with several disorders, from several lysosomal storage diseases, known as sphingolipidoses, to polygenic diseases such as diabetes and Parkinson and Alzheimer diseases. -
Occurrence of Sulfatide As a Major Glycosphingolipid in WHHL Rabbit Serum Lipoproteins1
J. Biochem. 102, 83-92 (1987) Occurrence of Sulfatide as a Major Glycosphingolipid in WHHL Rabbit Serum Lipoproteins1 Atsushi HARA and Tamotsu TAKETOMI Department of Lipid Biochemistry, Institute of Cardiovascular Disease , Shinshu University School of Medicine, Matsumoto , Nagano 390 Received for publication, February 12, 1987 Glycosphingolipids in serum and lipoproteins from Watanabe hereditable hyper li pidemic rabbit (WHHL rabbit), which is an animal model for human familial hypercholesterolemia (FH), were analyzed for the first time in this study . Chylo microns and very low density, low density, and high density lipoproteins contained sulfatide as a major glycosphingolipid (12nmol/ƒÊmol total phospholipids (PL) in chylomicrons, 19nmol/ƒÊmol PL in VLDL, 18nmol/ƒÊmol PL in LDL, and 14nmol/ƒÊ mol PL in HDL) with other minor glycosphingolipids such as glucosylceramide, galactosylceramide, GM3 ganglioside, lactosylceramide, and globotriaosylceramide. The concentration of sulfatide as a major glycosphingolipid in WHHL rabbit serum (121nmol/ml) was much higher than that in normal rabbit serum (3nmol/ml). Fatty acids of the sulfatides comprised mainly nonhydroxy fatty acids (C22, 23, and 24) and significant amounts of hydroxy fatty acids (about 10%), whereas long chain bases of the sulfatides comprised mostly (4E)-sphingenine with a significant amount of 4D-hydroxysphinganine (about 10%). Furthermore, sulfatides in the liver and small intestine from normal and WHHL rabbits (where serum lipoproteins are produced) were determined to amount to 260nmol/g liver in WHHL rabbit, 104 nmol/g liver in control rabbit, 99.6nmol/g small intestine in WHHL rabbit, and 31.2nmol/g small intestine in control rabbit. Ceramide portions of the sulfatides in the liver were mainly composed of (4E)-sphingenine and nonhydroxy fatty acids, while those in the small intestine were mainly composed of 4D-hydroxysphinganine and hydroxy fatty acids. -
No Involvement of Acid Sphingomyelinase in the Secretion of IL-6 From
1 No Involvement of Acid Sphingomyelinase in the Secretion of IL-6 from Alveolar Macrophages in Rat Tomoo Ito, Chikako Oyama, Hirokazu Arai, Tsutomu Takahashi Department of Pediatrics, Akita University Graduate School of Medicine, Akita-shi, Akita, 010-8543, Japan Correspondence: Tsutomu Takahashi, M.D. Department of Pediatrics, Akita University Graduate School of Medicine, 1-1-1 hondo, Akita 010-8543, Japan Tel: 018-884-6159 FAX: 018-836-2620 E-mail: [email protected] 1 2 Key words: chronic lung disease of the newborn, alveolar macrophage, acid sphingomyelinase, Running title: Acid Sphingomyelinase in CLD of the Newborn 2 3 Abstract Chronic lung disease (CLD) of the newborn is a major problem in neonatology. Activation of alveolar macrophages has been implicated in the pathogenesis of CLD. Acid sphingomyelinase (ASM) responds to diverse cellular stressors, including lipopolysaccharide (LPS) stimulation. Recently, functional inhibitors of acid sphingomyelinase (FIASMAs) have been described as a large group of compounds that inhibit ASM. Here, we used maternal intra-peritoneal LPS injection to model CLD in the infant rat lung. Using this model, we studied ASM activity in the infant rat lung and the effects of FIASMAs on release of interleukin-6 (IL-6) from LPS-stimulated alveolar macrophages. Maternal exposure to LPS non-significantly increased ASM activities in the infant rat lung. FIASMAs significantly decreased ASM activity of LPS-stimulated alveolar macrophages. In addition, some FIASMAs suppressed the release of IL-6 from LPS-stimulated alveolar macrophages during the early response phase. However, FIASMAs did not suppress the release of IL-6 from LPS-stimulated alveolar macrophages. -
Gb3 and Lyso-Gb3 and Fabry Disease
O H 5 OH OH C17 3 O OH OH O OH NH H C13H27 O O HAc O O N O O O O OH O OH O O OH H H HO O H CO2 H O CO2 AcHN HO HO O O H AcHN O H HO CO2 O H O C 2 O HO H O O H H AcHN O H HO O H cHN O A HO OH N E W S L E T T E R F O R G LY C O / S P H I N G O L I P I D R E S E A R C H D E C E M B E R Gb 2 0 1 9 3 and lyso -Gb 3 and Fabry Disease males. Fabry disease is a multi Fabry disease is caused by deficiency-systemic in the xalpha age of sphingolipids such as lyso -linked disorder with variable prevalence ranging from 1:3000 to 1:117000 in newborn Enzyme replacement therapy (ERT) of the disease has been available since 2001. Several studies support the clinical benefit o towards quality of life, disease progression,-Gb3 and andGb3 stabilization and-galactosidase galabiosyl of endceramide enzyme. organ (Ga2)structure Decrease in organs, and in alphafunction. tissues, and biological fluids. Thurberg 2 evaluated 48 Fabry patients on ERT and found good correlation of urinary Gb3 excretion normalized to creatine. However other studies indicated incomplete relationships between plasma and urinary Gb3 levels and disease-galactosidase manifestations. enzyme Recently, leads to the sto group 3 postulated Gb3 metabolite could play a role in Fabry pathogenesis and reposted the presence of lyso lyso-Gb3 were found in the plasma of Fabry patients and concentrations were reduced after ERT. -
Konzentrationsabhängige Funktionelle Hemmung Der Sauren Sphingomyelinase Durch Antidepressiva
Friedrich-Alexander-Universität Erlangen-Nürnberg Universitätsklinikum Erlangen Psychiatrische und Psychotherapeutische Klinik Direktor: Prof. Dr. Johannes Kornhuber Konzentrationsabhängige funktionelle Hemmung der sauren Sphingomyelinase durch Antidepressiva Inaugural-Dissertation zur Erlangung der Doktorwürde der Medizinischen Fakultät der Friedrich-Alexander-Universität Erlangen-Nürnberg vorgelegt von Sven Städtler aus Kulmbach Gedruckt mit Erlaubnis der Medizinischen Fakultät der Friedrich-Alexander-Universität Erlangen Nürnberg Dekan: Prof. Dr. med. Dr. h.c. Jürgen Schüttler Referent: Prof. Dr. med. Johannes Kornhuber Korreferent: PD Dr. med. Juan Manuel Maler Tag der Mündlichen Prüfung: 30. März 2011 Meinen Eltern gewidmet Inhaltsverzeichnis 1 Zusammenfassung ..................................................................................................... 7 1.1 Hintergrund und Ziele ........................................................................................ 7 1.2 Material und Methode ........................................................................................ 7 1.3 Ergebnisse .......................................................................................................... 8 1.4 Schlussfolgerungen ............................................................................................ 8 2 Abstract ..................................................................................................................... 9 2.1 Background and Aims ....................................................................................... -
VIEW Open Access T-Cell Metabolism in Autoimmune Disease Zhen Yang1, Eric L Matteson2, Jörg J Goronzy1 and Cornelia M Weyand1*
Yang et al. Arthritis Research & Therapy (2015) 17:29 DOI 10.1186/s13075-015-0542-4 REVIEW Open Access T-cell metabolism in autoimmune disease Zhen Yang1, Eric L Matteson2, Jörg J Goronzy1 and Cornelia M Weyand1* Abstract Cancer cells have long been known to fuel their pathogenic growth habits by sustaining a high glycolytic flux, first described almost 90 years ago as the so-called Warburg effect. Immune cells utilize a similar strategy to generate the energy carriers and metabolic intermediates they need to produce biomass and inflammatory mediators. Resting lymphocytes generate energy through oxidative phosphorylation and breakdown of fatty acids, and upon activation rapidly switch to aerobic glycolysis and low tricarboxylic acid flux. T cells in patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) have a disease-specific metabolic signature that may explain, at least in part, why they are dysfunctional. RA T cells are characterized by low adenosine triphosphate and lactate levels and increased availability of the cellular reductant NADPH. This anti-Warburg effect results from insufficient activity of the glycolytic enzyme phosphofructokinase and differentiates the metabolic status in RA T cells from those in cancer cells. Excess production of reactive oxygen species and a defect in lipid metabolism characterizes metabolic conditions in SLE T cells. Owing to increased production of the glycosphingolipids lactosylceramide, globotriaosylceramide and monosialotetrahexosylganglioside, SLE T cells change membrane raft formation and fail to phosphorylate pERK, yet hyperproliferate. Borrowing from cancer metabolomics, the metabolic modifications occurring in autoimmune disease are probably heterogeneous and context dependent. Variations of glucose, amino acid and lipid metabolism in different disease states may provide opportunities to develop biomarkers and exploit metabolic pathways as therapeutic targets. -
The Kidney in Fabry Disease: More Than ª the Author(S) 2016 DOI: 10.1177/2326409816648169 Mere Sphingolipids Overload Iem.Sagepub.Com
Original Article Journal of Inborn Errors of Metabolism & Screening 2016, Volume 4: 1–5 The Kidney in Fabry Disease: More Than ª The Author(s) 2016 DOI: 10.1177/2326409816648169 Mere Sphingolipids Overload iem.sagepub.com Herna´n Trimarchi, MD, PhD1 Abstract Fabry disease is a rare cause of end-stage renal disease. Renal pathology is notable for diffuse deposition of glycosphingolipid in the renal glomeruli, tubules, and vasculature. Classical patients with mutations in the a-galactosidase A gene accumulate globotriaosylceramide and become symptomatic in childhood with pain, gastrointestinal disturbances, angiokeratoma, and hypohidrosis. Classical patients experience progressive loss of renal function and hypertrophic cardiomyopathy, with severe clinical events including end-stage renal disease, stroke, arrhythmias, and premature death. The pathophysiological mechanisms by which endothelial cells, podocytes, smooth muscle cells, and tubular dysfunction occur in Fabry disease are poorly characterized and understood. This review evaluates the new evidence in pathophysiology of Fabry nephropathy, highlighting the necessity of early identification of individuals with Fabry disease. Keywords Fabry disease, globotriaosylceramide, podocyte, nitric oxide, angiotensin II Introduction of Gl3 in the endothelium and within the arterial wall, mainly in smooth muscle cells. This Gl3 and lyso-Gl3 accumulation Fabry disease is an X-linked genetic disorder of glycosphingo- in the endothelium leads to a secondary decrease in nitric lipid catabolism resulting from deficient activity of the lysoso- oxide (NO) synthesis and a trend to microthrombotic events mal enzyme a-galactosidase A (a-gal A). As a consequence, that lead to local ischemic events. In this regard, 2 primary the substrates of a-gal A, which are neutral glycosphingolipids, hypotheses have emerged to explain the pathogenesis of this mainly globotriaosylceramide (Gl3) and lyso-Gl3, accumulate vasculopathy.