Phospholipids at the Interface: Current Trends and Challenges
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Elimination of GPI2 Suppresses Glycosylphosphatidylinositol Glcnac
bioRxiv preprint doi: https://doi.org/10.1101/2021.03.18.436003; this version posted March 19, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Elimination of GPI2 suppresses glycosylphosphatidylinositol GlcNAc transferase activity and alters GPI glycan modification in Trypanosoma brucei Aurelio Jenni‡§, SeBastian Knüsel¶, Rupa Nagar||, Mattias Benninger¶, RoBert Häner**, Michael A. J. Ferguson||, IsaBel Roditi¶, Anant K. Menon#, Peter Bütikofer‡1 From the ‡Institute of Biochemistry and Molecular Medicine, University of Bern, 3012 Bern, Switzerland, the §Graduate School for Chemical and Biomedical Sciences, University of Bern, 3012 Bern, Switzerland, the ¶Institute of Cell Biology, University of Bern, 3012 Bern, Switzerland, the ||Wellcome Centre for Anti-Infectives Research, School of Life Sciences, University of Dundee, Dow Street, Dundee, United Kingdom, the **Department for Chemistry and Biochemistry, University of Bern, 3012 Bern, Switzerland, the #Department of Biochemistry, Weill Cornell Medical College, New York, New York 10065, USA. Running Title: GPI synthesis in the absence of GPI2 * The work was supported By Swiss National Science Foundation Sinergia grant CRSII5_170923 to RH, AKM and PB, by a Wellcome Tust Investigator Award (101842/Z13/Z) to MAJF and Swiss National Science Foundation grant 310030_184669 to IR. The authors declare that they have no conflicts of interest with the contents of this article. 1 To whom correspondence should Be addressed: Institute of Biochemistry and Molecular Medicine, Bühlstrasse 28, 3012 Bern, Switzerland. Tel.: 41-31-631-4113; E-mail: [email protected] 1 bioRxiv preprint doi: https://doi.org/10.1101/2021.03.18.436003; this version posted March 19, 2021. -
Role of Citicoline in the Management of Traumatic Brain Injury
pharmaceuticals Review Role of Citicoline in the Management of Traumatic Brain Injury Julio J. Secades Medical Department, Ferrer, 08029 Barcelona, Spain; [email protected] Abstract: Head injury is among the most devastating types of injury, specifically called Traumatic Brain Injury (TBI). There is a need to diminish the morbidity related with TBI and to improve the outcome of patients suffering TBI. Among the improvements in the treatment of TBI, neuroprotection is one of the upcoming improvements. Citicoline has been used in the management of brain ischemia related disorders, such as TBI. Citicoline has biochemical, pharmacological, and pharmacokinetic characteristics that make it a potentially useful neuroprotective drug for the management of TBI. A short review of these characteristics is included in this paper. Moreover, a narrative review of almost all the published or communicated studies performed with this drug in the management of patients with head injury is included. Based on the results obtained in these clinical studies, it is possible to conclude that citicoline is able to accelerate the recovery of consciousness and to improve the outcome of this kind of patient, with an excellent safety profile. Thus, citicoline could have a potential role in the management of TBI. Keywords: CDP-choline; citicoline; pharmacological neuroprotection; brain ischemia; traumatic brain injury; head injury Citation: Secades, J.J. Role of 1. Introduction Citicoline in the Management of Traumatic brain injury (TBI) is among the most devastating types of injury and can Traumatic Brain Injury. result in a different profile of neurological and cognitive deficits, and even death in the most Pharmaceuticals 2021, 14, 410. -
Suramin Alters Phosphoinositide Synthesis and Inhibits Growth Factor Receptor Binding in HT-29 Cells'
(CANCER RESEARCH 50. 6490-6496. October 15. 1990] Suramin Alters Phosphoinositide Synthesis and Inhibits Growth Factor Receptor Binding in HT-29 Cells' Reinhard Kopp2 and Andreas Pfeiffer Departments of Surgery and Internal Medicine II, Klinikum (irosshadern. University of Munich, West Germany ABSTRACT levels and a stimulation of calcium/calmodulin kinases. Di acylglycerol activates protein kinase C, a family of Ca2+-sensi- Initiation of cell growth frequently involves activation of growth factor tive and phospholipid-dependent isoenzymes, known to phos- receptor-coupled u rosine kinases and stimulation of the phosphoinositide phorylate regulatory proteins and to elevate cytosolic pH levels second messenger system. The antitrypanosomal and antifiliarial drug suramin has been shown to exert antiproliferative activities by inhibition (5, 6). Activation of protein kinase C by phorbol esters and of growth factor receptor binding. We therefore investigated the effect of elevation of intracellular calcium levels by calcium ionophores suramin on epidermal growth factor receptor-binding characteristics and, have been shown to be mitogenically active cofactors during the additionally, searched for effects on basal or cholinergically stimulated initiation of DNA synthesis (7-10). phospholipid metabolism in HT-29 cells. HT-29 colon carcinoma cells have recently been shown to Suramin caused a dose-dependent and noncompetitive inhibition of produce EGF/transforming growth factor «and insulin-like '"I-epidermal growth factor binding (concentration producing 50% inhi growth factor 1-like activities (11), indicating a possible auto bition, 44.2 Mg/ml)but did not alter muscarinic receptor binding. Suramin did not affect the basal '-'I* incorporation into phosphoinositides at crine proliferative effect of these growth factors. -
Nuclear Magnetic Resonance Spin Lattice Relaxation in Lecithin Reverse Micelles
Biosci., Vol. 4, Number 4, December 1982, pp. 449-454. © Printed in India. 31 [ P] -Nuclear magnetic resonance spin lattice relaxation in lecithin reverse micelles V. V. KUMAR, P. T. MANOHARAN and P. RAGHUNATHAN Department of Chemistry, Indian Institute of Technology, Kanpur 208 016 Regional Sophisticated Instrumentation Centre, Indian Institute of Technology, Madras 600 036 MS received 25 March 1982; revised 5 June 1982 31 Abstract. [ P] -Nuclear magnetic resonance (NMR) spin lattice relaxation times (T1) have been measured for lecithin-nonpolar solvent-water as a function of added water for three solvents, namely, benzene, carbon tetrachloride and cyclohexane. In benzene and carbon 31 tetrachloride systems, where spherical reverse micelles are formed, [ P]-NMR T1, values 31 increase linearly with added water. However, in cyclohexane, the trends in the [ P]-T1 values indicate very different micellisation processes. Even at the lowest concentration of added 31 water, the [ P]-T1 values in this solvent are substantially larger than the corresponding values in benzene and carbon tetrachloride, which is attributed to the intramolecular chlorine- phosphate interaction being the weakest in cyclohexane. At a higher water content of six 31 mols of water per mol of lecithin in cyclohexane solvent, the [ Ρ]-T1 values show a sharp decrease indicating a sudden change in the dynamics of the phosphate group, and this confirms the on set of 'reverse micelle-to-liquid crystalline' phase transition observed in this system by other spectroscopic and physical techniques. Keywords. [31P]-NMR; spin lattice relaxation; lecithin reverse micelles. Introduction There has been a rapid growth of interest in recent years in the study of phospholipid aggregates in nonpolar media since these aggregated structures often ‘model’ faithfully the nature of cell membranes. -
(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. -
Synthesis of Lysophospholipids
Molecules 2010, 15, 1354-1377; doi:10.3390/molecules15031354 OPEN ACCESS molecules ISSN 1420-3049 www.mdpi.com/journal/molecules Review Synthesis of Lysophospholipids Paola D’Arrigo 1,2,* and Stefano Servi 1,2 1 Dipartimento di Chimica, Materiali ed Ingegneria Chimica “Giulio Natta”, Politecnico di Milano, Via Mancinelli 7, 20131 Milano, Italy 2 Centro Interuniversitario di Ricerca in Biotecnologie Proteiche "The Protein Factory", Politecnico di Milano and Università degli Studi dell'Insubria, Via Mancinelli 7, 20131 Milano, Italy * Author to whom correspondence should be addressed; E-Mail: paola.d’[email protected]. Received: 17 February 2010; in revised form: 4 March 2010 / Accepted: 5 March 2010 / Published: 8 March 2010 Abstract: New synthetic methods for the preparation of biologically active phospholipids and lysophospholipids (LPLs) are very important in solving problems of membrane–chemistry and biochemistry. Traditionally considered just as second-messenger molecules regulating intracellular signalling pathways, LPLs have recently shown to be involved in many physiological and pathological processes such as inflammation, reproduction, angiogenesis, tumorogenesis, atherosclerosis and nervous system regulation. Elucidation of the mechanistic details involved in the enzymological, cell-biological and membrane-biophysical roles of LPLs relies obviously on the availability of structurally diverse compounds. A variety of chemical and enzymatic routes have been reported in the literature for the synthesis of LPLs: the enzymatic transformation of natural glycerophospholipids (GPLs) using regiospecific enzymes such as phospholipases A1 (PLA1), A2 (PLA2) phospholipase D (PLD) and different lipases, the coupling of enzymatic processes with chemical transformations, the complete chemical synthesis of LPLs starting from glycerol or derivatives. In this review, chemo- enzymatic procedures leading to 1- and 2-LPLs will be described. -
Acetylcholine Signaling System in Progression of Lung Cancers
Pharmacology & Therapeutics 194 (2019) 222–254 Contents lists available at ScienceDirect Pharmacology & Therapeutics journal homepage: www.elsevier.com/locate/pharmthera Acetylcholine signaling system in progression of lung cancers Jamie R. Friedman a,1, Stephen D. Richbart a,1,JustinC.Merritta,KathleenC.Browna, Nicholas A. Nolan a, Austin T. Akers a, Jamie K. Lau b, Zachary R. Robateau a, Sarah L. Miles a,PiyaliDasguptaa,⁎ a Department of Biomedical Sciences, Joan C. Edwards School of Medicine, 1700 Third Avenue, Huntington, WV 25755 b Biology Department, Center for the Sciences, Box 6931, Radford University, Radford, Virginia 24142 article info abstract Available online 3 October 2018 The neurotransmitter acetylcholine (ACh) acts as an autocrine growth factor for human lung cancer. Several lines of evidence show that lung cancer cells express all of the proteins required for the uptake of choline (choline Keywords: transporter 1, choline transporter-like proteins) synthesis of ACh (choline acetyltransferase, carnitine acetyl- Lung cancer transferase), transport of ACh (vesicular acetylcholine transport, OCTs, OCTNs) and degradation of ACh (acetyl- Acetylcholine cholinesterase, butyrylcholinesterase). The released ACh binds back to nicotinic (nAChRs) and muscarinic Cholinergic receptors on lung cancer cells to accelerate their proliferation, migration and invasion. Out of all components Proliferation of the cholinergic pathway, the nAChR-signaling has been studied the most intensely. The reason for this trend Invasion Anti-cancer drugs is due to genome-wide data studies showing that nicotinic receptor subtypes are involved in lung cancer risk, the relationship between cigarette smoke and lung cancer risk as well as the rising popularity of electronic ciga- rettes considered by many as a “safe” alternative to smoking. -
Activation by Inhibition of Second Messenger Compounds
1230 Annals ofthe Rheumatic Diseases 1992; 51: 1230-1236 Sulphasalazine inhibition of human granulocyte Ann Rheum Dis: first published as 10.1136/ard.51.11.1230 on 1 November 1992. Downloaded from activation by inhibition of second messenger compounds Gunnar Carlin, Richard Djursater, Goran Smedegard Abstract We have previously found by using the The effects of sulphasalazine on the pro- granulocyte as a model system that sulpha- duction of second messenger compounds in salazine inhibits cellular activation before activa- human granulocytes have been characterised tion of protein kinase C by interference with the by various stimuli. The increases in cytosolic synthesis of phosphoinositide derived second calcium, inositol trisphosphate, diacylgly- messenger compounds.6 As several cell types cerol, and phosphatidic acid (all important utilise phosphoinositide dependent signal trans- mediators of intracellular signal transduction) duction, sulphasalazine may modify a principal triggered by stimulation were inhibited by common mechanism for the regulation of sulphasalazine. The metabolites 5-amino- cell activity, which may explain the beneficial salicylic acid and sulphapyridine were less effects of the drug in a variety of diseases. potent inhibitors than the mother compound. Many of the stimuli used in the earlier studies It is concluded that sulphasalazine inhibits trigger an increase in cytosolic calcium as part of the synthesis of phosphoinositide derived the activation sequence. The increase in calcium second messenger compounds at the level of has, in a variety of cell systems, been found to phospholipase C or its regulatory guanosine depend on remodelling of phosphoinositides'3 5'-triphosphate (GTP) binding protein. In- (see fig 1). Ligation of a cell receptor leads to hibition of phosphatidic acid synthesis was the phospholipase C dependent hydrolysis of either due to the same mechanism, or to phosphatidylinositol-4,5-bisphosphate genera- interaction with a phospholipase D regulating ting two triggers of cell responses, namely GTP binding protein. -
Alpha-GPC Introduced 2003
Product Information Sheet – January 2015 Alpha-GPC Introduced 2003 What Is It? Are There Any Potential Drug Interactions? l-Alpha-glycerophophatidylcholine (GPC-choline, alpha-GPC) is a water- At this time, there are no known adverse reactions when taken in soluble phospholipid and neurotransmitter precursor naturally conjunction with medications. occurring in the body. Unlike most membrane phospholipids, alpha- GPC is water-soluble because it lacks the hydrophobic tail groups. Alpha-GPC Uses For Alpha-GPC each Caplique® Capsule contains v 0 • Memory And Cognitive Health: Alpha-GPC passes through the alpha-GPC (L-alpha-glycerophosphatidylcholine) ........................ 200 mg blood brain barrier providing a source of choline for acetylcholine other ingredients: glycerin, water, vegetarian Caplique® Capsule (cellulose, water) and phosphatidylcholine biosynthesis. By supporting cell membrane fluidity and integrity, phosphatidylcholine enhances Contains soy healthy neurotransmitter function and signal transduction. 6 Caplique® Capsules daily, in divided doses, with or Alpha-GPC may support healthy phospholipid turnover in the between meals. brain, helping to counteract age-related cellular breakdown of membrane phospholipids. Acetylcholine is a key neurotransmitter Caplique® Capsule is a registered trademark used by Pure Encapsulations in the brain supporting memory and learning. Optimal under license. phospholipid and acetylcholine levels support cognitive, mental Each Caplique® Capsule is preserved with a nitrogen bubble, which may give the and cerebrovascular health.* appearance of the capsule not being full. Contents may appear cloudy or thick and • Growth Hormone Support: Alpha-GPC has the ability to may settle or separate. potentiate growth hormone releasing hormone (GHRH), thereby supporting healthy growth hormone (GH) levels. The mechanism of support appears to involve increased cholinergic tone.* What Is The Source? Alpha-GPC is derived from highly purified soy lecithin. -
Identification of a Phosphatidic Acid-Preferring Phospholipase Al
Proc. Nati. Acad. Sci. USA Vol. 91, pp. 9574-9578, September 1994 Biochemistry Identification of a phosphatidic acid-preferring phospholipase Al from bovine brain and testis (lysophosphatidic acld/lysophosphoipase/Triton X-100 miceles/phospholpase D/diacylgycerol kinase) HENRY N. HIGGS AND JOHN A. GLOMSET* Departments of Biochemistry and Medicine and Regional Primate Research Center, Howard Hughes Medical Institute, University of Washington, SL-15, Seattle, WA 98195 Contributed by John A. Glomset, May 31, 1994 ABSTRACT Recent experiments in several laboratories drolysis by phospholipase A (PLA) activities, producing have provided evidence that phosphatidic acid functions in cell lysophosphatidic acid (LPA). A PA-specific PLA2 has been signaling. However, the mechaninsm that regulate cellular reported (16), but detailed information about this enzyme is phosphatidic acid levels remain obscure. Here we describe a lacking. Another possibility is that a PLA1 might metabolize soluble phospholipase Al from bovine testis that preferentially PA to sn-2-LPA. Several PLA1 activities have been identified hydrolyzes phosphatidic acid when assayed in Triton X-100 in mammalian tissues, including one found in rat liver plasma micelles. Moreover, the enzyme hydrolyzes phosphatidic acid membrane (17), another found in rat brain cytosol (18, 19), molecular species containing two unsaturated fatty acids in and others found in lysosomes (20, 21). None of these preference to those containing a combination of saturated and enzymes, however, displays a preference for PA as a sub- unsaturated fatty acyl groups. Under certain conditions, the strate. enzyme also displays lysophospholipase activity toward In the present study, we identify and characterize a cyto- lysophosphatidic acid. The phospholipase Al is not likely to be solic PLA1 with a strong preference for PA. -
Dissociation of Inositol Trisphosphate from Diacylglycerol Production in Rous Sarcoma Virus-Transformed Fibroblasts Timothy J
Dissociation of Inositol Trisphosphate from Diacylglycerol Production in Rous Sarcoma Virus-transformed Fibroblasts Timothy J. Martins, Yoshikazu Sugimoto, and R. L. Erikson Department of Cellular and Developmental Biology, Harvard University, Cambridge, Massachusetts 02138 Abstract. The metabolism of phosphatidylinositol (PI) changes intermediate between those of transformed and and related intermediates was studied in uninfected nontransformed cells. NY72-4 CEF exhibited no in- and Rous sarcoma virus-(RSV) infected chicken em- crease in phosphoinositol concentrations before 8 h in- bryo fibroblasts (CEFs). Cells infected with wild-type cubation at 35°C, indicating that the transformation- Downloaded from http://rupress.org/jcb/article-pdf/108/2/683/1057290/683.pdf by guest on 26 September 2021 RSV exhibited twofold increases in steady-state con- specific changes in inositol metabolism were a delayed centrations of inositol trisphosphate (IP3) and inositol event. Furthermore, inositol turnover was not activated bisphosphate (IP2) as compared to uninfected CEFs. In during this time. In contrast to the case of inositol me- addition, increased concentrations of IP3 and IP2 were tabolism, significant increases in diacylglycerol (DAG) observed in CEFs infected with the RSV temperature- concentrations were observed within 15-30 min after sensitive transformation mutant NY72-4 when main- shift of NY72-4 CEFs to 35°C. tained at the permissive temperature (35°C) for >24 h. These findings suggest that (a) the major changes in Slight increases were -
Présentation Powerpoint
Table S1- List of metabolites analyzed with the AbsoluteIDQ p180 kit Metabolite Short name Biochemical Name Metabolite Short name Biochemical Name Class Class C0 L-Carnitine Ala Alanine C10 Decanoyl-L-carnitine Arg Arginine C10:1 Decenoyl-L-carnitine Asn Asparagine C10:2 Decadienyl-L-carnitine Asp Aspartate C12 Dodecanoyl-L-carnitine Cit Citrulline C12:1 Dodecenoyl-L-carnitine Gln Glutamine C12-DC Dodecanedioyl-L-carnitine Glu Glutamate C14 Tetradecanoyl-L-carnitine Gly Glycine C14:1 Tetradecenoyl-L-carnitine His Histidine C14:1-OH Hydroxytetradecenoyl-L-carnitine acids Ile Isoleucine C14:2 Tetradecadienyl-L-carnitine Leu Leucine C14:2-OH Hydroxytetradecadienyl-L-carnitine Lys Lysine C16 Hexadecanoyl-L-carnitine C16:1 Hexadecenoyl-L-carnitine Met Methionine C16:1-OH Hydroxyhexadecenoyl-L-carnitine Orn Ornithine C16:2 Hexadecadienyl-L-carnitine Amino Phe Phenylalanine C16:2-OH Hydroxyhexadecadienyl-L-carnitine Pro Proline Ser Serine carnitines C16-OH Hydroxyhexadecanoyl-L-carnitine - C18 Octadecanoyl-L-carnitine Thr Threonine L - C18:1 Octadecenoyl-L-carnitine Trp Tryptophan C18:1-OH Hydroxyoctadecenoyl-L-carnitine Tyr Tyrosine C18:2 Octadecadienyl-L-carnitine Val Valine acyl C2 Acetyl-L-carnitine Ac-Orn Acetylornithine C3 Propionyl-L-carnitine ADMA Asymmetric dimethylarginine & C3:1 Propenyl-L-carnitine SDMA Symmetric dimethylarginine C3-DC / C4-OH Malonyl-L-carnitine / Hydroxybutyryl-L- alpha-AAA alpha-Aminoadipic acid carnitine Carnosine Carnosine C3-DC-M / C5-OH Methylmalonyl-L-carnitine / Creatinine Creatinine Hydroxyvaleryl-L-carnitine