DOCSLIB.ORG

Interactions of Ceramides and Proteins

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Interactions of Ceramides and Proteins OH OH OH OH O O O O O O NHAc OH C H HO OH OH 17 35 O O O NH AcHN CO2H O O HO OH HO O C13H27 OH O HO O CO H OH 2 HO HO O CO2H AcHN O HO AcHN HO CO2H HO OH O HO OH OH AcHN HO N E W S L E T T E R F OH R G L Y C O / S P H I N G O L I P I D R E S E A R C H J A N U A R Y 2 0 1 9 Interactions of Ceramides and Proteins Ceramides, ubiquitous sphingolipid interme- diates with multiple physiological functions, often ert their powerful effects by direct interactions w proteins. Identified ceramide-binding proteins incl the ceramide transfer protein CERT, the kinase sup- pressor of Ras, protein kinase c-Raf, cathepsin D, ex- ith protein phosphatase 2A inhibitor SET, and StarD7. O ude By manipulating specific cardiac ceramide-binding O proteins, researchers were able to reverse ceramide O HN induced lipotoxic cardiomyopathy. HO (1) In addition to ceramides forming lose c OH D2 plexes with proteins, ceramides have(2) been found to C C CD - D C 3 be attached, through ester linkages, to various pro 2 N-(32-Linoleoyloxy-dotriacontanoyl)-sphingosine-D9D2 teins of the cornified cell envelope of the skin. D om- ing protein envelope assembly, the membrane is con- Cat.# 2208 verted to a layer of ceramides covalently bound to 2. S. Walls et al. Ceramide-Protein Interactions protein envelope on the extracellular surface. It i - ur- Modulate Ceramide-Associated Lipotoxic Car- thought that the ester-linked ceramides constitute diomyopathy. Cell Rep. 22(10), 2702-2715 hydrophobic surface that functions as a water barri (2018) layer.(3) the 3. L. Marekov and P. Steinert. Ceramides are s a bound to structural proteins of the human fore- References: skin epidermal cornified cell envelope. J Biol er 1. S. Bockelmann et al. A search for ceramide bind- Chem. 273(28), 17763-17770 (1998) ing proteins using bifunctional lipid analogs yield CERT-related protein StarD7. J Lipid Res 59(3), 530 (2018) s Please visit www.matreya.com for a full list of INSIDE THIS high purity ceramide standards • ISSUE Interactions of Ceramides and Proteins •Sulfatides in Metochromatic Leukodystrophy 1 2-3 Matreya Newsletter Page 2 Sulfatides in Metachromatic Leukodystrophy Deuterated Biotinylated lyso HIGH PURITY Natural Fluorescent SULFATIDES Glycinated Well Defined Fatty Acids Sulfated Lactosylceramide Sulfatides are 3-sulfated galactosylceramides in lysosomes. (1) Metachromatic leukodystrophy is an that are found primarily in the central nervous system autosomal-recessive lysosomal storage disease caused and are myelin specific sphingolipids. Over the last by mutations in the arylsulfatase A (ARSA) gene several decades sulfatides have been linked to many leading to ARSA deficiency and causing sulfatide physiological functions and recently there has been a accumulation. Main symptoms of the disease are pro- renewed interest in their role in diseases. Sulfatides gressive demyelination, neurological dysfunction, and are highly multifunctional glycolipids involved in the reduced life expectancy. (2) A comparative study ana- nervous system, diabetes, immune system, hemosta- lyzing sulfatide levels in newborn urine and dried sis/thrombosis, bacterial infection, and viral infection. blood spot samples concluded that urine, but not dried By understanding the correlation between sulfatide’s blood spots, were useful for screening newborns for normal physiological functions and specific roles in metachromatic leukodystrophy. (3) disease, new diagnostic and therapeutic methods can Sulfatides are highly dynamic glycosphingol- be evaluated. ipids with far reaching biological processes. A greater Abnormal sulfatide metabolism, such as in understanding of these functions in living systems metachromatic leukodystrophy, can induce cell apop- will lead to the elucidation of associated diseases and tosis due to endosome-mediated ceramide generation the development of therapeutic treatments to various and the accumulation of cytotoxic levels of sulfatides sulfatide associated diseases. Matreya LLC, 2178 High Tech Road, State College, PA 16803 Tel: 800-342-3595 / 814-355-1030 Fax: 814-355-1031 www.matreya.com Matreya Newsletter Page 3 References: 1. X. Han et al. Endosomes and lysosomes play distinct roles in sulfatide-induced neuroblastoma apoptosis: potential mechanisms contributing to abnormal sulfatide metabolism in related neuronal diseases. Bio- chem. J. (2008) 410, 81 2. M. Manshadi et al., Four novel ARSA gene mutations with pathogenic impacts on metachromatic leu- kodystrophy: a bioinformatics approach to predict pathogenic mutations. Ther Clin Risk Manag. (2017) 13, 725-731 3. M. Barcenas et al. Quantification of sulfatides in dried blood and urine spots from metachromatic leu- kodystrophy patients by liquid chromatography/electrospray tandem mass spectrometry. Clinica Chimica Acta. 433, 39-43 (2014) O OH NH2 OH HN O HO3SO O OH OH N-Glycinated lyso -sulfatide (MS standard for lyso -sulfatide analysis) Cat. 2092 Product Name Catalog # Purity Sulfatides 1049 98+% lyso -Sulfatide 1904 98+% N-Glycinated lyso -sulfatide (MS standard for lyso ) 2092 98+% N-Acetyl-sulfatide (C2:0) 2076 98+% N-Dodecanoyl-sulfatide (C12:0) 1938 98+% N-Hexadecanoyl-sulfatide (C16:0) 1875 98+% N-Heptadecanoyl-sulfatide (C17:0) 1934 98+% N-Octadecanoyl-sulfatide (C18:0) 1932 98+% N-Octadecenoyl-(cis -9)-sulfatide (C18:1) 1933 98+% N-Nonadecanoyl-sulfatide (C19:0) 1935 98+% N-Tetracosanoyl-sulfatide (C24:0) 1888 98+% N-Tetracosenoyl-sulfatide (C24:1) 1931 98+% N-Hexanoyl-biotin-sulfatide 2207 98+% N-omega -CD 3-Octadecanoyl-sulfatide (deuterated) 1536 98+% N-Dodecanoyl-NBD-sulfatide (fluorescent) 1632 98+% N-Octadecanoyl-sulfated lactosylceramide 1540 98+% Matreya LLC, 2178 High Tech Road, State College, PA 16803 Tel: 800-342-3595 / 814-355-1030 Fax: 814-355-1031 www.matreya.com .
Load more

Recommended publications
  • Brain-Resident Immune Cells Responses As an Endogenous Stimulator in Myelin Sheath, Activates Inflammatory Sulfatide, a Major Li
    Sulfatide, A Major Lipid Component of Myelin Sheath, Activates Inflammatory Responses As an Endogenous Stimulator in Brain-Resident Immune Cells This information is current as of September 29, 2021. Sae-Bom Jeon, Hee Jung Yoon, Se-Ho Park, In-Hoo Kim and Eun Jung Park J Immunol 2008; 181:8077-8087; ; doi: 10.4049/jimmunol.181.11.8077 http://www.jimmunol.org/content/181/11/8077 Downloaded from References This article cites 44 articles, 16 of which you can access for free at: http://www.jimmunol.org/content/181/11/8077.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 29, 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 © 2008 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology Sulfatide, A Major Lipid Component of Myelin Sheath, Activates Inflammatory Responses As an Endogenous Stimulator in Brain-Resident Immune Cells1 Sae-Bom Jeon,*† Hee Jung Yoon,* Se-Ho Park,‡ In-Hoo Kim,2§ and Eun Jung Park2* Sulfatide, a major lipid component of myelin sheath, participates in diverse cellular events of the CNS, and its cellular level has recently been implicated in many inflammation-associated neuronal diseases.
    [Show full text]
  • A Myelin Galactolipid, Sulfatide, Is Essential for Maintenance of Ion Channels on Myelinated Axon but Not Essential for Initial Cluster Formation
    The Journal of Neuroscience, August 1, 2002, 22(15):6507–6514 A Myelin Galactolipid, Sulfatide, Is Essential for Maintenance of Ion Channels on Myelinated Axon But Not Essential for Initial Cluster Formation Tomoko Ishibashi,1,2,3 Jeffrey L. Dupree,4 Kazuhiro Ikenaka,1,3 Yukie Hirahara,5 Koichi Honke,6 Elior Peles,7 Brian Popko,8 Kinuko Suzuki,9 Hitoo Nishino,10 and Hiroko Baba2 1Department of Physiological Sciences, The Graduate University for Advanced Studies, Okazaki 444-8585, Japan, 2Department of Molecular Neurobiology, School of Pharmacy, Tokyo University of Pharmacy and Life Science, Hachioji 192-0392, Japan, 3Laboratory of Neural Information, National Institute for Physiological Sciences, Okazaki National Research Institutes, Okazaki 444-8585, Japan, 4Department of Pathology and Anatomy, Eastern Virginia Medical School, Norfolk, Virginia 23507, 5Research Institute, Osaka Medical Center for Maternal and Child Health, Izumi 594-1101, Japan, 6Department of Biochemistry, Osaka University Graduate School of Medicine, Suita 565-0871, Japan, 7Department of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot 76100, Israel, 8Neuroscience Center, Department of Biochemistry and Biophysics, Program in Molecular Biology and Biotechnology and 9Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, North Carolina 27599, and 10Department of Physiology, Nagoya City University Medical School, Nagoya 467-8601, Japan Myelinated axons are divided into four distinct regions: the served. Immunohistochemical analysis demonstrated a de- node of Ranvier, paranode, juxtaparanode, and internode, each crease in Na ϩ and K ϩ channel clusters, altered nodal length, of which is characterized by a specific set of axonal proteins. abnormal localization of K ϩ channel clusters appearing primar- Voltage-gated Na ϩ channels are clustered at high densities at ily in the presumptive paranodal regions, and diffuse distribu- the nodes, whereas shaker-type K ϩ channels are concentrated tion of contactin-associated protein along the internode.
    [Show full text]
  • (4,5) Bisphosphate-Phospholipase C Resynthesis Cycle: Pitps Bridge the ER-PM GAP
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by UCL Discovery Topological organisation of the phosphatidylinositol (4,5) bisphosphate-phospholipase C resynthesis cycle: PITPs bridge the ER-PM GAP Shamshad Cockcroft and Padinjat Raghu* Dept. of Neuroscience, Physiology and Pharmacology, Division of Biosciences, University College London, London WC1E 6JJ, UK; *National Centre for Biological Sciences, TIFR-GKVK Campus, Bellary Road, Bangalore 560065, India Address correspondence to: Shamshad Cockcroft, University College London UK; Phone: 0044-20-7679-6259; Email: [email protected] Abstract Phospholipase C (PLC) is a receptor-regulated enzyme that hydrolyses phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) at the plasma membrane (PM) triggering three biochemical consequences, the generation of soluble inositol 1,4,5-trisphosphate (IP3), membrane– associated diacylglycerol (DG) and the consumption of plasma membrane PI(4,5)P2. Each of these three signals triggers multiple molecular processes impacting key cellular properties. The activation of PLC also triggers a sequence of biochemical reactions, collectively referred to as the PI(4,5)P2 cycle that culminates in the resynthesis of this lipid. The biochemical intermediates of this cycle and the enzymes that mediate these reactions are topologically distributed across two membrane compartments, the PM and the endoplasmic reticulum (ER). At the plasma membrane, the DG formed during PLC activation is rapidly converted to phosphatidic acid (PA) that needs to be transported to the ER where the machinery for its conversion into PI is localised. Conversely, PI from the ER needs to be rapidly transferred to the plasma membrane where it can be phosphorylated by lipid kinases to regenerate PI(4,5)P2.
    [Show full text]
  • Antibacterial Activity of Ceramide and Ceramide Analogs Against
    www.nature.com/scientificreports OPEN Antibacterial activity of ceramide and ceramide analogs against pathogenic Neisseria Received: 10 August 2017 Jérôme Becam1, Tim Walter 2, Anne Burgert3, Jan Schlegel 3, Markus Sauer3, Accepted: 1 December 2017 Jürgen Seibel2 & Alexandra Schubert-Unkmeir1 Published: xx xx xxxx Certain fatty acids and sphingoid bases found at mucosal surfaces are known to have antibacterial activity and are thought to play a more direct role in innate immunity against bacterial infections. Herein, we analysed the antibacterial activity of sphingolipids, including the sphingoid base sphingosine as well as short-chain C6 and long-chain C16-ceramides and azido-functionalized ceramide analogs against pathogenic Neisseriae. Determination of the minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) demonstrated that short-chain ceramides and a ω-azido- functionalized C6-ceramide were active against Neisseria meningitidis and N. gonorrhoeae, whereas they were inactive against Escherichia coli and Staphylococcus aureus. Kinetic assays showed that killing of N. meningitidis occurred within 2 h with ω–azido-C6-ceramide at 1 X the MIC. Of note, at a bactericidal concentration, ω–azido-C6-ceramide had no signifcant toxic efect on host cells. Moreover, lipid uptake and localization was studied by fow cytometry and confocal laser scanning microscopy (CLSM) and revealed a rapid uptake by bacteria within 5 min. CLSM and super-resolution fuorescence imaging by direct stochastic optical reconstruction microscopy demonstrated homogeneous distribution of ceramide analogs in the bacterial membrane. Taken together, these data demonstrate the potent bactericidal activity of sphingosine and synthetic short-chain ceramide analogs against pathogenic Neisseriae. Sphingolipids are composed of a structurally related family of backbones termed sphingoid bases, which are sometimes referred to as ‘long-chain bases’ or ‘sphingosines’.
    [Show full text]
  • Role of Phospholipases in Adrenal Steroidogenesis
    229 1 W B BOLLAG Phospholipases in adrenal 229:1 R29–R41 Review steroidogenesis Role of phospholipases in adrenal steroidogenesis Wendy B Bollag Correspondence should be addressed Charlie Norwood VA Medical Center, One Freedom Way, Augusta, GA, USA to W B Bollag Department of Physiology, Medical College of Georgia, Augusta University (formerly Georgia Regents Email University), Augusta, GA, USA [email protected] Abstract Phospholipases are lipid-metabolizing enzymes that hydrolyze phospholipids. In some Key Words cases, their activity results in remodeling of lipids and/or allows the synthesis of other f adrenal cortex lipids. In other cases, however, and of interest to the topic of adrenal steroidogenesis, f angiotensin phospholipases produce second messengers that modify the function of a cell. In this f intracellular signaling review, the enzymatic reactions, products, and effectors of three phospholipases, f phospholipids phospholipase C, phospholipase D, and phospholipase A2, are discussed. Although f signal transduction much data have been obtained concerning the role of phospholipases C and D in regulating adrenal steroid hormone production, there are still many gaps in our knowledge. Furthermore, little is known about the involvement of phospholipase A2, Endocrinology perhaps, in part, because this enzyme comprises a large family of related enzymes of that are differentially regulated and with different functions. This review presents the evidence supporting the role of each of these phospholipases in steroidogenesis in the Journal Journal of Endocrinology adrenal cortex. (2016) 229, R1–R13 Introduction associated GTP-binding protein exchanges a bound GDP for a GTP. The G protein with GTP bound can then Phospholipids serve a structural function in the cell in that activate the enzyme, phospholipase C (PLC), that cleaves they form the lipid bilayer that maintains cell integrity.
    [Show full text]
  • The Role of Sulfatides in Disease
    O H 5 OH OH C17 3 O H H OH OH O O N H O OH O C13 27 O NHAc O O O O OH HO OH HO O OH HO O H CO2 H O CO2 O AcHN H HO O O OH AcHN 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 NEWSLETTER FOR GLYCO/SPHINGOLIPID RESEARCH FEBRUARY 2018 The Role of Sulfatides in Disease O OH OH Sulfatides are 3-sulfated galactosyl- NH ceramides that are found primarily in the cen- O O Sulfatides HO3SO tral nervous system and are myelin specific OH Cat.# 1049 sphingolipids. Over the last several decades, OH sulfatides have been linked to many physio- logical functions and recently there has been a renewed interest in jury, subsets of NKT cells have opposing roles. (5) Type I NKT their role in diseases. Sulfatides are highly multifunctional gly- cells promote injury while sulfatide-reactive type II NKT cells colipids involved in the nervous system, diabetes, immune sys- protect against injury. CD1d activation of NKT cells is con- tem, hemostasis/thrombosis, and bacterial and viral infection. By served from mice to humans, so strategies to modify these proc- understanding the correlation between sulfatide’s normal physio- esses might be developed to treat patients with hepatic reperfu- logical functions and specific roles in disease, new diagnostic and sion injury. therapeutic methods can be evaluated. Abnormal sulfatide metabolism, such as in Metachro- Sulfatides derived from the brain and spinal cord can matic leukodystrophy, can induce cell apoptosis due to en- have saturated, unsaturated, and 2-hydroxy fatty acyl chains, the dosome-mediated ceramide generation and the accumulation of composition of which are vital to influencing its function.
    [Show full text]
  • Type II NKT Cell Agonist, Sulfatide, Is an Effective Adjuvant for Oral Heat-Killed Cholera Vaccines
    Article Type II NKT Cell Agonist, Sulfatide, Is an Effective Adjuvant for Oral Heat-Killed Cholera Vaccines Aqel Albutti 1,2,† , Stephanie Longet 1,† , Craig P. McEntee 1, Shauna Quinn 1, Alex Liddicoat 1, Cristiana Rîmniceanu 3, Nils Lycke 3, Lydia Lynch 1, Susanna Cardell 3 and Ed C. Lavelle 1,4,* 1 Adjuvant Research Group, School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, D02 R590 Dublin, Ireland; [email protected] (A.A.); [email protected] (S.L.); [email protected] (C.P.M.); [email protected] (S.Q.); [email protected] (A.L.); [email protected] (L.L.) 2 Department of Medical Biotechnology, College of Applied Medical Sciences, Qassim University, Buraydah 52571, Saudi Arabia 3 Department of Microbiology and Immunology, Institute of Biomedicine, University of Gothenburg, Box 435, 405 30 Gothenburg, Sweden; [email protected] (C.R.); [email protected] (N.L.); [email protected] (S.C.) 4 Centre for Research on Adaptative Nanostructures and Nanodevices & Advanced Materials Bio-Engineering Research Centre, Trinity College Dublin, D02 PN40 Dublin, Ireland * Correspondence: [email protected]; Tel.: +353-1-8962488 † These authors contributed equally. Abstract: Oral vaccination has the potential to offer a safer and more efficacious approach for protection against enteric pathogens than injection-based approaches, especially in developing countries. One key advantage is the potential to induce intestinal immune responses in addition to Citation: Albutti, A.; Longet, S.; systemic immunity. In general, antigen delivery via the oral route triggers weak immune responses or McEntee, C.P.; Quinn, S.; Liddicoat, immunological tolerance.
    [Show full text]
  • STA-601-Sphingomyelin-Assay-Kit.Pdf
    Introduction Phospholipids are important structural lipids that are the major component of cell membranes and lipid bilayers. Phospholipids contain a hydrophilic head and a hydrophobic tail which give the molecules their unique characteristics. Most phospholipids contain one diglyceride, a phosphate group, and one choline group. Sphingomyelin (ceramide phosphorylcholine) is a sphingolipid found in eukaryotic cell membranes and lipoproteins. Sphingomyelin usually consists of a ceramide and phosphorylcholine molecule where the ceramide core comprises of a fatty acid bonded via an amide bond to a sphingosine molecule. There is a polar head group which is either phosphphoethanolamine or phosphocholine. Sphingomyelin represents about 85% of all sphingolipids and makes up about 10-20% of lipids within the plasma membrane. Sphingomyelin is involved in signal transduction and is highly concentrated in the myelin sheath around many nerve cell axons. The plasma membranes of many cells are rich with sphingomyelin. Sphigolipids are synthesized in a pathway that originates in the ER and is completed in the Golgi apparatus. Many of their functions are done in the plasma membranes and endosomes. Sphingomyelin is converted to ceramide via sphingomyelinases. Ceramides have been implicated in signaling pathways that lead to apoptosis, differentiation and proliferation. Sphingomyelins have been implicated in the pathogenesis of atherosclerosis, inflammation, necrosis, autophagy, senescence, stress response as well as other signaling disease states. Niemann-Pick disease is an inherited disease where deficiency of sphingomyelinase activity results in sphingomyelin accumulating in cells, tissues, and fluids. Other sphingolipid diseases are Fabry disease, Gaucher disease, Tay-Sachs disease, Krabbe disease and Metachromatic leukodystrophy. Cell Biolabs’ Sphingomyelin Assay Kit is a simple fluorometric assay that measures the amount of sphingomyelin present in plasma or serum, tissue homogenates, or cell suspensions in a 96-well microtiter plate format.
    [Show full text]
  • Correction of Metachromatic Leukodystrophy in the Mouse Model by Transplantation of Genetically Modified Hematopoietic Stem Cells
    Research article Related Commentary, page 1108 Correction of metachromatic leukodystrophy in the mouse model by transplantation of genetically modified hematopoietic stem cells Alessandra Biffi,1 Michele De Palma,1 Angelo Quattrini,2 Ubaldo Del Carro,2 Stefano Amadio,2 Ilaria Visigalli,1 Maria Sessa,2 Stefania Fasano,3 Riccardo Brambilla,3 Sergio Marchesini,4 Claudio Bordignon,1,5 and Luigi Naldini1,5 1San Raffaele Telethon Institute for Gene Therapy; 2Neurology Department; 3Department of Molecular Biology and Functional Genomics, San Raffaele Scientific Institute, Milan, Italy. 4Department of Biomedical Science and Biotechnology, University of Brescia, Brescia, Italy. 5Vita Salute San Raffaele University, Milan Italy. Gene-based delivery can establish a sustained supply of therapeutic proteins within the nervous system. For diseases characterized by extensive CNS and peripheral nervous system (PNS) involvement, widespread dis- tribution of the exogenous gene may be required, a challenge to in vivo gene transfer strategies. Here, using lentiviral vectors (LVs), we efficiently transduced hematopoietic stem cells (HSCs) ex vivo and evaluated the potential of their progeny to target therapeutic genes to the CNS and PNS of transplanted mice and correct a neurodegenerative disorder, metachromatic leukodystrophy (MLD). We proved extensive repopulation of CNS microglia and PNS endoneurial macrophages by transgene-expressing cells. Intriguingly, recruitment of these HSC-derived cells was faster and more robust in MLD mice. By transplanting HSCs transduced with the aryl- sulfatase A gene, we fully reconstituted enzyme activity in the hematopoietic system of MLD mice and pre- vented the development of motor conduction impairment, learning and coordination deficits, and neu- ropathological abnormalities typical of the disease.
    [Show full text]
  • Metabolism of Brain Glycolipid Fatty Acids '': Yasuo Kishimoto and Norman S
    Metabolism of Brain Glycolipid Fatty Acids '': Yasuo Kishimoto and Norman S. Radin, Mental Health Research Institute, University of Michigan, Ann Arbor, Michigan ABSTRACT and sulfatides contain NFA and tIFA, The metabolism of the fatty acid moieties saturated and unsaturated; the gangliosides, of brain cerebrosides, sulfatides, and however, contain only NFA in which there are gangliosides is reviewed and discussed. only traces of unsaturated acids. In the cere- The methodology involved in the isolation t)rosides and sulfatides there are two clusters of the fatty acids is described briefly. It of FA: those around 18 carbons long and those seems clear now that most of these acids around 24 carbons long. In the gangliosides are made by chain elongation of inter- there is only one cluster, centering around 18:0, mediate length fatty acids by addition of with negligible amounts of 22:0 and 24:0. acetate residues. The unsaturated acids Other points of contrast between gangliosides are made by desaturation of the inter- and the other two can be made: the former mediate length acids (palmitic, heptade- occurs primarily in brain gray matter, the canoic, stearic) followed by chain elonga- latter are primarily in white. The former tion. The hydroxy acids are made directly has glucose attached to the ceramide residue, from the corresponding nonhydroxy acids, the latter have galactose. The former has saturated, unsaturated, and odd-numbered. only traces of odd-numbered FA; the latter All the hydroxy acids undergo oxidative can contain considerable amounts of C~ and decarboxylation to yield fatty acids con- C2.~ FA. Further differences, particularly in taining one less carbon atom.
    [Show full text]
  • The Role of Fatty Acids in Ceramide Pathways and Their Influence On
    International Journal of Molecular Sciences Review The Role of Fatty Acids in Ceramide Pathways and Their Influence on Hypothalamic Regulation of Energy Balance: A Systematic Review Andressa Reginato 1,2,3,*, Alana Carolina Costa Veras 2,3, Mayara da Nóbrega Baqueiro 2,3, Carolina Panzarin 2,3, Beatriz Piatezzi Siqueira 2,3, Marciane Milanski 2,3 , Patrícia Cristina Lisboa 1 and Adriana Souza Torsoni 2,3,* 1 Biology Institute, State University of Rio de Janeiro, UERJ, Rio de Janeiro 20551-030, Brazil; [email protected] 2 Faculty of Applied Science, University of Campinas, UNICAMP, Campinas 13484-350, Brazil; [email protected] (A.C.C.V.); [email protected] (M.d.N.B.); [email protected] (C.P.); [email protected] (B.P.S.); [email protected] (M.M.) 3 Obesity and Comorbidities Research Center, University of Campinas, UNICAMP, Campinas 13083-864, Brazil * Correspondence: [email protected] (A.R.); [email protected] (A.S.T.) Abstract: Obesity is a global health issue for which no major effective treatments have been well established. High-fat diet consumption is closely related to the development of obesity because it negatively modulates the hypothalamic control of food intake due to metaflammation and lipotoxicity. The use of animal models, such as rodents, in conjunction with in vitro models of hypothalamic cells, can enhance the understanding of hypothalamic functions related to the control of energy Citation: Reginato, A.; Veras, A.C.C.; balance, thereby providing knowledge about the impact of diet on the hypothalamus, in addition Baqueiro, M.d.N.; Panzarin, C.; to targets for the development of new drugs that can be used in humans to decrease body weight.
    [Show full text]
  • Generation of Sphingosine-1-Phosphate Is Enhanced in Biliary Tract Cancer Patients and Is Associated with Lymphatic Metastasis
    www.nature.com/scientificreports OPEN Generation of sphingosine- 1-phosphate is enhanced in biliary tract cancer patients and Received: 5 April 2018 Accepted: 4 July 2018 is associated with lymphatic Published: xx xx xxxx metastasis Yuki Hirose1, Masayuki Nagahashi1, Eriko Katsuta2, Kizuki Yuza1, Kohei Miura1, Jun Sakata1, Takashi Kobayashi1, Hiroshi Ichikawa1, Yoshifumi Shimada1, Hitoshi Kameyama1, Kerry-Ann McDonald2, Kazuaki Takabe 1,2,3,4,5 & Toshifumi Wakai1 Lymphatic metastasis is known to contribute to worse prognosis of biliary tract cancer (BTC). Recently, sphingosine-1-phosphate (S1P), a bioactive lipid mediator generated by sphingosine kinase 1 (SPHK1), has been shown to play an important role in lymphangiogenesis and lymph node metastasis in several types of cancer. However, the role of the lipid mediator in BTC has never been examined. Here we found that S1P is elevated in BTC with the activation of ceramide-synthetic pathways, suggesting that BTC utilizes SPHK1 to promote lymphatic metastasis. We found that S1P, sphingosine and ceramide precursors such as monohexosyl-ceramide and sphingomyelin, but not ceramide, were signifcantly increased in BTC compared to normal biliary tract tissue using LC-ESI-MS/MS. Utilizing The Cancer Genome Atlas cohort, we demonstrated that S1P in BTC is generated via de novo pathway and exported via ABCC1. Further, we found that SPHK1 expression positively correlated with factors related to lymphatic metastasis in BTC. Finally, immunohistochemical examination revealed that gallbladder cancer with lymph node metastasis had signifcantly higher expression of phospho-SPHK1 than that without. Taken together, our data suggest that S1P generated in BTC contributes to lymphatic metastasis. Biliary tract cancer (BTC), the malignancy of the bile ducts and gallbladder, is a highly lethal disease in which a strong prognostic predictor is lymph node metastasis1–5.
    [Show full text]