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Sphingosine-1-phosphate

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https://www.readbyqxmd.com/read/28431961/ionizing-radiation-induces-long-term-senescence-in-endothelial-cells-through-mitochondrial-respiratory-complex-ii-dysfunction-and-superoxide-generation
#1
Audrey Lafargue, Charlotte Degorre, Isabelle Corre, Marie-Clotilde Alves-Guerra, Marie-Hélène Gaugler, François Vallette, Claire Pecqueur, François Paris
Ionizing radiation causes oxidative stress, leading to acute and late cellular responses. We previously demonstrated that irradiation of non-proliferating endothelial cells, as observed in normal tissues, induces early apoptosis, which can be inhibited by pretreatment with Sphingosine-1-Phosphate. We now propose to better characterize the long-term radiation response of endothelial cells by studying the molecular pathways associated with senescence and its link with acute apoptosis. First, senescence was validated in irradiated quiescent microvascular HMVEC-L in a dose- and time-dependent manner by SA β-galactosidase staining, p16(Ink4a) and p21(Waf1) expression, pro-inflammatory IL-8 secretion and DNA damage response activation...
April 18, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28422187/a-sphingosine-1-phosphate-receptor-1-agonist-inhibits-tertiary-lymphoid-tissue-reactivation-and-hypersensitivity-in-the-lung
#2
C A Huppé, P Blais Lecours, A Lechasseur, D R Gendron, A M Lemay, E Y Bissonnette, M R Blanchet, C Duchaine, M C Morissette, H Rosen, D Marsolais
Hypersensitivity pneumonitis is characterized by pulmonary accumulation of B-cell-rich tertiary lymphoid tissues (TLTs), which are alleged sites of amplification for antigen-specific responses. The sphingosine-1-phosphate receptor 1 (S1P1) regulates key mechanisms underlying lymphoid tissue biology and its chemical modulation causes lymphocyte retention in lymph nodes. Given the putative immunopathogenic impact of lymphocyte accumulation in TLTs, we investigated whether or not chemical modulation of S1P1 caused lymphocyte retention within TLTs in a model of hypersensitivity pneumonitis...
April 19, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28420720/a-phase-i-study-of-abc294640-a-first-in-class-sphingosine-kinase-2-inhibitor-in-patients-with-advanced-solid-tumors
#3
Carolyn D Britten, Melanie B Thomas, Elizabeth Garrett-Mayer, Steven H Chin, Keisuke Shirai, Besim Ogretmen, Tricia A Bentz, Alan Brisendine, Kate Anderton, Susan L Cusack, Lynn W Maines, Yan Zhuang, Charles D Smith
Purpose:  Sphingosine kinases (SK1 and SK2) regulate tumor growth by generating the mitogenic and pro-inflammatory lipid sphingosine 1-phosphate (S1P). This phase I study investigated the safety, pharmacokinetics, pharmacodynamics and anti-tumor activity of ABC294640, a first-in-class orally-available inhibitor of SK2.  <p>Experimental Design:  Escalating doses of ABC294640 were administered orally to patients with advanced solid tumors in sequential cohorts at the following dose levels: 250 mg qd, 250 mg bid, 500 mg bid and 750 mg bid, continuously in cycles of 28 days...
April 18, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28418499/sphingosine-1-phosphate-s1p-related-response-of-human-conjunctival-fibroblasts-after-filtration-surgery-for-glaucoma
#4
Yuka Aoyama-Araki, Megumi Honjo, Takatoshi Uchida, Reiko Yamagishi, Kuniyuki Kano, Junken Aoki, Makoto Aihara
Purpose: To investigate levels of sphingosine-1-phosphate (S1P) in aqueous fluid samples taken before and after filtration surgery and S1P-induced human conjunctival fibroblast (HCF) responses. Methods: Levels of S1P and its related sphingophospholipids in aqueous fluid obtained immediately before and after filtration surgery were determined by liquid chromatography-tandem mass spectrometry. HCFs were used for all in vitro experiments. The expression of five S1P receptor subtypes in HCFs was examined by quantitative real-time PCR...
April 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28409823/an-s1p1-agonist-asp4058-suppresses-intracranial-aneurysm-through-promoting-endothelial-integrity-and-blocking-macrophage-transmigration
#5
Rie Yamamoto, Tomohiro Aoki, Hirokazu Koseki, Miyuki Fukuda, Jun Hirose, Keiichi Tsuji, Katsumi Takizawa, Shinichiro Nakamura, Haruka Miyata, Nozomu Hamakawa, Hidetoshi Kasuya, Kazuhiko Nozaki, Yoshitaka Hirayama, Ichiro Aramori, Shuh Narumiya
BACKGROUND AND PURPOSE: Intracranial aneurysm (IA), common in general public, causes lethal subarachnoid hemorrhage on rupture. Prevention of rupture of IA is therefore socially important. However, there is currently no medical treatment. Recent studies suggest that IA is a disease of chronic inflammation in the arterial wall caused by endothelial dysfunction and infiltrated macrophages. Sphingosine-1-phosphate receptor type 1 (S1P1 ) is present on the endothelium and promotes its barrier function...
April 13, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28409209/2-acetyl-5-tetrahydroxybutyl-imidazole-thi-protects-661w-cells-against-oxidative-stress
#6
Carlotta Fabiani, Aida Zulueta, Fabiola Bonezzi, Josefina Casas, Riccardo Ghidoni, Paola Signorelli, Anna Caretti
Retinal degeneration and in particular retinitis pigmentosa (RP) is associated to ceramide (Cer) accumulation and cell death induction. Cer and sphingosine-1-phosphate (S1P) belong to the sphingolipids class and exert a pro-apoptotic and pro-survival activity, respectively. Our aim is to target sphingolipid metabolism by inhibiting S1P lyase that regulates one of the S1P degradation pathways, to reduce retinal photoreceptor damage. The murine 661W cone-like cell line was pretreated with THI, an inhibitor of S1P lyase and exposed to H2O2-induced oxidative stress...
April 13, 2017: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/28406646/transforming-sphingosine-kinase-1-inhibitors-into-dual-and-sphingosine-kinase-2-selective-inhibitors-design-synthesis-and-in-vivo-activity
#7
Elizabeth S Childress, Yugesh Kharel, Anne M Brown, David R Bevan, Kevin R Lynch, Webster L Santos
Sphingosine 1-phosphate (S1P) is a pleotropic signaling molecule that interacts with its five G-protein coupled receptors S1P1-5 to regulate cell growth and survival and has been implicated in a variety of diseases including cancer and sickle cell disease. As the key mediators in the synthesis of S1P, sphingosine kinase (SphK) isoforms 1 and 2 have attracted attention as viable targets for pharmaceutical inhibition. In this report, we describe the design, synthesis, and biological evaluation of aminothiazole-based guanidine inhibitors of SphK...
April 13, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28400772/sphingolipids-are-dual-specific-drug-targets-for-the-management-of-pulmonary-infections-perspective
#8
REVIEW
Lalita Sharma, Hridayesh Prakash
Sphingolipids are the major constituent of the mucus secreted by the cells of epithelial linings of lungs where they maintain the barrier functions and prevent microbial invasion. Sphingolipids are interconvertible, and their primary and secondary metabolites have both structural and functional roles. Out of several sphingolipid metabolites, sphingosine-1 phosphate (S1P) and ceramide are central molecules and decisive for sphingolipid signaling. These are produced by enzymatic activity of sphingosine kinase-1 (SK-1) upon the challenge with either biological or physiological stresses...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28399143/sphingosine-1-phosphate-receptor-1-s1pr1-agonist-cym5442-inhibits-expression-of-intracellular-adhesion-molecule-1-icam1-in-endothelial-cells-infected-with-influenza-a-viruses
#9
Hao Jiang, Si-Mei Shen, Jie Yin, Peng-Peng Zhang, Yi Shi
BACKGROUND: Influenza A virus infection and its complications effect a large population worldwide. Endothelial cells are an important component in lung inflammation caused by influenza A virus infection. The roles of endothelial sphingosine 1-phophate receptor 1 (S1PR1) in the regulation of molecules involved in leukocyte recruitment during influenza A virus infection still remain unknown. In this report, we tested our hypothesis that S1PR1 agonist CYM5442 inhibits expression of intracellular adhesion molecules 1 (ICAM1) in endothelial cells infected with influenza A virus...
2017: PloS One
https://www.readbyqxmd.com/read/28398597/results-from-the-first-in-human-study-with-ozanimod-a-novel-selective-sphingosine-1-phosphate-receptor-modulator
#10
Jonathan Q Tran, Jeffrey P Hartung, Robert J Peach, Marcus F Boehm, Hugh Rosen, Heather Smith, Jennifer L Brooks, Gregg A Timony, Allan D Olson, Sheila Gujrathi, Paul A Frohna
The sphingosine-1-phosphate 1 receptor (S1P1R ) is expressed by lymphocytes, dendritic cells, and vascular endothelial cells and plays a role in the regulation of chronic inflammation and lymphocyte egress from peripheral lymphoid organs. Ozanimod is an oral selective modulator of S1P1R and S1P5R receptors in clinical development for the treatment of chronic immune-mediated, inflammatory diseases. This first-in-human study characterized the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of ozanimod in 88 healthy volunteers using a range of single and multiple doses (7 and 28 days) and a dose-escalation regimen...
April 11, 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28396408/size-selective-opening-of-the-blood-brain-barrier-by-targeting-endothelial-sphingosine-1-phosphate-receptor-1
#11
Keisuke Yanagida, Catherine H Liu, Giuseppe Faraco, Sylvain Galvani, Helen K Smith, Nathalie Burg, Josef Anrather, Teresa Sanchez, Costantino Iadecola, Timothy Hla
The vasculature of the central nervous system (CNS) forms a selective barrier termed the blood-brain barrier (BBB). Disruption of the BBB may contribute to various CNS diseases. Conversely, the intact BBB restricts efficient penetration of CNS-targeted drugs. Here, we report the BBB-regulatory role of endothelial sphingosine 1-phosphate (S1P) receptor-1, a G protein-coupled receptor known to promote the barrier function in peripheral vessels. Endothelial-specific S1pr1 knockout mice (S1pr1(iECKO) ) showed BBB breach for small-molecular-mass fluorescence tracers (<3 kDa), but not larger tracers (>10 kDa)...
April 10, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28392482/adult-stem-cells-in-psychiatric-disorders-new-discoveries-in-peripheral-blood
#12
REVIEW
Jolanta Kucharska-Mazur, Marcin Jabłoński, Błażej Misiak, Dorota Frydecka, Janusz Rybakowski, Mariusz Z Ratajczak, Jerzy Samochowiec
The new area of research in psychiatric disorders is concerned with abnormal regeneration processes. The role of brain neurogenesis has been studied for decades. New discoveries, concerned with the pluripotency of VSEL cells and the role of factors involved in stem cell trafficking in peripheral blood create hope that it will be possible to develop a better understanding of the processes of neuroregeneration/neurodegeneration. There is an ongoing research investigating concentrations of: sphingosine -1-phosphate, SDF-1, elements of complement cascade, and stem cells in peripheral blood, including their possible connection to psychiatric disorders...
April 7, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/28384202/plasma-cross-gestational-sphingolipidomic-analyses-reveal-potential-first-trimester-biomarkers-of-preeclampsia
#13
Aneta Dobierzewska, Sony Soman, Sebastian E Illanes, Andrew J Morris
INTRODUCTION: Preeclampsia (PE) is a gestational disorder, manifested in the second half of pregnancy by maternal hypertension, proteinuria and generalized edema. PE is a major cause of maternal and fetal morbidity and mortality, accounting for nearly 40% of all premature births worldwide. Bioactive sphingolipids are emerging as key molecules involved in etiopathogenesis of PE, characterized by maternal angiogenic imbalance and symptoms of metabolic syndrome. The aim of this study was to compare the cross-gestational profile of circulating bioactive sphingolipids in maternal plasma from preeclamptic (PE) versus normotensive control (CTL) subjects with the goal of identifying sphingolipids as candidate first trimester biomarkers of PE for early prediction of the disease...
2017: PloS One
https://www.readbyqxmd.com/read/28382862/inflammatory-bowel-disease-new-therapeutic-options-in-the-post-anti-tnf%C3%AE-era
#14
Miguel Jiménez Pérez, Raúl V Olmedo Martín, Víctor M Amo Trillo, Rocío González Gande
Inflammatory bowel diseasesare chronic bowel disorders the causes of which have not been fully elucidated,though they all sharean immunological basis. They have an important impact on both quality of life of the patient and on healthcare services. The incorporation of biological agents against tumour necrosis factor (TNF) alpha some 15 years ago represented a revolution in the management of patients with disease that did not respond to conventional treatment, enabling an overall improvement in the quality of life of many of these patients...
April 6, 2017: Current Drug Metabolism
https://www.readbyqxmd.com/read/28381169/the-role-of-sphingosine-1-phosphate-in-the-tumor-microenvironment-and-its-clinical-implications
#15
REVIEW
Masato Nakajima, Masayuki Nagahashi, Omar M Rashid, Kazuaki Takabe, Toshifumi Wakai
Elucidating the interaction between cancer and non-cancer cells, such as blood vessels, immune cells, and other stromal cells, in the tumor microenvironment is imperative in understanding the mechanisms underlying cancer progression and metastasis, which is expected to lead to the development of new therapeutics. Sphingosine-1-phosphate is a bioactive lipid mediator that promotes cell survival, proliferation, migration, angiogenesis/lymphangiogenesis, and immune responsiveness, which are all factors involved in cancer progression...
April 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28379469/in-vivo-intrabursal-administration-of-bioactive-lipid-sphingosine-1-phosphate-enhances-vascular-integrity-in-a-rat-model-of-ovarian-hyperstimulation-syndrome-ohss
#16
Mariana Di Pietro, Natalia Pascuali, Leopoldina Scotti, Griselda Irusta, Diana Bas, María May, Marta Tesone, Dalhia Abramovich, Fernanda Parborell
STUDY QUESTION: Can the bioactive lipid sphingosine-1 phosphate (S1P) act as an endothelial barrier-enhancing molecule and, in turn, restore the vascular integrity and homeostasis in a rat model of ovarian hyperstimulation syndrome (OHSS). STUDY ANSWER: In vivo administration of S1P may prevent the early onset of OHSS and decrease its severity. WHAT IS KNOWN ALREADY: Although advances in the prediction and treatment of OHSS have been made, complete prevention has not been possible yet...
April 1, 2017: Molecular Human Reproduction
https://www.readbyqxmd.com/read/28377994/data-on-subgroup-specific-baseline-characteristics-and-serum-sphingosine-1-phosphate-concentrations-in-the-study-of-health-in-pomerania
#17
Eileen Moritz, Danilo Wegner, Stefan Groß, Martin Bahls, Marcus Dörr, Stephan B Felix, Till Ittermann, Stefan Oswald, Matthias Nauck, Nele Friedrich, Rainer H Böger, Günter Daum, Edzard Schwedhelm, Bernhard H Rauch
In this data article, we provide subgroup specific baseline characteristics and serum sphingosine-1-phosphate (S1P) concentrations for healthy individuals within the Study of Health in Pomerania (SHIP)-TREND cohort. After exclusion of subjects with cardiovascular disease, diabetes mellitus, hypertension, metabolic syndrome, elevated liver enzymes and/or chronic kidney disease stadium III or IV, four subgroups were defined according to different limits for body mass index (BMI), alterations in blood lipid levels and smoking status...
June 2017: Data in Brief
https://www.readbyqxmd.com/read/28377281/novel-sphingosine-kinase-1-inhibitor-lcl351-reduces-immune-responses-in-murine-dss-induced-colitis
#18
Michael J Pulkoski-Gross, Joachim D Uys, K Alexa Orr-Gandy, Nicolas Coant, Agnieszka B Bialkowska, Zdzislaw M Szulc, Aiping Bai, Alicja Bielawska, Danyelle M Townsend, Yusuf A Hannun, Lina M Obeid, Ashley J Snider
Sphingosine-1-phosphate (S1P) is a biologically active sphingolipid metabolite which has been implicated in many diseases including cancer and inflammatory diseases. Recently, sphingosine kinase 1 (SK1), one of the isozymes which generates S1P, has been implicated in the development and progression of inflammatory bowel disease (IBD). Based on our previous work, we set out to determine the efficacy of a novel SK1 selective inhibitor, LCL351, in a murine model of IBD. LCL351 selectively inhibits SK1 both in vitro and in cells...
April 2, 2017: Prostaglandins & Other Lipid Mediators
https://www.readbyqxmd.com/read/28375547/demyelination-induced-by-oxidative-stress-is-regulated-by-sphingosine-1-phosphate-receptors
#19
Sinead A O'Sullivan, Maria Velasco-Estevez, Kumlesh K Dev
Oxidative stress is a pathological condition defined as an imbalance between production and removal of reactive oxygen species. This process causes structural cell damage, disrupts DNA repair and induces mitochondrial dysfunction. Many in vitro studies have used direct bolus application of H2 O2 to investigate the role of oxidative stress in cell culture. In this study, using mouse organotypic cerebellar slice cultures, the effects of H2 O2 -induced oxidative stress on myelination state were examined, using bolus concentrations of H2 O2 (0...
April 4, 2017: Glia
https://www.readbyqxmd.com/read/28373076/fty720-fingolimod-regulates-key-target-genes-essential-for-inflammation-in-microglial-cells-as-defined-by-high-resolution-mrna-sequencing
#20
Amitabh Das, Sarder Arifuzzaman, Sun Hwa Kim, Young Seek Lee, Kyoung Hwa Jung, Young Gyu Chai
Although microglial cells have an essential role in the host defense of the brain, the abnormal activation of microglia can lead to devastating outcomes, such as neuroinflammation and neurodegeneration. Emerging evidence indicates that FTY720 (fingolimod), an FDA-approved drug, has beneficial effects on brain cells in the central nervous system (CNS) and, more recently, immunosuppressive activities in microglia via modulation of the sphingosine 1 phosphate (S1P) 1 receptor. However, the exact molecular aspects of FTY720 contribution in microglia remain largely unaddressed...
March 31, 2017: Neuropharmacology
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