Genomes and Genes
Summary: An amino alcohol with a long unsaturated hydrocarbon chain. Sphingosine and its derivative sphinganine are the major bases of the sphingolipids in mammals. (Dorland, 28th ed)
Publications311 found, 100 shown here
- "Inside-out" signaling of sphingosine-1-phosphate: therapeutic targetsKazuaki Takabe
Department of Surgery, Division of Surgical Oncology, Virginia Commonwealth University School of Medicine, Richmond, VA 23298, USA
Pharmacol Rev 60:181-95. 2008b>Sphingosine 1-phosphate (S1P) is a bioactive sphingolipid metabolite involved in many critical cellular processes including proliferation, survival, and migration, as well as angiogenesis and allergic responses...
- Principles of bioactive lipid signalling: lessons from sphingolipidsYusuf A Hannun
Department of Biochemistry and Molecular Biology, Medical University of South Carolina, 173 Ashley Avenue, Charleston, South Carolina 29425, USA
Nat Rev Mol Cell Biol 9:139-50. 2008..The rapidly expanding field of bioactive lipids is exemplified by many sphingolipids, such as ceramide, sphingosine, sphingosine-1-phosphate (S1P), ceramide-1-phosphate and lyso-sphingomyelin, which have roles in the regulation ..
- A placebo-controlled trial of oral fingolimod in relapsing multiple sclerosisLudwig Kappos
Department of Neurology, University Hospital, University of Basel, Switzerland
N Engl J Med 362:387-401. 2010Oral fingolimod, a sphingosine-1-phosphate-receptor modulator that prevents the egress of lymphocytes from lymph nodes, significantly improved relapse rates and end points measured on magnetic resonance imaging (MRI), as compared with ..
- Oral fingolimod or intramuscular interferon for relapsing multiple sclerosisJeffrey A Cohen
Mellen Center, Cleveland Clinic, Cleveland, OH 44195, USA
N Engl J Med 362:402-15. 2010Fingolimod (FTY720), a sphingosine-1-phosphate-receptor modulator that prevents lymphocyte egress from lymph nodes, showed clinical efficacy and improvement on imaging in a phase 2 study involving patients with multiple sclerosis.
- Sphingosine-1-phosphate signaling and its role in diseaseMichael Maceyka
Department of Biochemistry and Molecular Biology, Massey Cancer Center, Virginia Commonwealth University School of Medicine, 1101 E Marshall Street, Richmond, VA 23298, USA
Trends Cell Biol 22:50-60. 2012The bioactive sphingolipid metabolite sphingosine-1-phosphate (S1P) is now recognized as a critical regulator of many physiological and pathophysiological processes, including cancer, atherosclerosis, diabetes and osteoporosis...
- Sphingosine-1-phosphate: an enigmatic signalling lipidSarah Spiegel
Department of Biochemistry, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, Virginia 23298 0614, USA
Nat Rev Mol Cell Biol 4:397-407. 2003The evolutionarily conserved actions of the sphingolipid metabolite, sphingosine-1-phosphate (S1P), in yeast, plants and mammals have shown that it has important functions...
- Lymphocyte egress from thymus and peripheral lymphoid organs is dependent on S1P receptor 1Mehrdad Matloubian
Howard Hughes Medical Institute and Department of Microbiology, University of California San Francisco, 513 Parnassus Avenue, San Francisco, California 94143 0414, USA
Nature 427:355-60. 2004..emigration from lymphoid organs, and phosphorylated FTY720 binds and activates four of the five known sphingosine-1-phosphate (S1P) receptors. However, the role of S1P receptors in normal immune cell trafficking is unclear...
- Sphingosine-1-phosphate and lymphocyte egress from lymphoid organsJason G Cyster
Howard Hughes Medical Institute and Department of Microbiology and Immunology, University of California, San Francisco, California 94143 0414, USA
Annu Rev Immunol 30:69-94. 2012Much has been learned about how cells enter lymphoid tissues. But how do they leave? Sphingosine-1-phosphate (S1P) has emerged over the past decade as a central mediator of lymphocyte egress...
- The immune modulator FTY720 targets sphingosine 1-phosphate receptorsVolker Brinkmann
Department of Transplantation, Novartis Pharma AG, Lichtstrasse 35, CH 4002 Basel, Switzerland
J Biol Chem 277:21453-7. 2002..Using FTY720 and several analogs, we show now that FTY720 is phosphorylated by sphingosine kinase; the phosphorylated compound is a potent agonist at four sphingosine 1-phosphate receptors and ..
- Fingolimod (FTY720): discovery and development of an oral drug to treat multiple sclerosisVolker Brinkmann
Department of Autoimmunity, Transplantation and Inflammation, Novartis Institutes for BioMedical Research, Novartis Campus Forum 1, WSJ 386, CH 4056 Basel, Switzerland
Nat Rev Drug Discov 9:883-97. 2010..Elucidation of the effects of fingolimod--mediated by the modulation of sphingosine 1-phosphate (S1P) receptors--has indicated that its therapeutic activity could be due to regulation of the ..
- Sphingosine-1-phosphate produced by sphingosine kinase 1 promotes breast cancer progression by stimulating angiogenesis and lymphangiogenesisMasayuki Nagahashi
Division of Surgical Oncology, Department of Biochemistry and Molecular Biology, and the Massey Cancer Center, Virginia Commonwealth University School of Medicine, Richmond, Virginia 23298, USA
Cancer Res 72:726-35. 2012b>Sphingosine-1-phosphate (S1P) is a pleiotropic bioactive lipid mediator that promotes breast cancer progression by diverse mechanisms that remain somewhat unclear...
- Identification of serum-derived sphingosine-1-phosphate as a small molecule regulator of YAPEric Miller
Genomics Institute of the Novartis Research Foundation, San Diego, CA 92121, USA
Chem Biol 19:955-62. 2012..Through chemical isolation and activity profiling, we identified serum-derived sphingosine-1-phosphate (S1P) and lysophosphatidic acid (LPA) as small molecule activators of YAP...
- Sphingosine 1-phosphate and cancerNigel J Pyne
Cell Biology Group, Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 27 Taylor Street, Glasgow G4 0NR, UK
Nat Rev Cancer 10:489-503. 2010There is substantial evidence that sphingosine 1-phosphate (S1P) is involved in cancer...
- FTY720 (fingolimod) efficacy in an animal model of multiple sclerosis requires astrocyte sphingosine 1-phosphate receptor 1 (S1P1) modulationJi Woong Choi
Department of Molecular Biology, Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, CA 92037, USA
Proc Natl Acad Sci U S A 108:751-6. 2011b>Sphingosine 1-phosphate (S1P), a lysophospholipid, has gained relevance to multiple sclerosis through the discovery of FTY720 (fingolimod), recently approved as an oral treatment for relapsing forms of multiple sclerosis...
- Lipid signalling in diseaseMatthias P Wymann
Institute of Biochemistry and Genetics, Department of Biomedicine, University of Basel, Mattenstrasse 28, CH 4058 Basel, Switzerland
Nat Rev Mol Cell Biol 9:162-76. 2008..of lipid-modifying enzymes: phospholipases, prostaglandin synthase, 5-lipoxygenase, phosphoinositide 3-kinase, sphingosine kinase and sphingomyelinase...
- Regulation of histone acetylation in the nucleus by sphingosine-1-phosphateNitai C Hait
Department of Biochemistry and Molecular Biology and the Massey Cancer Center, Virginia Commonwealth University School of Medicine, Richmond, VA 23298, USA
Science 325:1254-7. 2009The pleiotropic lipid mediator sphingosine-1-phosphate (S1P) can act intracellularly independently of its cell surface receptors through unknown mechanisms...
- Lymphocyte sequestration through S1P lyase inhibition and disruption of S1P gradientsSusan R Schwab
Howard Hughes Medical Institute and Department of Microbiology and Immunology, University of California San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143 0414, USA
Science 309:1735-9. 2005Lymphocyte egress from the thymus and from peripheral lymphoid organs depends on sphingosine 1-phosphate (S1P) receptor-1 and is thought to occur in response to circulatory S1P...
- Biologically active sphingolipids in cancer pathogenesis and treatmentBesim Ogretmen
Department of Biochemistry and Molecular Biology, and Hollings Cancer Center, 173 Ashley Avenue, Charleston, South Carolina 29425, USA
Nat Rev Cancer 4:604-16. 2004
- Oral fingolimod (FTY720) for relapsing multiple sclerosisLudwig Kappos
Department of Neurology, University Hospital, Basel, Switzerland
N Engl J Med 355:1124-40. 2006..Fingolimod (FTY720) is a new oral immunomodulating agent under evaluation for the treatment of relapsing multiple sclerosis...
- Niemann-Pick disease type C1 is a sphingosine storage disease that causes deregulation of lysosomal calciumEmyr Lloyd-Evans
Department of Pharmacology, University of Oxford, Mansfield Road, Oxford, UK
Nat Med 14:1247-55. 2008..The function of NPC1 is unknown, but when it is dysfunctional, sphingosine, glycosphingolipids, sphingomyelin and cholesterol accumulate...
- Lipopolysaccharide and sphingosine-1-phosphate cooperate to induce inflammatory molecules and leukocyte adhesion in endothelial cellsIsabel Fernández-Pisonero
Instituto de Biologia y Genetica Molecular, Consejo Superior de Investigaciones Científicas and Universidad de Valladolid, Valladolid 47003, Spain
J Immunol 189:5402-10. 2012Given that TLRs and sphingosine-1-phosphate (S1P) are key players in inflammation, we explored the potential interplay between TLRs and S1P in the adhesion/inflammatory pathways in primary human endothelial cells...
- GRK2-dependent S1PR1 desensitization is required for lymphocytes to overcome their attraction to bloodTal I Arnon
Howard Hughes Medical Institute and Department of Microbiology and Immunology, University of California San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143, USA
Science 333:1898-903. 2011Lymphocytes egress from lymphoid organs in response to sphingosine-1-phosphate (S1P); minutes later they migrate from blood into tissue against the S1P gradient...
- Acid ceramidase-mediated production of sphingosine 1-phosphate promotes prostate cancer invasion through upregulation of cathepsin BThomas H Beckham
Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC, USA
Int J Cancer 131:2034-43. 2012..Here, we demonstrate that AC, through generation of sphingosine-1-phosphate (S1P), promotes Ets1 nuclear expression and binding to the promoter region of matrix-degrading ..
- Sphingosine but not sphingosine-1-phosphate stimulates suicidal erythrocyte deathSyed M Qadri
Department of Physiology, University of Tubingen, Tubingen, Germany
Cell Physiol Biochem 28:339-46. 2011b>Sphingosine kinase 1 phosphorylates sphingosine, which is converted to ceramide by ceramide synthetase...
- Sphingosine-1-phosphate links persistent STAT3 activation, chronic intestinal inflammation, and development of colitis-associated cancerJie Liang
Department of Biochemistry and Molecular Biology and the Massey Cancer Center, Virginia Commonwealth University School of Medicine, Richmond, VA 23298, USA
Cancer Cell 23:107-20. 2013Inflammatory bowel disease is an important risk factor for colorectal cancer. We show that sphingosine-1-phosphate (S1P) produced by upregulation of sphingosine kinase 1 (SphK1) links chronic intestinal inflammation to colitis-associated ..
- The outs and the ins of sphingosine-1-phosphate in immunitySarah Spiegel
Department of Biochemistry and Molecular Biology and the Massey Cancer Center, Virginia Commonwealth University School of Medicine, Richmond, Virginia 23298, USA
Nat Rev Immunol 11:403-15. 2011The potent lipid mediator sphingosine-1-phosphate (S1P) is produced inside cells by two closely related kinases, sphingosine kinase 1 (SPHK1) and SPHK2, and has emerged as a crucial regulator of immunity...
- Sphingosine-1-phosphate is a missing cofactor for the E3 ubiquitin ligase TRAF2Sergio E Alvarez
Department of Biochemistry and Molecular Biology and the Massey Cancer Center, Virginia Commonwealth University School of Medicine, 1101 E Marshall Street, Richmond, Virginia 23298, USA
Nature 465:1084-8. 2010..TRAF2 binds to sphingosine kinase 1 (SphK1), one of the isoenzymes that generates the pro-survival lipid mediator sphingosine-1-phosphate (..
- Sphingosine 1-phosphate receptors in health and disease: mechanistic insights from gene deletion studies and reverse pharmacologyVolker Brinkmann
Autoimmunity and Transplantation, Novartis Institutes for BioMedical Research, Lichtstrasse 35, CH 4002 Basel, Switzerland
Pharmacol Ther 115:84-105. 2007b>Sphingosine 1-phosphate (S1P) is a bioactive sphingolipid that is critically involved in the embryonic development of the cardiovascular and central nervous systems...
- Mechanism of action of oral fingolimod (FTY720) in multiple sclerosisJerold Chun
Department of Molecular Biology, Helen L Dorris Child and Adolescent Neuropsychiatric Disorder Institute, The Scripps Research Institute, La Jolla, CA, USA
Clin Neuropharmacol 33:91-101. 2010..In vivo, fingolimod is phosphorylated to form fingolimod-phosphate, which resembles naturally occurring sphingosine 1-phosphate (S1P), an extracellular lipid mediator whose major effects are mediated by cognate G protein-..
- Endothelial functions of sphingosine-1-phosphateSusann Lucke
Institute of Pathophysiology, Universitatsklinikum Essen, Essen, Germany
Cell Physiol Biochem 26:87-96. 2010The biologically active sphingolipid sphingosine-1-phosphate (S1P) plays key functions in the immune, inflammatory, and cardiovascular systems...
- Sphingosine 1-phosphate promotes endothelial cell barrier integrity by Edg-dependent cytoskeletal rearrangementJ G Garcia
Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21224, USA
J Clin Invest 108:689-701. 2001..We assessed the participation of sphingosine 1-phosphate (Sph-1-P), a biologically active phosphorylated lipid growth factor released from activated ..
- Sphingosine analogue drug FTY720 targets I2PP2A/SET and mediates lung tumour suppression via activation of PP2A-RIPK1-dependent necroptosisSahar A Saddoughi
Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC, USA
EMBO Mol Med 5:105-21. 2013..Thus, these data suggest that targeting I2PP2A/SET by FTY720 suppresses lung tumour growth, at least in part, via PP2A activation and necroptosis mediated by the kinase domain of RIPK1...
- Edg-1, the G protein-coupled receptor for sphingosine-1-phosphate, is essential for vascular maturationY Liu
Genetics of Development and Disease Branch, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, Maryland 20892 1821, USA
J Clin Invest 106:951-61. 2000Sphingolipid signaling pathways have been implicated in many critical cellular events. Sphingosine-1-phosphate (SPP), a sphingolipid metabolite found in high concentrations in platelets and blood, stimulates members of the endothelial ..
- Promotion of lymphocyte egress into blood and lymph by distinct sources of sphingosine-1-phosphateRajita Pappu
Cardiovascular Research Institute, University of California, San Francisco, 600 16th Street S472D, San Francisco, CA 94143 2240, USA
Science 316:295-8. 2007Lymphocytes require sphingosine-1-phosphate (S1P) receptor-1 to exit lymphoid organs, but the source(s) of extracellular S1P and whether S1P directly promotes egress are unknown...
- Deregulation of sphingolipid metabolism in Alzheimer's diseaseXingxuan He
Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, NY 10029, USA
Neurobiol Aging 31:398-408. 2010..More sphingosine also was found in the AD brains, although sphingosine-1-phosphate (S1P) levels were reduced...
- Molecular cloning and functional characterization of a novel mammalian sphingosine kinase type 2 isoformH Liu
Department of Biochemistry and Molecular Biology, Georgetown University Medical Center, Washington, D C 20007, USA
J Biol Chem 275:19513-20. 2000b>Sphingosine-1-phosphate (SPP) has diverse biological functions acting inside cells as a second messenger to regulate proliferation and survival, and extracellularly, as a ligand for G protein-coupled receptors of the endothelial ..
- Sphingosine-1-phosphate receptor 3 promotes recruitment of monocyte/macrophages in inflammation and atherosclerosisPetra Keul
Institute for Pathophysiology, University Hospital Essen, Hufelandstrasse 55, 45122 Essen, Germany
Circ Res 108:314-23. 2011The role of sphingosine-1-phosphate (S1P) and its receptors in the pathogenesis of atherosclerosis has not been investigated.
- Transactivation of vascular endothelial growth factor (VEGF) receptor Flk-1/KDR is involved in sphingosine 1-phosphate-stimulated phosphorylation of Akt and endothelial nitric-oxide synthase (eNOS)Tatsuo Tanimoto
Center for Cardiovascular Research, University of Rochester, Rochester, New York 14642, USA
J Biol Chem 277:42997-3001. 2002b>Sphingosine 1-phosphate (S1P) and vascular endothelial growth factor (VEGF) elicit numerous biological responses including cell survival, growth, migration, and differentiation in endothelial cells mediated by the endothelial ..
- Sphingosine regulates the NLRP3-inflammasome and IL-1β release from macrophagesNadia M Luheshi
Faculty of Life Sciences, University of Manchester, Manchester, UK
Eur J Immunol 42:716-25. 2012..Here, we show that the endogenous lipid metabolite sphingosine (Sph) acts as a DAMP by inducing the NLRP3-inflammasome-dependent secretion of IL-1β from macrophages...
- Sphingosine-1-phosphate enhances satellite cell activation in dystrophic muscles through a S1PR2/STAT3 signaling pathwayKenneth C Loh
Children s Hospital Oakland Research Institute, Oakland, California, United States of America
PLoS ONE 7:e37218. 2012b>Sphingosine-1-phosphate (S1P) activates a widely expressed family of G protein-coupled receptors, serves as a muscle trophic factor and activates muscle stem cells called satellite cells (SCs) through unknown mechanisms...
- Immunosuppressive and anti-angiogenic sphingosine 1-phosphate receptor-1 agonists induce ubiquitinylation and proteasomal degradation of the receptorMyat Lin Oo
Center for Vascular Biology, University of Connecticut Health Center, Farmington, Connecticut 06030 3501, USA
J Biol Chem 282:9082-9. 2007b>Sphingosine 1-phosphate (S1P), a multifunctional lipid mediator, regulates lymphocyte trafficking, vascular permeability, and angiogenesis by activation of the S1P1 receptor...
- Vascular endothelial cell adherens junction assembly and morphogenesis induced by sphingosine-1-phosphateM J Lee
Center for Vascular Biology, Department of Physiology, University of Connecticut Health Center, Farmington 06030 3501, USA
Cell 99:301-12. 1999..We show here that sphingosine-1-phosphate (SPP), a platelet-derived bioactive lipid, activates the EDG-1 and -3 subtypes of G protein-coupled ..
- Modulation of cellular S1P levels with a novel, potent and specific inhibitor of sphingosine kinase-1Mark E Schnute
Pfizer Global Research and Development, St Louis Laboratories, Chesterfield, MO 63017, USA
Biochem J 444:79-88. 2012SphK (sphingosine kinase) is the major source of the bioactive lipid and GPCR (G-protein-coupled receptor) agonist S1P (sphingosine 1-phosphate)...
- Microarray analysis of altered sphingolipid metabolism reveals prognostic significance of sphingosine kinase 1 in breast cancerEugen Ruckhäberle
Department of Gynecology, J W Goethe University, 60590, Frankfurt, Germany
Breast Cancer Res Treat 112:41-52. 2008..The "sphingolipid rheostat" balances between apoptosis inducing ceramid and growth promoting sphingosine-1-phosphate...
- The sphingosine-1-phosphate transporter Spns2 expressed on endothelial cells regulates lymphocyte trafficking in miceShigetomo Fukuhara
Department of Cell Biology, National Cerebral and Cardiovascular Center Research Institute, Osaka, Japan
J Clin Invest 122:1416-26. 2012The bioactive lysophospholipid mediator sphingosine-1-phosphate (S1P) promotes the egress of newly formed T cells from the thymus and the release of immature B cells from the bone marrow...
- Suppression of cytokine storm with a sphingosine analog provides protection against pathogenic influenza virusKevin B Walsh
Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA
Proc Natl Acad Sci U S A 108:12018-23. 2011..With cytokine storm playing a role in the pathogenesis of a wide assortment of viral, bacterial, and immunologic diseases, a therapeutic approach using sphingosine analogs is of particular interest.
- Fingolimod, a sphingosine-1 phosphate receptor modulator, increases BDNF levels and improves symptoms of a mouse model of Rett syndromeRubén Deogracias
Biozentrum, University of Basel, 4056 Basel, Switzerland
Proc Natl Acad Sci U S A 109:14230-5. 2012..With this objective in mind, we used the sphingosine-1 phosphate receptor agonist fingolimod, a drug that crosses the blood-brain barrier...
- Release of sphingosine-1-phosphate from human platelets is dependent on thromboxane formationT Ulrych
Institut fur Pharmakologie und Klinische Pharmakologie, Universitatsklinikum Dusseldorf, Dusseldorf, Germany
J Thromb Haemost 9:790-8. 2011Platelets release the immune-modulating lipid sphingosine-1-phosphate (S1P). However, the mechanisms of platelet S1P secretion are not fully understood.
- HDL and its sphingosine-1-phosphate content in cardioprotectionPetra Keul
Institut fur Pathophysiologie, Zentrum fur Innere Medizin, Universitatsklinikum Essen, Hufelandstrasse 55, 45122 Essen, Germany
Heart Fail Rev 12:301-6. 2007..Studies on the involved mechanisms have revealed that the biologically active HDL-compound sphingosine-1-phosphate (S1P) is responsible for the beneficial effect of HDL on the myocardium...
- The role of sphingosine-1-phosphate transporter Spns2 in immune system functionAnastasia Nijnik
Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, United Kingdom
J Immunol 189:102-11. 2012b>Sphingosine-1-phosphate (S1P) is lipid messenger involved in the regulation of embryonic development, immune system functions, and many other physiological processes...
- Sphingosine kinase type 2 inhibition elevates circulating sphingosine 1-phosphateYugesh Kharel
Department of Pharmacology, University of Virginia, Charlottesville, VA 22908, USA
Biochem J 447:149-57. 2012S1P (sphingosine 1-phosphate) is a pleiotropic lipid mediator involved in numerous cellular and physiological functions. Of note among these are cell survival and migration, as well as lymphocyte trafficking...
- Sphingosine 1-phosphate as a major bioactive lysophospholipid that is released from platelets and interacts with endothelial cellsY Yatomi
Department of Laboratory Medicine, Yamanashi Medical University, Nakakoma, Japan
Blood 96:3431-8. 2000The serum-borne lysophospholipid mediators sphingosine 1-phosphate (Sph-1-P) and lysophosphatidic acid (LPA) have been shown to be released from activated platelets and to act on endothelial cells...
- Essential role for sphingosine kinases in neural and vascular developmentKiyomi Mizugishi
Genetics of Development and Disease Branch, NIDDK, National Institutes of Health, Bethesda, MD 20892 1821, USA
Mol Cell Biol 25:11113-21. 2005b>Sphingosine-1-phosphate (S1P), an important sphingolipid metabolite, regulates diverse cellular processes, including cell survival, growth, and differentiation...
- Sphingolipidomics: high-throughput, structure-specific, and quantitative analysis of sphingolipids by liquid chromatography tandem mass spectrometryAlfred H Merrill
School of Biology, Georgia Institute of Technology, Atlanta, GA 30332 0230, USA
Methods 36:207-24. 2005..closely related structurally and metabolically (for example, complex sphingolipids<-->ceramide<-->sphingosine<-->sphingosine 1-phosphate), to understand the role(s) of sphingolipids in a given context one must ..
- Sphingosine 1-phosphate levels in plasma and HDL are altered in coronary artery diseaseKatherine J E Sattler
Institute for Pathophysiology, University Duisburg Essen, Hufelandstr 55, 45122, Essen, Germany
Basic Res Cardiol 105:821-32. 2010High-density lipoproteins (HDL) are the major plasma carriers for sphingosine 1-phosphate (S1P) in healthy individuals, but their S1P content is unknown for patients with coronary artery disease (CAD)...
- FTY720 shows promising in vitro and in vivo preclinical activity by downmodulating Cyclin D1 and phospho-Akt in mantle cell lymphomaQing Liu
Division of Pharmaceutics, College of Pharmacy, The Ohio State University, Columbus, Ohio 43210, USA
Clin Cancer Res 16:3182-92. 2010..Because of the absence of curative therapy for MCL, we explored FTY720 as a novel agent against MCL...
- FTY720 (fingolimod) sensitizes prostate cancer cells to radiotherapy by inhibition of sphingosine kinase-1Dmitri Pchejetski
Department of Surgery and Cancer, Imperial College London, London, United Kingdom
Cancer Res 70:8651-61. 2010..Dose escalation improves local response rates but is limited by tolerance in normal tissues. A sphingosine analogue, FTY720 (fingolimod), a drug currently in phase III studies for treatment of multiple sclerosis, has ..
- Brain sphingosine-1-phosphate receptors: implication for FTY720 in the treatment of multiple sclerosisKumlesh K Dev
Department of Anatomy and Neuroscience, University College Cork, Windle Building, Cork, Ireland
Pharmacol Ther 117:77-93. 2008..This drug attenuates trafficking of harmful T cells entering the brain by regulating sphingosine-1-phosphate (S1P) receptors...
- BACE1 activity is modulated by cell-associated sphingosine-1-phosphateNobumasa Takasugi
Department of Neuropathology and Neuroscience, Graduate School of Medicine, The University of Tokyo, Bunkyo ku, Tokyo 113 0033, Japan
J Neurosci 31:6850-7. 2011b>Sphingosine kinase (SphK) 1 and 2 phosphorylate sphingosine to generate sphingosine-1-phosphate (S1P), a pluripotent lipophilic mediator implicated in a variety of cellular events...
- Essential requirement for PP2A inhibition by the oncogenic receptor c-KIT suggests PP2A reactivation as a strategy to treat c-KIT+ cancersKathryn G Roberts
School of Biomedical Sciences, University of Newcastle, Callaghan, New South Wales, Australia
Cancer Res 70:5438-47. 2010..Our findings show that PP2A inhibition is essential for c-KIT-mediated tumorigenesis, and that reactivating PP2A may offer an attractive strategy to treat drug-resistant c-KIT(+) cancers...
- Circulating sphingolipid biomarkers in models of type 1 diabetesTodd E Fox
Department of Pharmacology, Penn State College of Medicine, Milton S Hershey Medical Center, Hershey, PA, USA
J Lipid Res 52:509-17. 2011..The results reveal that sphingosine-1-phosphate (So1P) is elevated in both diabetic models in comparison to respective control animals...
- The sphingosine-1-phosphate analogue FTY720 reduces atherosclerosis in apolipoprotein E-deficient micePetra Keul
Institute of Pathophysiology, University Hospital Essen, Hufelandstrasse 55, 45122 Essen, Germany
Arterioscler Thromb Vasc Biol 27:607-13. 2007The sphingosine-1-phosphate (S1P) analogue FTY720 is a potent immunosuppressive agent currently in Phase III clinical trials for kidney transplantation...
- Transactivation of sphingosine-1-phosphate receptors by FcepsilonRI triggering is required for normal mast cell degranulation and chemotaxisPuneet S Jolly
Department of Biochemistry, Virginia Commonwealth University Medical Center, Richmond 23298, USA
J Exp Med 199:959-70. 2004..of the high-affinity receptor for IgE (FcepsilonRI) in RBL-2H3 and bone marrow-derived mast cells activates sphingosine kinase (SphK), which leads to generation and secretion of the potent sphingolipid mediator, sphingosine-1-..
- Sphingosine kinase, sphingosine-1-phosphate, and apoptosisMichael Maceyka
Department of Biochemistry, Medical College of Virginia Campus, Virginia Commonwealth University, 1101 E Marshall St, Richmond, VA 23298 0614, USA
Biochim Biophys Acta 1585:193-201. 2002The sphingolipid metabolites ceramide (Cer), sphingosine (Sph), and sphingosine-1-phosphate (S1P) play an important role in the regulation of cell proliferation, survival, and cell death...
- A critical role for the sphingosine analog AAL-R in dampening the cytokine response during influenza virus infectionDavid Marsolais
Department of Chemical Physiology and Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA
Proc Natl Acad Sci U S A 106:1560-5. 2009..Here we report that immune modulation by local administration to the respiratory tract of sphingosine analog AAL-R significantly dampens the release of cytokines and chemokines while maintaining protective ..
- Vascular endothelium as a contributor of plasma sphingosine 1-phosphateKrishnan Venkataraman
Center for Vascular Biology, Department of Cell Biology, University of Connecticut Health Center, Farmington, CT 06030, USA
Circ Res 102:669-76. 2008b>Sphingosine 1-phosphate (S1P), an abundant lipid mediator in plasma, regulates vascular and immune cells by activating S1P receptors. In this report, we investigated the mechanisms by which high plasma S1P levels are maintained in mice...
- Fingolimod (FTY720) enhances remyelination following demyelination of organotypic cerebellar slicesVeronique E Miron
Neuroimmunology Unit, McGill University, Montreal Neurological Institute, 3801 University St, Montreal, QC, Canada, H3A 2B4
Am J Pathol 176:2682-94. 2010....
- Th17 central memory T cells are reduced by FTY720 in patients with multiple sclerosisM Mehling
Department of Neurology, University Hospitals Basel, Petersgraben 4, CH 4031 Basel, Switzerland
Neurology 75:403-10. 2010FTY720 is a sphingosine 1-phosphate (S1P) receptor modulator that showed efficacy in phase II and III clinical trials in patients with multiple sclerosis (MS)...
- CD69 suppresses sphingosine 1-phosophate receptor-1 (S1P1) function through interaction with membrane helix 4Alexander J Bankovich
Howard Hughes Medical Institute and Department of Microbiology and Immunology, University of California, San Francisco, California 94143, USA
J Biol Chem 285:22328-37. 2010Lymphocyte egress from lymph nodes requires the G-protein-coupled sphingosine 1-phosphate receptor-1 (S1P(1)). The activation antigen CD69 associates with and inhibits the function of S1P(1), inhibiting egress...
- The S1P(1)-mTOR axis directs the reciprocal differentiation of T(H)1 and T(reg) cellsGuangwei Liu
Department of Immunology, St Jude Children s Research Hospital, Memphis, Tennessee, USA
Nat Immunol 11:1047-56. 2010..regulatory T cells (T(reg) cells) was reciprocally regulated by S1P(1), a receptor for the bioactive lipid sphingosine 1-phosphate (S1P)...
- Brain penetration of the oral immunomodulatory drug FTY720 and its phosphorylation in the central nervous system during experimental autoimmune encephalomyelitis: consequences for mode of action in multiple sclerosisCarolyn A Foster
Novartis Institutes for BioMedical Research, Vienna, Austria
J Pharmacol Exp Ther 323:469-75. 2007FTY720 [2-amino-2-[2-(4-octylphenyl) ethyl]propane-1,3-diol hydrochloride] is an oral sphingosine-1-phosphate receptor modulator under development for the treatment of multiple sclerosis (MS)...
- Novel insight into stem cell mobilization-plasma sphingosine-1-phosphate is a major chemoattractant that directs the egress of hematopoietic stem progenitor cells from the bone marrow and its level in peripheral blood increases during mobilization due to M Z Ratajczak
Stem Cell Biology Program at the James Graham Brown Cancer Center, University of Louisville, Louisville, KY 40202, USA
Leukemia 24:976-85. 2010..chemotactic activity after charcoal stripping suggested the involvement of bioactive lipids and we focused on sphingosine-1-phosphate (S1P), a known chemoattracant of HSPCs...
- Characterization of ceramide synthase 2: tissue distribution, substrate specificity, and inhibition by sphingosine 1-phosphateElad L Laviad
Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel
J Biol Chem 283:5677-84. 2008..Interestingly, the activity of CerS2 can be regulated by another bioactive sphingolipid, sphingosine 1-phosphate (S1P), via interaction of S1P with two residues that are part of an S1P receptor-like motif found ..
- High-density lipoproteins and their constituent, sphingosine-1-phosphate, directly protect the heart against ischemia/reperfusion injury in vivo via the S1P3 lysophospholipid receptorGregor Theilmeier
Institute for Anatomy, Department of Anesthesiology and Intensive Care, University Hospital Munster, Vesaliusweg 2 4, 48149 Munster, Germany
Circulation 114:1403-9. 2006..We hypothesized that some of the cholesterol transport-independent biological properties of high-density lipoprotein (HDL) implied in atheroprotection may also be beneficial in settings of acute myocardial reperfusion injury...
- Metabolism and biological functions of two phosphorylated sphingolipids, sphingosine 1-phosphate and ceramide 1-phosphateAkio Kihara
Laboratory of Biomembrane and Biofunctional Chemistry, Faculty of Pharmaceutical Sciences, Hokkaido University, Nishi 6 choume, Sapporo, Japan
Prog Lipid Res 46:126-44. 2007..Recent studies have revealed that some sphingolipid metabolites, such as long-chain bases (LCBs; sphingosine (Sph) in mammals), long-chain base 1-phosphates (LCBPs; sphingosine 1-phosphate (S1P) in mammals), ceramide (..
- Isoflurane posttreatment reduces neonatal hypoxic-ischemic brain injury in rats by the sphingosine-1-phosphate/phosphatidylinositol-3-kinase/Akt pathwayYilin Zhou
Department of Anesthesiology, Loma Linda University School of Medicine, Loma Linda, Calif 92354, USA
Stroke 41:1521-7. 2010..posttreatment provides neuroprotection after neonatal hypoxia-ischemia (HI) in rats and evaluated the role of the sphingosine-1-phosphate/phosphatidylinositol-3-kinase/Akt pathway in this volatile anesthetic-mediated neuroprotection.
- Myocardial dysfunction with coronary microembolization: signal transduction through a sequence of nitric oxide, tumor necrosis factor-alpha, and sphingosineMatthias Thielmann
Abteilung für Pathophysiologie, Zentrum fur Innere Medizin, Universitatsklinikum Essen, Germany
Circ Res 90:807-13. 2002..TNF-alpha uses a signal transduction involving nitric oxide (NO) and/or sphingosine. Therefore, we induced coronary microembolization in anesthetized dogs and studied the role and sequence of NO, ..
- Effect of high fat diet enriched with unsaturated and diet rich in saturated fatty acids on sphingolipid metabolism in rat skeletal muscleAgnieszka Blachnio-Zabielska
Department of Physiology, Medical University of Bialystok, Bialystok, Poland
J Cell Physiol 225:786-91. 2010..The content of ceramide, sphinganine, sphingosine, and sphingosine-1-phosphate was also measured...
- Sphingosine 1-phosphate regulates the egress of IgA plasmablasts from Peyer's patches for intestinal IgA responsesMasashi Gohda
Division of Mucosal Immunology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Minato ku, Tokyo 108 8639, Japan
J Immunol 180:5335-43. 2008..In this study, we show that alterations in type 1 sphingosine 1-phosphate (S1P) receptor expression during B cell differentiation in the PPs control the emigration of IgA ..
- Plasma lipoproteins behave as carriers of extracellular sphingosine 1-phosphate: is this an atherogenic mediator or an anti-atherogenic mediator?Fumikazu Okajima
Laboratory of Signal Transduction, Institute for Molecular and Cellular Regulation, Gunma University, 3 39 15 Showa Machi, Maebashi, Japan
Biochim Biophys Acta 1582:132-7. 2002b>Sphingosine 1-phosphate (S1P) concentration in plasma and serum has been estimated to be within 200-900 nM...
- Sphingosine kinase-1 and sphingosine 1-phosphate receptor 2 mediate Bcr-Abl1 stability and drug resistance by modulation of protein phosphatase 2AArelis Salas
Department of Biochemistry and Molecular Biology, Hollings Cancer Center, Medical University of South Carolina, Charleston, SC, USA
Blood 117:5941-52. 2011The mechanisms by which sphingosine kinase-1 (SK-1)/sphingosine 1-phosphate (S1P) activation contributes to imatinib resistance in chronic myeloid leukemia (CML) are unknown...
- Sphingosine-1-phosphate lyase deficiency produces a pro-inflammatory response while impairing neutrophil traffickingMaria L Allende
Genetics of Development and Disease Branch, NIDDK, National Institutes of Health, Bethesda, Maryland 20892, USA
J Biol Chem 286:7348-58. 2011b>Sphingosine-1-phosphate (S1P) lyase catalyzes the degradation of S1P, a potent signaling lysosphingolipid. Mice with an inactive S1P lyase gene are impaired in the capacity to degrade S1P, resulting in highly elevated S1P levels...
- Sphingosine 1-phosphate reduces vascular leak in murine and canine models of acute lung injuryBryan J McVerry
Division of Pulmonary and Critical Care Medicine, Center for Translational Respiratory Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA
Am J Respir Crit Care Med 170:987-93. 2004..To extend our in vitro observations concerning the barrier-protective effects of the lipid growth factor sphingosine 1-phosphate (Sph 1-P), we assessed the ability of Sph 1-P to prevent regional pulmonary edema accumulation in ..
- Sphingosine-1-phosphate: A bioactive lipid that confers high-density lipoprotein with vasculoprotection mediated by nitric oxide and prostacyclinCristina Rodriguez
Centro de Investigacion Cardiovascular CSIC ICCC, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
Thromb Haemost 101:665-73. 2009b>Sphingosine-1-phosphate (S1P) is a bioactive lipid generated in the intracellular membranes from the metabolism of sphingomyelin...
- Sphingosine facilitates SNARE complex assembly and activates synaptic vesicle exocytosisFrédéric Darios
MRC Laboratory of Molecular Biology, Cambridge CB2 0QH, UK
Neuron 62:683-94. 2009..We show that sphingosine, a releasable backbone of sphingolipids, activates synaptobrevin in synaptic vesicles to form the SNARE complex ..
- Sphingosine 1-phosphate lyase deficiency disrupts lipid homeostasis in liverMeryem Bektas
Genetics of Development and Disease Branch, NHLBI, National Institutes of Health, Bethesda, Maryland 20892, USA
J Biol Chem 285:10880-9. 2010The cleavage of sphingoid base phosphates by sphingosine-1-phosphate (S1P) lyase to produce phosphoethanolamine and a fatty aldehyde is the final degradative step in the sphingolipid metabolic pathway...
- Antitumor activity of sphingosine kinase 2 inhibitor ABC294640 and sorafenib in hepatocellular carcinoma xenograftsVladimir Beljanski
Drug Discovery Core Hollings Cancer Center, Medical University of South Carolina, Charleston, USA
Cancer Biol Ther 11:524-34. 2011The balance between the pro-apoptotic lipids ceramide and sphingosine and the pro-survival lipid sphingosine 1-phosphate (S1P) is termed the "sphingosine rheostat"...
- Role for sphingosine kinase 1 in colon carcinogenesisToshihiko Kawamori
Department of Pathology and Laboratory Medicine, Medical University of South Carolina, 165 Ashley Ave, Ste 309, Charleston, SC 29425, USA
FASEB J 23:405-14. 2009b>Sphingosine kinase 1 (SphK1) phosphorylates sphingosine to form sphingosine-1-phosphate (S1P) and is a critical regulator of sphingolipid-mediated functions. Cell-based studies suggest a tumor-promoting function for the SphK1/S1P pathway...
- Natural killer cell trafficking in vivo requires a dedicated sphingosine 1-phosphate receptorThierry Walzer
Centre d immunologie de Marseille Luminy, Universite de la Mediterranee, Institut National de la Sante et de la Recherche Medicale, U631, and Centre National de la Recherche Scientifique, UMR6102, Marseille, France
Nat Immunol 8:1337-44. 2007..The lysophospholipid sphingosine 1-phosphate (S1P), by binding to its receptor S1P1, regulates the recirculation of T and B lymphocytes...
- Extracellular and intracellular actions of sphingosine-1-phosphateGRAHAM M STRUB
Department of Biochemistry and Molecular Biology, VCU School of Medicine, 1101 E Marshall Street, 2 011 Sanger Hall, Richmond, Virginia 23298, USA
Adv Exp Med Biol 688:141-55. 2010b>Sphingosine-1-phosphate (S1P) is a bioactive lipid mediator with crucial roles in a wide variety of cellular functions across a broad range of organisms. Though a simple molecule in structure, S1P functions are complex...
- FTY720, a synthetic sphingosine 1 phosphate analogue, inhibits development of atherosclerosis in low-density lipoprotein receptor-deficient miceJerzy Roch Nofer
Institut fur Klinische Chemie und Laboratoriumsmedizin, Westfalische Wilhelms Universitat Munster, Albert Schweizer Str 33, D 48129 Munster, Germany
Circulation 115:501-8. 2007Numerous in vitro studies suggest that sphingosine 1-phosphate (S1P), a bioactive lysosphingolipid associated with high-density lipoproteins, accounts at least partly for the potent antiinflammatory properties of high-density lipoprotein ..
- Sphingosine 1-phosphate, a bioactive sphingolipid abundantly stored in platelets, is a normal constituent of human plasma and serumY Yatomi
Department of Laboratory Medicine, Yamanashi Medical University, Nakakoma gun
J Biochem 121:969-73. 1997Although sphingosine 1-phosphate (Sph-1-P) is reportedly involved in diverse cellular processes and the physiological roles of this bioactive sphingolipid have been strongly suggested, few studies have revealed the presence of Sph-1-P in ..
- FTY720 produces caspase-independent cell death of acute lymphoblastic leukemia cellsCraig T Wallington-Beddoe
Westmead Institute for Cancer Research, Westmead Millennium Institute, The University of Sydney, Sydney, Australia
Autophagy 7:707-15. 2011..FTY720 is an active drug in vitro in ALL cell lines and patient samples. Evidence supports a caspase-independent mechanism of cell death with the occurrence of autophagy and necrosis...
- Sphingolipids and cancer: ceramide and sphingosine-1-phosphate in the regulation of cell death and drug resistanceSuriyan Ponnusamy
Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC, USA
Future Oncol 6:1603-24. 2010..In addition, ceramide metabolism to generate sphingosine-1-phosphate (S1P) by sphingosine kinases 1 and 2 mediates, with or without the involvement of G-protein-coupled ..
- Regulation and functional roles of sphingosine kinasesRegina Alemany
Institut fur Pharmakologie, Universitat Duisburg Essen, Hufelandstrasse 55, 45122 Essen, Germany
Naunyn Schmiedebergs Arch Pharmacol 374:413-28. 2007b>Sphingosine kinases (SphKs) catalyze the phosphorylation of sphingosine to sphingosine-1-phosphate (S1P)...
- The immunomodulatory sphingosine 1-phosphate analog FTY720 reduces lesion size and improves neurological outcome in a mouse model of cerebral ischemiaBozena Czech
Pharmazentrum Frankfurt, Klinikum der Johann Wolfgang Goethe Universitat, Theodor Stern Kai 7, 60590 Frankfurt am Main, Germany
Biochem Biophys Res Commun 389:251-6. 2009..The lipid signaling mediator sphingosine 1-phosphate-derived stable analog FTY720 (fingolimod) acts as an immunosuppressant and induces lymphopenia by ..
- FTY720 (fingolimod) in Multiple Sclerosis: therapeutic effects in the immune and the central nervous systemVolker Brinkmann
Autoimmunity, Transplantation and Inflammation, Novartis Institutes for BioMedical Research, Basel, Switzerland
Br J Pharmacol 158:1173-82. 2009FTY720 (fingolimod) is a first-in-class sphingosine 1-phosphate (S1P) receptor modulator that was highly effective in Phase II clinical trials for Multiple Sclerosis (MS)...
- Erythrocytes serve as a reservoir for cellular and extracellular sphingosine 1-phosphateConstantin Bode
Institute for Immunology, Hannover Medical School, Carl Neuberg Str 1, 30625 Hanover, Germany
J Cell Biochem 109:1232-43. 2010b>Sphingosine 1-phosphate (S1P) in blood is phosphorylated, stored, and transported by red blood cells (RBC). Release of S1P from RBC into plasma is a regulated process that does not occur in plasma- or serum-free media...
- An update on sphingosine-1-phosphate and other sphingolipid mediatorsHenrik Fyrst
Center for Cancer Research, Children s Hospital Oakland Research Institute, Oakland, California, USA
Nat Chem Biol 6:489-97. 2010..Membrane sphingolipids also serve as a reservoir for bioactive metabolites including sphingosine, ceramide, sphingosine-1-phosphate and ceramide-1-phosphate...
- Sphingosine-1-phosphate: the Swiss army knife of sphingolipid signalingMichael Maceyka
Department of Biochemistry and Molecular Biology, Virginia Commonwealth University School of Medicine, Richmond, VA 23298, USA
J Lipid Res 50:S272-6. 2009The sphingolipid metabolite sphingosine-1-phosphate (S1P) and the kinases that produce it have emerged as critical regulators of numerous fundamental biological processes important for health and disease...
- Sphingosine-1-phosphate and sphingosine kinase are critical for transforming growth factor-beta-stimulated collagen production by cardiac fibroblastsNicole Gellings Lowe
Department of Biology, San Diego State University, 5500 Campanile Dr, San Diego, CA 92182 4614, USA
Cardiovasc Res 82:303-12. 2009..Excess production of ECM associated with cardiac fibrosis severely inhibits cardiac function. Sphingosine-1-phosphate (S1P), a bioactive lysophospholipid, regulates the function of numerous cell types...
- FASEB SRC on Lysophospholipd Mediators in Health and DiseaseJulie D Saba; Fiscal Year: 2011..The lysophospholipids sphingosine- 1-phosphate (S1P) and lysophosphatidic acid (LPA) are bioactive lipids generated via catabolism of membrane ..
- Sphingolipid Metabolism in Drosophila DevelopmentJulie D Saba; Fiscal Year: 2013..Further, we have shown that Sply mutants lacking expression of Drosophila sphingosine-1-phosphate (S1P) lyase (SPL), which is responsible for the final step of sphingolipid degradation, accumulate ..
- Cellular &Inflammatory Pathways in Ashtma &Allergic Diseases: From IgE to CellsLAWRENCE BARRY SCHWARTZ; Fiscal Year: 2012..Project 3 on studies of Lyn kinase involvement in desensitization, and with Project 4 on the involvement of sphingosine kinase-1 in desensitization of human mast cells and basophils facilitate these mechanistic studies. 3...
- Ceramide Metabolism and Photoreceptor HomeostasisUsha R Acharya; Fiscal Year: 2013..applicant): Sphingolipids are essential components of all eukaryotic cell membranes;many of them like ceramide, sphingosine 1-phosphate are also bioactive lipids regulating cellular functions ranging from apoptosis to angiogenesis...
- Regulation of Hepatic SphK2 by Bile Acids: Effects on Lipid MetabolismHUIPING ROSE ZHOU; Fiscal Year: 2013..Our most recent studies show that bile acids upregulate sphingosine kinase 2 (SphK2) expression (at both mRNA and protein levels) and enzyme activity and increase serum ..
- Treatment of Inflammatory Bowel Disease with Ceramidase InhibitorsLynn W Maines; Fiscal Year: 2012..Accumulating evidence demonstrates that sphingosine-1-phosphate (S1P) produced by the combined action of sphingomyelinases, neutral ceramidase and sphingosine ..
- Sphingosine 1-phosphate receptors in vascular homeostasis and pathologyTIMOTHY TUN HLA; Fiscal Year: 2012b>Sphingosine 1-phosphate (S1P), a multifunctional lipid mediator, signals via the S1P receptors (S1PnR) to regulate the development, homeostasis and phenotypic changes of the vascular system...
- Sphingosine 1-phosphate and cardioprotectionJOEL SAMUEL KARLINER; Fiscal Year: 2012This proposal is based on our prior studies documenting the fundamental importance of sphingosine kinase/sphingosine 1-phosphate (S1P) in myocardial resistance to injury...
- Novel Functions of S1P in NeuroinflammationTOMASZ K KORDULA; Fiscal Year: 2013..We have shown that IL-1 stimulates and upregulates sphingosine kinase 1 (SphK1), one of the two isoenzymes that generate sphingosine-1-phosphate (S1P), a lipid mediator that ..
- Nuclear Lipids in SteroidogenesisMarion B Sewer; Fiscal Year: 2013..ASAH1b is one of three ceramidases that produces sphingosine (SPH)...
- SEX EFFECTS ON CHEMOKINE MEDIATED CNS AUTOIMMUNITYLillian Cruz-Orengo; Fiscal Year: 2012..from naove 10 week-old male and female SJL mice detected significantly 2-fold increased expression of the Sphingosine 1-Phosphate Receptor 2 (S1PR2), also known as Edg-5, in the cerebella of female SJL mice compared with male SJL ..
- Sphingolipids in Acute Kidney InjuryMARK DOUGLAS OKUSA; Fiscal Year: 2013..One strategy that has evolved over the last few years involves sphingosine 1-phosphate receptor (S1PR) agonists...
- Novel functions of RGS3Nickolai O Dulin; Fiscal Year: 2012..of Gq- and Gi-coupled receptors to angiotensin II, endothelin-1, carbachol, gonadotropin-releasing hormone and sphingosine-1 phosphate...
- Sphingosine 1-Phosphate: A New Target for Early Diabetic RetinopathyArup Das; Fiscal Year: 2013..Our long-term goal is o fully characterize a novel pathway, sphingosine 1 phosphate (S1P) in diabetic retinopathy, and identify novel targets for the treatment of this blinding ..
- Generation of Wunen/LPP3-based therapy for muscular dystrophyHannele Ruohola Baker; Fiscal Year: 2010..LPP3) which many studies have shown is involved in the regulation of levels of bioactive lipids, particularly sphingosine 1-phosphate (S1P)...
- Sphingosine 1 phosphate receptors 1 and 3 as novel targets in transplantationAmandeep Bajwa; Fiscal Year: 2013..My work as a postdoctoral fellow has recently revealed a novel role of kidney proximal tubule sphingosine-1-phosphate-receptor-1 (S1P1) activation. Kidney proximal tubule S1P1 activation protects kidneys from IRI...
- Novel Therapies and Biomarkers for the MucopolysaccharidosesCALOGERA MARIA SIMONARO; Fiscal Year: 2013..examining the mechanisms leading to GAG-mediated abnormalities in two important signaling lipids, ceramide and sphingosine-1-phosphate (S1P)...
- Gender Effects on Remodeling of Lipid and Sarcomere Dynamics in HypertrophyE Douglas Lewandowski; Fiscal Year: 2013..consequential effects on myocardial 2-D strains, tissue stiffness and contractility and b) ceramide species and sphingosine production and consequential effects on myofilament phosphorylation, oxidation and Ca-responsiveness in hearts ..
- The S1P1 receptor regulates sarcomere assembly and cardiac developmentRoland S Wu; Fiscal Year: 2013..b>Sphingosine-1-phosphate (S1P) has been found to play an important role in vertebrate development...
- Protective Role of the S1P-S1P1 Pathway in Pulmonary FibrosisAndrew M Tager; Fiscal Year: 2013..We have recently demonstrated that the potent lipid mediator sphingosine 1-phosphate (S1P) protects against the development of pulmonary fibrosis in mice induced by bleomycin lung ..
- GLYCOSPHINGOLIPID METABOLISM AND MENTAL RETARDATIONGlyn Dawson; Fiscal Year: 2013..outcome of our two major specific aims, is to verify the hypothesis that microdomain regulation of ceramide, sphingosine and sphingosine-1-phosphate (S1P) is achieved by several different mechanisms, that S1P depletion is common to ..
- Sphingolipid Metabolism and Signaling in the RetinaMd Nawajes A Mandal; Fiscal Year: 2013..Ceramide (Cer) is the key metabolite for all sphingolipid biosynthesis. Cer and its metabolite sphingosine-1-phosphate (S1P) are signaling sphingolipids;implicated in several human diseases associated with inflammation,..
- Neuron-Dervied S1P and Endothelial Function in StrokeChristian Waeber; Fiscal Year: 2010..In brain EC, sphingosine-1-phosphate (S1P) induces Akt/endothelial nitric oxide synthase (eNOS) activation, suppresses apoptosis and ..
- Calcium-dependent Regulation of Smooth Muscle PhenotypeBRIAN WAMHOFF; Fiscal Year: 2010..Exciting recent studies from our lab provide evidence showing that the contractile agonist sphingosine-1-phosphate increases SMGX in part via VGCCs/Rho-kinase/SRF and selective S1P receptor subtypes...
- Roles of Sphingolipids in the Pathophysiology of Obesity and DiabetesLAUREN ASHLEY COWART; Fiscal Year: 2013..novel discovery that fatty acids (which are elevated in plasma in obese individuals) increase the expression of sphingosine kinase 1 in cultured skeletal muscle cells...
- Endothelial Injury in Endotoxin-Induced Acute Renal FailurePatrick N Cunningham; Fiscal Year: 2013..b>Sphingosine-1-phosphate analogues, which maintain endothelial barrier integrity, will also be administered to determine the ..
- Signaling Sphingolipids in COPDIrina Petrache; Fiscal Year: 2009..Signaling sphingolipids are essential for ensuring an optimal balance of cell death (ceramides) / survival (sphingosine-1-phosphate, S1P) in tissues...
- Interactions of Lipoproteins and Cells in Diabetes MellitusRICHARD LOUIS KLEIN; Fiscal Year: 2013..suggests that HDL may contribute additionally through its role as the primary transport lipoprotein for sphingosine-1-phosphate (S1P), a key, bioactive lipid which regulates a variety of beneficial cellular functions...
- Synthesis of Novel Bioactive Sphingolipids as a ResourceRobert Bittman; Fiscal Year: 2013The goal of this resource is to synthesize a wide range of variants of bioactive sphingosine 1-phosphate (81P) and glycosphingolipids that will be made available for collaborators with NHLBI and other investigators whose studies are ..
- Soy sphingadienes and related compounds in colon cancer chemoprevention and treatJulie D Saba; Fiscal Year: 2010..Finally, sphingadienes have the potential to inhibit sphingosine kinase, an oncoprotein that is overexpressed in colon cancer and required for intestinal tumor progression...
- Glial Interactions in Premyelinating Oligodendrocyte DestructionJianrong Li; Fiscal Year: 2012..altered ceramide metabolism in astrocytes potentiates preOL injury;and (3) to investigate whether modulating sphingosine-1-phosphate signaling pathway confers protection in a rat model of PVL...
- Antimicrobial Lipids within the Oral CavityPHILIP WESLEY WERTZ; Fiscal Year: 2010..2. To delineate antimicrobial activity of C16:1_6 and free long-chain bases (sphingosine, dihydrosphingosine, phytosphingosine and 6-hydroxysphingosine) against selected strains of the periodontal ..
- Sphingolipid Signaling in Endothelial Responses to InjuryTERESA SANCHEZ GARCIA-VAO; Fiscal Year: 2013b>Sphingosine-1-phosphate (S1P), a blood-borne sphingolipid, regulates many cellular functions (e.g. migration, survival) through the interaction with its G protein coupled receptors S1P1-5R...
- Improvement of Liver Transplantation by a Sphingosine Kinase InhibitorZhi Zhong; Fiscal Year: 2010..Our recent exciting observations indicate that inhibition of sphingosine kinase (SK) dramatically decreases PNF after hepatic warm IR in vivo, suggesting that sphingolipids may be key ..
- Opposing and complementary roles of KLF1 and KLF2 in erythropoiesisJoyce A Lloyd; Fiscal Year: 2012..We will determine the amounts of mRNA for KLF1 and KLF2 target genes, such as FoxM1, Myc, CD24a antigen, sphingosine kinase 1, Pura and parathyroid hormone 1 receptor, in KLF1+/-KLF2-/-, KLF1-/- KLF2+/-, KLF2-/-, KLF1-/- and ..
- S1P Lyase in colon cancerJulie D Saba; Fiscal Year: 2013DESCRIPTION (provided by applicant): Dietary sphingolipids such as sphingosine and ceramide promote enterocyte turnover and have been shown to protect against intestinal tumorigenesis in mice...
- Plasma Gelsolin and Host Defense After Lung InjuryLester Kobzik; Fiscal Year: 2013..g. sphingosine-1-phosphate to its receptor (S1PR1), through binding and competition assays, and use of S1P receptor knockout ..
- Regulation of GPER-mediated Signaling in the Vasculature by CalmodulinKim Tran; Fiscal Year: 2012..the platelet-endothelial cell adhesion molecule (PECAM-1), and the potential interaction between PECAM-1 and sphingosine 1 phosphate receptor 1 (S1P1)...
- Protective Role of Intracellular S1P in Lung InjuryViswanathan Natarajan; Fiscal Year: 2010..Our in vivo and in vitro studies indicate that sphingosine-1-phosphate (S1P), a naturally occurring bioactive lipid, is an essential angiogenic factor that regulates ..
- Intracellular Target of Sphingosine-1-PhosphateGRAHAM M STRUB; Fiscal Year: 2010DESCRIPTION (provided by applicant): Sphingosine-1-phosphate (S1P) is a potent bioactive lipid that plays key roles in brain development, neuronal survival, and nervous system remodeling...
- Regulation and Role of Ceramidase in InflammationLina M Obeid; Fiscal Year: 2013..Ceramidases breakdown ceramide to generate sphingosine and sphingosine-1-phosphate (S1P) which in turn mediates several biologic activities, including inflammatory ..
- REGULATION OF BRAIN THROMBOSIS IN STROKE MODELSBerislav V Zlokovic; Fiscal Year: 2013..human BEC and neurogenesis from human neuronal progenitor cells (NPC) in processes that require EPCR, PAR1 and sphingosine 1-phosphate receptor 1 (S1P1), and PAR1, PAR3 and S1P1, respectively...
- Characterization of a GPCR-blocking antibody for the treatment of breast cancer.GARRET GUENTHER; Fiscal Year: 2011..A compound known as sphingosine 1-phosphate (S1P) may be a major determinant of the aggressiveness and drug resistance of breast cancer...
- Guanylyl cyclase receptors: Targets for medical interventionJoseph P Albanesi; Fiscal Year: 2010..We recently identified sphingosine-1 -phosphate (S1P) as a potent, effective and highly specific GCB desensitization factor...
- Barrier Dysfunction in Severe Surgical DiseasesDouglas J Turner; Fiscal Year: 2012..The bioactive sphingolipid sphingosine-1-phosphate (S1P) has recently demonstrated significant effects on endothelial cells in promoting important ..
- Ethanol-induced Lower Jaw Loss in Bmp Signaling Pathway MutantsCHARLES BENJAMIN LOVELY; Fiscal Year: 2013..Mutation of the sphingosine receptor, s1pr2, causes strikingly similar defects to Meckel's cartilage due to disrupted morphogenesis of ..
- Improving Primordial Follicle Survival After Transplantation of Cryopreserved HumKutluk H Oktay; Fiscal Year: 2012..To determine whether a ceramide-induced cell death pathway inhibitor, sphingosine-1 phosphate (S1P), protects against post-transplant ischemia-induced damage to ovarian primordial follicle pool ..
- HIV-induced immune activation impairs immune reconstitution through S1PChristel H Uittenbogaart; Fiscal Year: 2013..From studies in the mouse it has become apparent that Sphingosine-1-phosphate (S1P) and one of its receptors, S1P receptor-1 (S1P-R1) play essential roles in egress of naive T ..
- Exploring the roles of Gi and S1Pr1 in endothelial barrier function in vivoLISA DIANE WILSBACHER; Fiscal Year: 2013..research proposal aims to uncover signaling mechanisms that regulate vascular integrity, particularly through sphingosine-1-phosphate receptor 1 (S1Pr1) and Gi signaling...
- Production &Crystallization of Membrane Protein for 3D StructureLawrence J Delucas; Fiscal Year: 2013..ENaC and cystic fibrosis transmembrane regulator protein, CFTR), two GPCRs (chemokine receptor-1, CCR1 and sphingosine- 1 phosphate receptor, S1P) and growth hormone receptor, GHR...
- The Sphingolipid Pathway in Colon Cancer ChemopreventionToshihiko Kawamori; Fiscal Year: 2013..Sphingolipid metabolites such as ceramide, sphingosine, and sphingosine 1-phosphate (S1P) are a new class of lipid messengers that regulate cell proliferation, ..
- Vascular Sphingosine Kinase Signaling in Cerebral Ischemic ToleranceBRADLEY KENT WACKER; Fiscal Year: 2010..intend to facilitate the search for therapeutic targets for stroke by elucidating the role of cerebrovascular sphingosine kinase (SphK) signaling in the mechanism by which hypoxic preconditioning (HPC) affords ischemic protection to ..
- Regulation of Lymphocyte Trafficking by S1P1 and CD69Mehrdad Matloubian; Fiscal Year: 2012..We have found that expression of a phospholipid receptor, sphingosine-1-phosphate receptor-1 (S1P1), within lymphocytes is required for their ability to exit from secondary lymphoid ..
- Sphingolipids in Cell Death after PhotodamageDUSKA M SEPAROVIC; Fiscal Year: 2012..The balance between the proapoptotic (pro-death) sphingolipid (SL) ceramide and the antiapoptotic SL sphingosine-1- phosphate (S1P) constitutes the SL rheostat...
- Pseudomonas detection and metabolism of sphingosineMatthew J Wargo; Fiscal Year: 2013..Preliminary data demonstrate that P. aeruginosa can degrade the potent immune signaling molecule sphingosine-1-phosphate (S1P) and its precursor sphingosine. S1P degradation would allow P...
- Regulation of Smooth Muscle Differentiation by RhoAChristopher P Mack; Fiscal Year: 2012..expression, and we have extended and confirmed these studies by demonstrating that the strong RhoA agonist, sphingosine-1 phosphate, stimulates SMC-specific transcription, that the RhoA effectors mDia1 and mDia2 play a critical ..
- Novel L-threo-sphinganines for ceramides-based cancer therapyBarry J Maurer; Fiscal Year: 2012..All naturally-occurring mammalian dihydroceramides and ceramides utilize 18- carbon (C18) D-erythro-sphinganine/sphingosine backbones, excepting central brain tissues, in which half of ceramides are made on 20-carbon (C20) D-erythro-..
- Metabolites, Sickle Cell Disease, and Novel TherapeuticsYang Xia; Fiscal Year: 2013..an unbiased, high-throughput metabolomic screen that identified several metabolites including adenosine (Ado), sphingosine-1-phosphate (S1P) and 2,3- diphosphoglycerate (2,3-DPG) that are highly elevated in the blood of mice and ..
- The Role of Extrusion in Controlling Epithelial HomeostasisJODY SNOW ROSENBLATT; Fiscal Year: 2013..To do so, the dying cell emits the lipid Sphingosine 1-Phosphate (S1P), which activates extrusion by signaling the S1P receptor 2 (S1P2) in neighboring cells...
- Mitigation of Radiation-Induced Pulmonary Fibrosis by a Sphingosine Kinase InhibiLynn W Maines; Fiscal Year: 2013..g. TNF[unreadable] and TGF[unreadable]) activate sphingomyelinases and ceramidases to produce sphingosine, which is phosphorylated by sphingosine kinases (SK1 and SK2) to produce sphingosine 1-phosphate (S1P)...
- Sphingosine-1-Phosphate, A Novel Mediator of Human Skin Mass Cell FunctionsCarole A Oskeritzian; Fiscal Year: 2010..The sphingolipid metabolite sphingosine-1-phosphate (S1P) is a new addition to the bioactive compounds produced and released by activated mast cells...
- 2012 Glycolipid &Sphingolipid Biology Gordon Research ConferenceWalter M Holleran; Fiscal Year: 2012..as modulators of membrane structure, cell- cell interactions, receptor functions, and signaling via ceramide, sphingosine 1-phosphate and others potent bioactive lipids)...
- Prevention of heart failure and death by sphingolipids: outcomes and mechanisms.JOEL KARLINER; Fiscal Year: 2009..findings from our laboratory and compelling preliminary results support our central hypothesis that the sphingosine kinase/sphingosine 1- phosphate (S1P) pathway is a potent mediator of cardioprotection that can reduce acute ..
- Targeting S1P receptors to prevent hearing lossJerold Chun; Fiscal Year: 2010..Our previous work has demonstrated that sphingosine 1-phosphate (S1P) signaling plays an important role in the maintenance of hair cell integrity...
- Structure Based Design of Humanized Monoclonal Antibodies that Recognize BioactivJONATHAN WOJCIAK; Fiscal Year: 2009..The first bioactive lipid target was sphingosine-1-phosphate (S1P) and our anti-S1P mAbs are in Phase I clinical trials for both cancer and age-related macular ..
- BIOSYNTHESIS OF HUMAN PLATELET GLYCOSPHINGOLIPIDSCHENG TEH WANG; Fiscal Year: 1980..We have shown that the sphingosine composition of human platelet ceramides and glycosphingolipids is different in that the former contain ..
- Sphingosine 1 Phosphate and Embolic StrokeChristian Waeber; Fiscal Year: 2003..This application will explore the hypothesis that a novel system regulating cerebrovascular tone (sphingosine-1-phosphate, its metabolizing enzymes and receptors) can be pharmacologically manipulated in order to ..
- The Role of Sphingolipids in Inflammatory Bowel DiseaseASHLEY SNIDER; Fiscal Year: 2009The broad long-term objective of this proposal is to examine the source sphingosine-1-phosphate (S1P) in the pathology involved in inflammatory bowel disease (IBD), and target its synthetic enzyme, sphingosine kinase 1 (SKI) with ..
- Sphingosine Kinase Inhibitors as Anti-Arthritis AgentsLeo Fitzpatrick; Fiscal Year: 2009..Most importantly, sphingosine 1-phosphate produced by sphingosine kinase (SK) mediates the effects of tumor necrosis factor-1 and interleukin-..
- Autogeneration of an Artery: A Biomimetric StrategyElliot Chaikof; Fiscal Year: 2007..a fibrin gel, provide a useful strategy for the efficient delivery of Fibroblast Growth Factor-2 (FGF-2) and sphingosine-1-phosphate (S1P), as synergistic angiogenic factors...
- Adherens Junction Integrity and Barrier FunctionFred Minnear; Fiscal Year: 2005..Both sphingosine 1-phosphate (S1P) and cAMP-enhancing agents increase barrier function...
- REGULATION OF ENZYME OF LIPID METABOLISMRobert Bell; Fiscal Year: 1990..b>Sphingosine and lysosphingolipids inhibit protein kinase C in vitro...
- HDL-Associated S1P as an Indicator of Relative Risk for Cardiovascular DiseaseKelley M Argraves; Fiscal Year: 2010DESCRIPTION (provided by applicant): The lysosphingolipid, sphingosine 1-phosphate (S1P) is carried in the blood in association with lipoproteins, predominantly high density lipoproteins (HDL)...