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https://www.readbyqxmd.com/read/28434167/analysis-of-s1p-receptor-expression-by-uterine-immune-cells-using-standardized-multi-parametric-flow-cytometry
#1
Jianhong Zhang, Annie Bang, Stephen J Lye
Flow cytometry is a powerful tool for phenotypic and functional analyses of single immune cells. The increasing capability of flow cytometry technology has driven a more detailed understanding of immune cell subsets and functions in complex cellular systems such as the developing human decidua/placenta. We propose a standardized procedure for the isolation and analysis of human decidual natural killer (dNK) cells and this method can be extended to investigation of other uterine lymphocytes. Here this platform is used to examine the expression of sphingosine-1-phosphate (S1P) receptor and functional growth factors by dNK cells...
April 23, 2017: Methods in Molecular Biology
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
#2
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
#3
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/28415564/mammalian-sphingosine-kinase-sphk-isoenzymes-and-isoform-expression-challenges-for-sphk-as-an-oncotarget
#4
REVIEW
Diana Hatoum, Nahal Haddadi, Yiguang Lin, Najah T Nassif, Eileen M McGowan
The various sphingosine kinase (SphK) isoenzymes (isozymes) and isoforms, key players in normal cellular physiology, are strongly implicated in cancer and other diseases. Mutations in SphKs, that may justify abnormal physiological function, have not been recorded. Nonetheless, there is a large and growing body of evidence demonstrating the contribution of gain or loss of function and the imbalance in the SphK/S1P rheostat to a plethora of pathological conditions including cancer, diabetes and inflammatory diseases...
March 18, 2017: Oncotarget
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/28407373/activation-of-the-arabidopsis-membrane-bound-transcription-factor-bzip28-is-mediated-by-site-2-protease-but-not-site-1-protease
#7
Yuji Iwata, Makoto Ashida, Chisa Hasegawa, Kazuki Tabara, Kei-Ichiro Mishiba, Nozomu Koizumi
The unfolded protein response (UPR) is a homeostatic cellular response conserved in eukaryotic cells to alleviate the accumulation of unfolded proteins in the endoplasmic reticulum (ER). Arabidopsis bZIP28 is a membrane-bound transcription factor activated by proteolytic cleavage in response to ER stress, thereby releasing its cytosolic portion containing the bZIP domain from the membrane to translocate into the nucleus where it induces the transcription of genes encoding ER-resident molecular chaperones and folding enzymes...
April 13, 2017: Plant Journal: for Cell and Molecular Biology
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
#8
Elizabeth S Childress, Yugesh Kharel, Anne M Brown, David R Bevan, Kevin R Lynch, Webster L Santos
Sphingosine 1-phosphate (S1P) is a pleiotropic 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 article, we describe the design, synthesis, and biological evaluation of aminothiazole-based guanidine inhibitors of SphK...
April 25, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28400772/sphingolipids-are-dual-specific-drug-targets-for-the-management-of-pulmonary-infections-perspective
#9
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/28396408/size-selective-opening-of-the-blood-brain-barrier-by-targeting-endothelial-sphingosine-1-phosphate-receptor-1
#10
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/28385702/a-shift-in-apom-s1p-between-hdl-particles-in-women-with-type-1-diabetes-mellitus-is-associated-with-impaired-anti-inflammatory-effects-of-the-apom-s1p-complex
#11
Cecilia Frej, Armando J Mendez, Mario Ruiz, Melanie Castillo, Thomas A Hughes, Björn Dahlbäck, Ronald B Goldberg
OBJECTIVE: Type 1 diabetes mellitus (T1D) patients have an increased risk of cardiovascular disease despite high levels of high-density lipoproteins (HDL). Apolipoprotein M (apoM) and its ligand sphingosine 1-phospate (S1P) exert many of the anti-inflammatory effects of HDL. We investigated whether apoM and S1P are altered in T1D and whether apoM and S1P are important for HDL functionality in T1D. APPROACH AND RESULTS: ApoM and S1P were quantified in plasma from 42 healthy controls and 89 T1D patients...
April 6, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28384202/plasma-cross-gestational-sphingolipidomic-analyses-reveal-potential-first-trimester-biomarkers-of-preeclampsia
#12
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/28379469/in-vivo-intrabursal-administration-of-bioactive-lipid-sphingosine-1-phosphate-enhances-vascular-integrity-in-a-rat-model-of-ovarian-hyperstimulation-syndrome-ohss
#13
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
#14
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
#15
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/28373076/fty720-fingolimod-regulates-key-target-genes-essential-for-inflammation-in-microglial-cells-as-defined-by-high-resolution-mrna-sequencing
#16
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
https://www.readbyqxmd.com/read/28369933/sphingolipids-metabolism-in-the-salivary-glands-of-rats-with-obesity-and-streptozotocin-induced-diabetes
#17
Marta Garbowska, Bartłomiej Łukaszuk, Agnieszka Mikłosz, Igor Wróblewski, Krzysztof Kurek, Lucyna Ostrowska, Adrian Chabowski, Małgorzata Żendzian-Piotrowska, Anna Zalewska
BACKGROUNDS: Diabetes is considered a major public health problem affecting millions of individuals worldwide. Remarkably, scientific reports regarding salivary glands sphingolipid metabolism in diabetes are virtually non-existent. This is odd given the well-established link between the both in other tissues (e.g. skeletal muscles, liver) and the key role of these glands in oral health preservation. The aim of this paper is to examine sphingolipids metabolism in the salivary glands in (pre)diabetes (evoked by high fat diet feeding or streptozotocin)...
March 30, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28367448/differential-s1p-receptor-profiles-on-m1-and-m2-polarized-macrophages-affect-macrophage-cytokine-production-and-migration
#18
Jan Müller, Wolfram von Bernstorff, Claus-Dieter Heidecke, Tobias Schulze
Introduction. Macrophages are key players in complex biological processes. In response to environmental signals, macrophages undergo polarization towards a proinflammatory (M1) or anti-inflammatory (M2) phenotype. Sphingosine 1-phosphate (S1P) is a bioactive lysophospholipid that acts via 5 G-protein coupled receptors (S1P1-5) in order to influence a broad spectrum of biological processes. This study assesses S1P receptor expression on macrophages before and after M1 and M2 polarization and performs a comparative analysis of S1P signalling in the two activational states of macrophages...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28364399/sphingosine-1-phosphate-sphingosine-kinase-1-dependent-lymph-node-metastasis-in-esophageal-squamous-cell-carcinoma
#19
Yuta Kawakita, Satoru Motoyama, Yusuke Sato, Souichi Koyota, Akiyuki Wakita, Jiajia Liu, Hajime Saito, Yoshihiro Minamiya
PURPOSE: To establish whether Sphingosine-1-phosphate (S1P) and sphingosine kinase 1 (SphK1) contribute to lymph node metastasis in esophageal squamous cell carcinoma. METHODS: Immunohistochemical analysis of SphK1 expression was performed using a tissue microarray containing 177 thoracic squamous cell esophageal cancer specimens resected at surgery, to investigate the association between intratumoral SphK1 expression and lymph node metastasis. Serum S1P levels and intratumoral SphK1 mRNA and protein expression were also evaluated in mice with vs...
March 31, 2017: Surgery Today
https://www.readbyqxmd.com/read/28364200/sphingosine-1-phosphate-is-involved-in-inflammatory-reactions-in-patients-with-graves-orbitopathy
#20
Yuri Seo, Min Kyung Chae, Sol Ah Han, Eun Jig Lee, Joon H Lee, Jin Sook Yoon
OBJECTIVE: Graves' orbitopathy (GO) is initiated by excessive amount of various inflammatory mediators produced by orbital fibroblasts. This study aimed to assess the crucial role of sphingosine-1-phosphate (S1P) in the inflammatory process of GO. METHODS: Orbital adipose/connective tissue samples were obtained from 10 GO patients and 10 normal control individuals during surgery. Primary orbital fibroblast culture was done. After the expression of S1P receptors and sphingosine kinase (SphK) was assessed with the treatment of interleukin (IL)-1β, we evaluated the expression of pro-inflammatory factors [intercellular adhesion molecule-1 (ICAM-1), cyclooxygenase-2 (COX-2) and IL-6] after treating S1P...
March 31, 2017: Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.]
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