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Sphingosine 1 phosphate

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https://www.readbyqxmd.com/read/29773802/cd4-t-cells-are-activated-in-regional-lymph-nodes-and-migrate-to-skin-to-initiate-lymphedema
#1
Gabriela D García Nores, Catherine L Ly, Daniel A Cuzzone, Raghu P Kataru, Geoffrey E Hespe, Jeremy S Torrisi, Jung Ju Huang, Jason C Gardenier, Ira L Savetsky, Matthew D Nitti, Jessie Z Yu, Sonia Rehal, Babak J Mehrara
T cell-mediated responses have been implicated in the development of fibrosis, impaired lymphangiogenesis, and lymphatic dysfunction in secondary lymphedema. Here we show that CD4+ T cells are necessary for lymphedema pathogenesis by utilizing adoptive transfer techniques in CD4 knockout mice that have undergone tail skin and lymphatic excision or popliteal lymph node dissection. We also demonstrate that T cell activation following lymphatic injury occurs in regional skin-draining lymph nodes after interaction with antigen-presenting cells such as dendritic cells...
May 17, 2018: Nature Communications
https://www.readbyqxmd.com/read/29772789/downregulation-of-the-s1p-transporter-spinster-homology-protein-2-spns2-exerts-an-anti-fibrotic-and-anti-inflammatory-effect-in-human-renal-proximal-tubular-epithelial-cells
#2
Olivier Blanchard, Bisera Stepanovska, Manuel Starck, Martin Erhardt, Isolde Römer, Dagmar Meyer Zu Heringdorf, Josef Pfeilschifter, Uwe Zangemeister-Wittke, Andrea Huwiler
Sphingosine kinase (SK) catalyses the formation of sphingosine 1-phosphate (S1P), which acts as a key regulator of inflammatory and fibrotic reactions, mainly via S1P receptor activation. Here, we show that in the human renal proximal tubular epithelial cell line HK2, the profibrotic mediator transforming growth factor β (TGFβ) induces SK-1 mRNA and protein expression, and in parallel, it also upregulates the expression of the fibrotic markers connective tissue growth factor (CTGF) and fibronectin. Stable downregulation of SK-1 by RNAi resulted in the increased expression of CTGF, suggesting a suppressive effect of SK-1-derived intracellular S1P in the fibrotic process, which is lost when SK-1 is downregulated...
May 17, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29769657/correction-to-aryl-hydrocarbon-receptor-signaling-promotes-ormdl3-dependent-generation-of-sphingosine-1-phosphate-by-inhibiting-sphingosine-1-phosphate-lyase
#3
Hsueh-Chun Wang, Tzu-Hsuan Wong, Li-Ting Wang, Hsiang-Han Su, Hsiu-Yueh Yu, Ai-Hsuan Wu, Yu-Chun Lin, Hua-Ling Chen, Jau-Ling Suen, Shih-Hsien Hsu, Li-Chen Chen, Yufeng Zhou, Shau-Ku Huang
In this article, published online 23 March 2018, the affiliation 10 of Zhou Y was incorrect. The affiliation should be "Children's Hospital and Institute of Biomedical Sciences, Fudan University. Key Laboratory of Neonatal Disease, Ministry of Health, 201102, Shanghai, China." The authors regret the errors.
May 16, 2018: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/29766830/impact-of-sphingolipid-mediators-on-determination-of-cochlear-survival-in-ototoxicity
#4
Keiji Tabuchi, Akira Hara
BACKGROUND AND OBJECTIVE: Sphingolipid metabolites, including ceramide, sphingosine, and their phosphorylates (ceramide-1-phosphonate [C1P] and sphingosine-1-phosphate [S1P]), regulate diverse cellular processes including apoptosis, the cell cycle, and cellular differentiation. Recent studies have shown that these sphingolipid metabolites are generated in response to ototoxic agents and play important roles in determining the fate of cochlear hair cells in ototoxic injury. METHODS: This review summarizes the current knowledge on the roles of sphingolipid mediators in cochlear ototoxicity...
May 15, 2018: Current Molecular Pharmacology
https://www.readbyqxmd.com/read/29757216/sphingosine-1-phosphate-receptor-1-is-involved-in-non-obese-diabetic-mouse-thymocyte-migration-disorders
#5
Julia P Lemos, Salete Smaniotto, Carolina V Messias, Otacilio C Moreira, Vinicius Cotta-de-Almeida, Mireille Dardenne, Wilson Savino, Daniella A Mendes-da-Cruz
NOD (non-obese diabetic) mice spontaneously develop type 1 diabetes following T cell-dependent destruction of pancreatic β cells. Several alterations are observed in the NOD thymus, including the presence of giant perivascular spaces (PVS) filled with single-positive (SP) CD4⁺ and CD8⁺ T cells that accumulate in the organ. These cells have a decreased expression of membrane CD49e (the α5 integrin chain of the fibronectin receptor VLA-5 (very late antigen-5). Herein, we observed lower sphingosine-1-phosphate receptor 1 (S1P1) expression in NOD mouse thymocytes when compared with controls, mainly in the mature SP CD4⁺CD62Lhi and CD8⁺CD62Lhi subpopulations bearing the CD49e− phenotype...
May 12, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29750961/apolipoprotein-m-promotes-proliferation-and-invasion-in-non-small-cell-lung-cancers-via-upregulating-s1pr1-and-activating-the-erk1-2-and-pi3k-akt-signaling-pathways
#6
Yifei Zhu, Guanghua Luo, Bo Jiang, Miaomei Yu, Yuehua Feng, Min Wang, Ning Xu, Xiaoying Zhang
Apolipoprotein M (ApoM) is a sphingosine 1-phosphate (S1P) carrier involved in the regulation of S1P. Signaling pathways involving sphingosine kinases (SphKs) and S1P-S1P receptors (S1PRs) play important roles in the oncogenesis of multiple cancers including non-small cell lung cancer (NSCLC). In the present study we have clarified the potential roles of ApoM on the oncogenesis process of NSCLC cells. We detected the ApoM expression in NSCLC tissues and further analyzed its clinical significance. Moreover, we determined effects of ApoM overexpression on tumor cellular behaviours of NSCLC in vitro and in vivo...
May 8, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29749428/accumulation-of-cd69-tissue%C3%A2-resident-memory-t-cells-in-the-nasal-polyps-of-patients-with-chronic-rhinosinusitis
#7
Pascal Ickrath, Norbert Kleinsasser, Xin Ding, Christian Ginzkey, Niklas Beyersdorf, Rudolf Hagen, Thomas Kerkau, Stephan Hackenberg
In patients with chronic rhinosinusitis with nasal polyps (CRSwNP), a relative accumulation of cluster of differentiation (CD)8+ T cells over CD4+ T cells occurs in nasal polyps compared with the peripheral blood. Nasal CD8+ T cells and CD4+ T cells predominantly present an effector memory phenotype. Immunological studies have reported that memory T cells recirculate from the tissues to the peripheral blood and a high percentage of these T cells persist within the tissue. The aim of the present study was to characterize CD69+ sphingosine‑1‑phosphate receptor 1 (S1PR1)‑ tissue resident memory T cells (Trm) in the polyps of patients with CRSwNP...
May 2, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29748384/balance-between-senescence-and-apoptosis-is-regulated-by-telomere-damage-induced-association-between-p16-and-caspase-3
#8
Shanmugam Panneer Selvam, Braden M Roth, Rose Nganga, Jisun Kim, Marion A Cooley, Kristi L Helke, Charles D Smith, Besim Ogretmen
Telomerase activation protects cells from telomere damage by delaying senescence and inducing cell immortalization, whereas telomerase inhibition mediates rapid senescence or apoptosis. However, the cellular mechanisms that determine telomere damage-dependent senescence versus apoptosis induction are largely unknown. Here, we demonstrate that telomerase instability mediated by silencing of sphingosine kinase 2 (SPHK2) and sphingosine 1-phosphate (S1P), which binds and stabilizes telomerase, induces telomere damage-dependent caspase-3 activation and apoptosis, but not senescence, in p16-deficient lung cancer cells or tumors...
May 10, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29743513/sphingosine-kinase-1-associated-autophagy-differs-between-neurons-and-astrocytes
#9
Jose F Moruno-Manchon, Ndidi-Ese Uzor, Chandrashekar R Ambati, Vivekananda Shetty, Nagireddy Putluri, Chinnaswamy Jagannath, Louise D McCullough, Andrey S Tsvetkov
Autophagy is a degradative pathway for removing aggregated proteins, damaged organelles, and parasites. Evidence indicates that autophagic pathways differ between cell types. In neurons, autophagy plays a homeostatic role, compared to a survival mechanism employed by starving non-neuronal cells. We investigated if sphingosine kinase 1 (SK1)-associated autophagy differs between two symbiotic brain cell types-neurons and astrocytes. SK1 synthesizes sphingosine-1-phosphate, which regulates autophagy in non-neuronal cells and in neurons...
May 9, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29740911/the-sphingosine-analog-fingolimod-fty720-enhances-tone-and-contractility-of-rat-gastric-fundus-smooth-muscle
#10
M Kraft, U K Zettl, T Noack, R Patejdl
BACKGROUND: Sphingosine and its metabolite sphingosine phosphate (S1P) regulate a multitude of biological functions, including the contractile state of smooth. Gastrointestinal side effects have been reported in patients treated with FTY720, a sphingosine analog that is approved for the treatment of multiple sclerosis. The aim of this study was to characterize the effects of FTY720 on rat gastric fundus smooth muscle under basal conditions and during activation induced by high-K+ solution...
May 8, 2018: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
https://www.readbyqxmd.com/read/29740670/facile-determination-of-sphingolipids-under-alkali-condition-using-metal-free-column-by-lc-ms-ms
#11
Siddabasave Gowda B Gowda, Kazutaka Ikeda, Makoto Arita
Extraction and analysis of sphingolipids from biological samples is a critical step in lipidomics, especially for minor species such as sphingoid bases and sphingosine-1-phosphate. Although several liquid chromatography-mass spectrometry methods enabling the determination of sphingolipid molecular species have been reported, they were limited in analytical sensitivity and reproducibility by causing significant peak tailing, especially by the presence of phosphate groups, and most of the extraction techniques are laborious and do not cover a broad range of sphingolipid metabolites...
May 9, 2018: Analytical and Bioanalytical Chemistry
https://www.readbyqxmd.com/read/29740092/bile-acids-and-their-respective-conjugates-elicit-different-responses-in-neonatal-cardiomyocytes-role-of-gi-protein-muscarinic-receptors-and-tgr5
#12
Effendi Ibrahim, Ivan Diakonov, Dulasi Arunthavarajah, Teresa Swift, Mary Goodwin, Saraid McIlvride, Vanya Nikolova, Catherine Williamson, Julia Gorelik
Bile acids are recognised as bioactive signalling molecules. While they are known to influence arrhythmia susceptibility in cholestasis, there is limited knowledge about the underlying mechanisms. To delineate mechanisms underlying fetal heart rhythm disturbances in cholestatic pregnancy, we used FRET microscopy to monitor cAMP release and contraction measurements in isolated rodent neonatal cardiomyocytes. The unconjugated bile acids CDCA, DCA and UDCA and, to a lesser extent, CA were found to be relatively potent agonists for the GPBAR1 (TGR5) receptor and elicit cAMP release, whereas all glyco- and tauro- conjugated bile acids are weak agonists...
May 8, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29735920/preanalytical-biases-in-the-measurement-of-human-blood-sphingolipids
#13
Robert Brunkhorst, Waltraud Pfeilschifter, Sammy Patyna, Stefan Büttner, Timon Eckes, Sandra Trautmann, Dominique Thomas, Josef Pfeilschifter, Alexander Koch
Dysregulation of blood sphingolipids is an emerging topic in clinical science. The objective of this study was to determine preanalytical biases that typically occur in clinical and translational studies and that influence measured blood sphingolipid levels. Therefore, we collected blood samples from four healthy male volunteers to investigate the effect of storage conditions (time, temperature, long-term storage, freeze⁻thaw cycles), blood drawing (venous or arterial sampling, prolonged venous compression), and sample preparation (centrifugation, freezing) on sphingolipid levels measured by LC-MS/MS...
May 7, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29735753/metabolism-and-disposition-of-siponimod-a-novel-selective-s1p1-s1p5-agonist-in-healthy-volunteers-and-in-vitro-identification-of-human-cytochrome-p450-enzymes-involved-in-its-oxidative-metabolism
#14
Ulrike Glaenzel, Yi Jin, Robert Nufer, Wenkui Li, Kirsten Schroer, Sylvie Adam-Stitah, Sjoerd Peter van Marle, Eric Legangneux, Hubert Borell, Alexander David James, Axel Meissner, Gian Camenisch, Anne Gardin
Siponimod, a next generation selective sphingosine-1-phosphate receptor modulator, is currently being investigated for the treatment of secondary progressive multiple sclerosis. We investigated the absorption, distribution, metabolism and excretion of a single oral dose of [14 C]siponimod 10 mg in four healthy male subjects. Mass balance, blood and plasma radioactivity, and plasma siponimod concentrations were measured. Metabolite profiles were determined in plasma, urine and feces. Metabolite structures were elucidated using mass spectrometry and comparison with reference compounds...
May 7, 2018: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/29734379/sphingosine-1-phosphate-attenuates-mmp2-and-mmp9-in-human-anaplastic-thyroid-cancer-c643-cells-importance-of-s1p2
#15
Muhammad Yasir Asghar, Kati Kemppainen, Taru Lassila, Kid Törnquist
In anaplastic thyroid cancer C643 cells, sphingosine 1-phosphate (S1P) attenuates migration by activating the S1P2 receptor and the Rho-ROCK pathway. In the present study, we show that stimulating C643 cells with S1P decreases the expression, secretion and activity of matrix metalloproteinase-2 (MMP2), and to a lesser extent MMP9. Using receptor-specific antagonists, and S1P2 siRNA, we showed that the inhibition of expression of MMP2 is mediated through S1P2. Furthermore, S1P inhibited calpain activity, and inhibiting calpain pharmacologically, inhibited the effect of S1P on MMP2 expression and activity, and on MMP9 activity...
2018: PloS One
https://www.readbyqxmd.com/read/29733947/sphingolipid-signaling-modulates-trans-endothelial-cell-permeability-in-dengue-virus-infected-hmec-1-cells
#16
M G Anupriya, Sneha Singh, Neha Vijay Hulyalkar, Easwaran Sreekumar
Dengue has emerged as a major mosquito-borne disease in the tropics and subtropics. In severe dengue, enhanced microvascular endothelial permeability leads to plasma leakage. Direct dengue virus (DENV) infection in human microvascular endothelial cells (HMEC-1) can enhance trans-endothelial leakage. Using a microarray-based analysis, we identified modulation of key endothelial cell signaling pathways in DENV-infected HMEC-1 cells. One among them was the sphingolipid pathway that regulates vascular barrier function...
May 4, 2018: Prostaglandins & Other Lipid Mediators
https://www.readbyqxmd.com/read/29721575/iron-excess-upregulates-spns2-mrna-levels-but-reduces-sphingosine-1-phosphate-export-in-human-osteoblastic-mg-63-cells
#17
L Peltier, C Bendavid, T Cavey, M-L Island, M Doyard, P Leroyer, C Allain, M De Tayrac, M Ropert, O Loréal, P Guggenbuhl
We aimed to study the mechanisms involved in bone-related iron impairment by using the osteoblast-like MG-63 cell line. Our results indicate that iron impact the S1P/S1PR signalizing axis and suggest that iron can affect the S1P process and favor the occurrence of osteoporosis during chronic iron overload. INTRODUCTION: Systemic iron excess favors the development of osteoporosis, especially during genetic hemochromatosis. The cellular mechanisms involved are still unclear despite numerous data supporting a direct effect of iron on bone biology...
May 3, 2018: Osteoporosis International
https://www.readbyqxmd.com/read/29718989/first-evidence-of-sgpl1-expression-in-the-cell-membrane-silencing-the-extracellular-s1p-siren-in-mammary-epithelial-cells
#18
Nadja Engel, Anna Adamus, Marcus Frank, Karin Kraft, Juliane Kühn, Petra Müller, Barbara Nebe, Annika Kasten, Guido Seitz
The bioactive lipid sphingosine-1-phosphate (S1P) is a main regulator of cell survival, proliferation, motility, and platelet aggregation, and it is essential for angiogenesis and lymphocyte trafficking. In that S1P acts as a second messenger intra- and extracellularly, it might promote cancer progression. The main cause is found in the high S1P concentration in the blood, which encourage cancer cells to migrate through the endothelial barrier into the blood vessels. The irreversible degradation of S1P is solely caused by the sphingosine-1-phosphate lyase (SGPL1)...
2018: PloS One
https://www.readbyqxmd.com/read/29713350/sphingosine-1-phosphate-receptor-1-is-required-for-mmp-2-function-in-bone-marrow-mesenchymal-stromal-cells-implications-for-cytoskeleton-assembly-and-proliferation
#19
Chiara Sassoli, Federica Pierucci, Alessia Tani, Alessia Frati, Flaminia Chellini, Francesca Matteini, Ambra Vestri, Giulia Anderloni, Daniele Nosi, Sandra Zecchi-Orlandini, Elisabetta Meacci
Bone marrow-derived mesenchymal stromal cell- (BM-MSC-) based therapy is a promising option for regenerative medicine. An important role in the control of the processes influencing the BM-MSC therapeutic efficacy, namely, extracellular matrix remodelling and proliferation and secretion ability, is played by matrix metalloproteinase- (MMP-) 2. Therefore, the identification of paracrine/autocrine regulators of MMP-2 function may be of great relevance for improving BM-MSC therapeutic potential. We recently reported that BM-MSCs release the bioactive lipid sphingosine 1-phosphate (S1P) and, here, we demonstrated an impairment of MMP-2 expression/release when the S1P receptor subtype S1PR1 is blocked...
2018: Stem Cells International
https://www.readbyqxmd.com/read/29712716/regulation-of-the-metabolism-of-apolipoprotein-m-and-sphingosine-1-phosphate-by-hepatic-ppar%C3%AE-activity
#20
Makoto Kurano, Hitoshi Ikeda, Naoyuki Iso-O, Masumi Hara, Kazuhisa Tsukamoto, Yutaka Yatomi
Apolipoprotein M (apoM) is a carrier and a modulator of sphingosine 1-phosphate (S1P), an important multi-functional bioactive lipid. Since PPARγ is reportedly associated with the function and metabolism of S1P, we investigated the modulation of apoM/S1P homeostasis by PPARγ. First, we investigated the modulation of apoM and S1P homeostasis by the overexpression or knockdown of PPARγ in HepG2 cells and found that both the overexpression and the knockdown of PPARγ decreased apoM expression and S1P synthesis...
April 30, 2018: Biochemical Journal
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