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https://www.readbyqxmd.com/read/29237776/human-naive-and-memory-t-cells-display-opposite-migratory-responses-to-sphingosine-1-phosphate
#1
Annabelle Drouillard, Antoinette Neyra, Anne-Laure Mathieu, Antoine Marçais, Mélanie Wencker, Jacqueline Marvel, Alexandre Belot, Thierry Walzer
The role of sphingosine-1 phosphate (S1P) in leukocyte trafficking has been well deciphered in mice but remains largely unaddressed in humans. In this study, we assessed the ex vivo response to S1P of primary human T cell subsets. We found that tonsil but not blood leukocytes were responsive to S1P gradients, suggesting that T cell responsiveness is regulated during their recirculation in vivo. Tonsil naive T cells were readily chemoattracted by S1P in an FTY720-sensitive, S1PR1-dependent manner. Surprisingly, S1P had the opposite effect on effector memory T cells, resident memory T cells, and recently activated T cells, inhibiting their spontaneous or chemokine-induced migration...
December 13, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29234668/a-genome-wide-screen-for-fty720-sensitive-mutants-reveals-genes-required-for-ros-homeostasis
#2
Kanako Hagihara, Kanako Kinoshita, Kouki Ishida, Shihomi Hojo, Yoshinori Kameoka, Ryosuke Satoh, Teruaki Takasaki, Reiko Sugiura
Fingolimod hydrochloride (FTY720), a sphingosine-1-phosphate (S1P) analogue, is an approved immune modulator for the treatment of multiple sclerosis (MS). Notably, in addition to its well-known mode of action as an S1P modulator, accumulating evidence suggests that FTY720 induces apoptosis in various cancer cells via reactive oxygen species (ROS) generation. Although the involvement of multiple signaling molecules, such as JNK (Jun N-terminal kinase), Akt (alpha serine/threonine-protein kinase) and Sphk has been reported, the exact mechanisms how FTY720 induces cell growth inhibition and the functional relationship between FTY720 and these signaling pathways remain elusive...
November 27, 2017: Microbial Cell
https://www.readbyqxmd.com/read/29233979/extracellular-vesicles-from-human-induced-pluripotent-stem-cell-derived-mesenchymal-stromal-cells-hipsc-mscs-protect-against-renal-ischemia-reperfusion-injury-via-delivering-specificity-protein-sp1-and-transcriptional-activating-of-sphingosine-kinase-1-and
#3
Xiaodong Yuan, Dawei Li, Xiaosong Chen, Conghui Han, Longmei Xu, Tao Huang, Zhen Dong, Ming Zhang
Renal ischemia-reperfusion is a main cause of acute kidney injury (AKI), which is associated with high mortality. Here we show that extracellular vesicles (EVs) secreted from hiPSC-MSCs play a critical role in protection against renal I/R injury. hiPSC-MSCs-EVs can fuse with renal cells and deliver SP1 into target cells, subsequently active SK1 expression and increase S1P formation. Chromatin immunoprecipitation (ChIP) analyses and luciferase assay were used to confirm SP1 binds directly to the SK1 promoter region and promote promoter activity...
December 11, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/29229990/tumor-suppressor-p53-links-ceramide-metabolism-to-dna-damage-response-through-alkaline-ceramidase-2
#4
Ruijuan Xu, Monica Garcia-Barros, Sally Wen, Fang Li, Chih-Li Lin, Yusuf A Hannun, Lina M Obeid, Cungui Mao
p53 mediates the DNA damage response (DDR) by regulating the expression of genes implicated in cell cycle arrest, senescence, programmed cell death (PCD), and metabolism. Herein we demonstrate that human alkaline ceramidase 2 (ACER2) is a novel transcriptional target of p53 and that its transactivation by p53 mediates the DDR. We found that p53 overexpression or its activation by ionizing radiation (IR) upregulated ACER2 in cells. Two putative p53 responsive elements (p53REs) were found in its first intron of the ACER2 gene, and Chromatin Immunoprecipitation (ChIP) assays in combination with promoter activity assays demonstrated that these p53REs are the bona fide p53 binding sites that mediate ACER2 transactivation by p53...
December 11, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29225602/sphingosine-1-phosphate-promotes-the-persistence-of-activated-cd4-t-cells-in-inflamed-sites
#5
Shafqat Ahrar Jaigirdar, Robert A Benson, Aziza Elmesmari, Mariola Stefania Kurowska-Stolarska, Iain B McInnes, Paul Garside, Megan K L MacLeod
Inflammation can be protective or pathogenic depending on context and timeframe. Acute inflammation, including the accumulation of CD4 T cells, accompanies protective immune responses to pathogens, but the presence of activated CD4 T cells at sites of inflammation is associated with chronic inflammatory disease. While significant progress has been made in understanding the migration of CD4 T cells into inflamed sites, the signals that lead to their persistence are poorly characterized. Using a murine ear model of acute inflammation and intravital two-photon imaging, we have dissected the signals that mediate CD4 T cell persistence...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29223361/evidence-suggests-sphingosine-1-phosphate-might-be-actively-generated-degraded-and-transported-to-extracellular-spaces-with-increased-s1p2-and-s1p3-expression-in-colon%C3%A2-cancer
#6
Baasanjav Uranbileg, Takeshi Nishikawa, Hitoshi Ikeda, Makoto Kurano, Masaya Sato, Daisuke Saigusa, Junken Aoki, Toshiaki Watanabe, Yutaka Yatomi
BACKGROUND: A pivotal role of sphingosine 1-phosphate (S1P) in cancer has been suggested based on the ceramide-S1P rheostat theory that the intracellular balance between prosurvival S1P and proapoptotic ceramide determines cell fate. Upregulation of S1P-generating sphingosine kinases (SKs) and downregulation of S1P-degrading S1P lyase (SPL) might increase intracellular S1P levels to exert a prosurvival effect in cancer in general, such as colon cancer. However, we recently observed a distinct S1P metabolism in hepatocellular carcinoma tissues that increased SPL mRNA levels with reduced S1P levels...
November 21, 2017: Clinical Colorectal Cancer
https://www.readbyqxmd.com/read/29221156/the-protective-role-of-sphingosine-1-phosphate-against-the-action-of-the-vascular-disrupting-agent-combretastatin-a-4-3-o-phosphate
#7
Joanna Shepherd, Matthew Fisher, Abigail Welford, Donald M McDonald, Chryso Kanthou, Gillian M Tozer
Solid tumours vary in sensitivity to the vascular disrupting agent combretastatin A-4 3-O-phosphate (CA4P), but underlying factors are poorly understood. The signaling sphingolipid, sphingosine-1-phosphate (S1P), promotes vascular barrier integrity by promoting assembly of VE-cadherin/β-catenin complexes. We tested the hypothesis that tumour pre-treatment with S1P would render tumours less susceptible to CA4P. S1P (1μM) pretreatment attenuated an increase in endothelial cell (HUVEC) monolayer permeability induced by 10μM CA4P...
November 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29218394/modulation-of-sphingosine-1-phosphate-s1p-attenuates-spatial-learning-and-memory-impairments-in-the-valproic-acid-rat-model-of-autism
#8
Hongmei Wu, Quanzhi Zhang, Jingquan Gao, Caihong Sun, Jia Wang, Wei Xia, Yonggang Cao, Yanqiu Hao, Lijie Wu
RATIONALE: Autism spectrum disorders (ASD) are a set of pervasive neurodevelopmental disorders that manifest in early childhood, and it is growing up to be a major cause of disability in children. However, the etiology and treatment of ASD are not well understood. In our previous study, we found that serum levels of sphingosine 1-phosphate (S1P) were increased significantly in children with autism, indicating that S1P levels may be involved in ASD. OBJECTIVE: The objective of this study was to identify a link between increased levels of S1P and neurobehavioral changes in autism...
December 7, 2017: Psychopharmacology
https://www.readbyqxmd.com/read/29216917/unexpected-profile-of-sphingolipid-contents-in-blood-and-bone-marrow-plasma-collected-from-patients-diagnosed-with-acute-myeloid-leukemia
#9
Marzena Wątek, Bonita Durnaś, Tomasz Wollny, Marcin Pasiarski, Stanisław Góźdź, Michał Marzec, Anna Chabowska, Przemysław Wolak, Małgorzata Żendzian-Piotrowska, Robert Bucki
BACKGROUND: Impaired apoptotic pathways in leukemic cells enable them to grow in an uncontrolled way. Moreover, aberrations in the apoptotic pathways are the main factor of leukemic cells drug resistance. METHODS: To assess the presence of potential abnormalities that might promote dysfunction of leukemic cells growth, HPLC system was used to determine sphingosine (SFO), sphinganine (SFA), sphingosine-1-phosphate (S1P) and ceramide (CER) concentration in the blood collected from patients diagnose with acute myeloblastic leukemia (AML; n = 49) and compare to values of control (healthily) group (n = 51)...
December 8, 2017: Lipids in Health and Disease
https://www.readbyqxmd.com/read/29211013/pharmacokinetics-pharmacodynamics-tolerability-and-food-effect-of-cenerimod-a-selective-s1p%C3%A2-receptor-modulator-in-healthy-subjects
#10
Pierre-Eric Juif, Daniela Baldoni, Maribel Reyes, Darren Wilbraham, Salvatore Febbraro, Andrea Vaclavkova, Matthias Hoch, Jasper Dingemanse
The pharmacokinetics, pharmacodynamics, tolerability, and food effect of cenerimod, a potent sphingosine-1-phosphate subtype 1 receptor modulator, were investigated in three sub-studies. Two double-blind, placebo-controlled, randomised studies in healthy male subjects were performed. Cenerimod was administered either as single dose (1, 3, 10 or 25 mg; Study 1) or once daily for 35 days (0.5, 1, 2 or 4 mg; Study 2). A two-period cross-over, open-label study was performed to assess the food effect (1 mg, Study 3)...
December 6, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29208234/vitamin-d-attenuates-sphingosine-1-phosphate-s1p-mediated-inhibition-of-extravillous-trophoblast-migration
#11
Melissa Westwood, Khiria Al-Saghir, Sarah Finn-Sell, Cherlyn Tan, Elizabeth Cowley, Stéphane Berneau, Daman Adlam, Edward D Johnstone
INTRODUCTION: Failure of trophoblast invasion and remodelling of maternal blood vessels leads to the pregnancy complication pre-eclampsia (PE). In other systems, the sphingolipid, sphingosine-1-phosphate (S1P), controls cell migration therefore this study determined its effect on extravillous trophoblast (EVT) function. METHODS: A transwell migration system was used to assess the behaviour of three trophoblast cell lines, Swan-71, SGHPL-4, and JEG3, and primary human trophoblasts in the presence or absence of S1P, S1P pathway inhibitors and 1,25(OH)2D3...
December 2017: Placenta
https://www.readbyqxmd.com/read/29207545/plasma-sphingolipids-in-acute-pancreatitis
#12
Tomasz Konończuk, Bartłomiej Łukaszuk, Małgorzata Żendzian-Piotrowska, Andrzej Dąbrowski, Michalina Krzyżak, Lucyna Ostrowska, Krzysztof Kurek
Acute pancreatitis (AP) is a prevalent gastrointestinal disorder associated with systemic inflammatory response syndrome and, in the case of severe AP, a mortality rate ranging from 36% to 50%. Standard clinical treatment of AP includes intensive hydration, analgesia, and management of complications. Unfortunately, the direct treatment of AP at the level of its molecular pathomechanism has not yet been established. Recent studies indicate that the sphingolipid signaling pathway may be one of the important factors contributing to the development of inflammation in pancreatic diseases...
December 4, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29205338/s1p-receptor-antagonists-fingolimod-and-siponimod-do-not-improve-the-outcome-of-experimental-autoimmune-myasthenia-gravis-mice-after-disease-onset
#13
Andreas Pelz, Hanne Schaffert, Radharani Diallo, Falk Hiepe, Andreas Meisel, Siegfried Kohler
Myasthenia gravis (MG) is an autoimmune disease characterized by muscle weakness and fatigue in the presence of circulating antibodies against components of the neuromuscular junction. Most patients have a good prognosis, but some are refractory to standard-of-care immunosuppressive treatment and suffer from recurrent myasthenic crises. Functional sphingosine-1-phosphate (S1P) antagonists like fingolimod and siponimod (BAF312) are successfully used for the treatment of multiple sclerosis, and fingolimod was shown to prevent the development of myasthenic symptoms in experimental autoimmune myasthenia gravis (EAMG), the standard model of MG...
December 4, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/29193293/functional-antagonism-of-sphingosine-1-phosphate-receptor-1-prevents-cuprizone-induced-demyelination
#14
SunJa Kim, Jacek Bielawski, Hyunmin Yang, Yu Kong, Beiyan Zhou, Jianrong Li
Recent evidence suggests that the oral drug Fingolimod (FTY720) for relapsing-remitting multiple sclerosis (MS) may act directly on the central nervous system (CNS) and modulate disease pathogenesis and progression in experimental models of MS. However, the specific subtype of sphingosine-1-phosphate (S1P) receptors that mediates the effect of FTY720 on the CNS cells has not been fully elucidated. Here, we report that S1P receptor 1 (S1PR1) is elevated in reactive astrocytes in an autoimmunity independent mouse model of MS and that selective S1PR1 modulation is sufficient to ameliorate the loss of oligodendrocytes and demyelination...
November 29, 2017: Glia
https://www.readbyqxmd.com/read/29186783/altered-leukocyte-sphingolipid-pathway-in-breast-cancer
#15
(no author information available yet)
Sphingolipid metabolism pathway is essential in membrane homeostasis, and its dysfunction has been associated with favorable tumor microenvironment, disease progression, and chemotherapy resistance. Its major components have key functions on survival and proliferation, with opposing effects. We have profiled the components of the sphingolipid pathway on leukocytes of breast cancer (BC) patients undergoing chemotherapy treatment and without, including the five sphingosine 1-phosphate (S1P) receptors, the major functional genes, and cytokines, in order to better understand the S1P signaling in the immune cells of these patients...
November 24, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29186197/fingolimod-suppresses-neuronal-autophagy-through-the-mtor-p70s6k-pathway-and-alleviates-ischemic-brain-damage-in-mice
#16
Xiao Li, Ming-Huan Wang, Chuan Qin, Wen-Hui Fan, Dai-Shi Tian, Jun-Li Liu
The bioactive, signaling lipid, sphingosine-1-phosphate (S1P), and its analog, fingolimod (FTY720), have previously shown neuroprotective effects against ischemic brain injury. However, the underlying mechanisms have not yet been fully clarified. The roles of autophagy in ischemic stroke are being increasingly recognized. In the present study, we sought to determine whether the S1P pathway is involved in neuronal autophagy and investigate its possible mechanisms following stroke. Interestingly, we found that FTY720 significantly attenuates infarct volumes and reduces neuronal apoptosis on days 1 and 3 post stroke, accompanied by amelioration of functional deficits...
2017: PloS One
https://www.readbyqxmd.com/read/29185452/dhhc5-mediated-palmitoylation-of-s1p-receptor-subtype-1-determines-g-protein-coupling
#17
Shaymaa Mohamed Mohamed Badawy, Taro Okada, Taketoshi Kajimoto, Takeshi Ijuin, Shun-Ichi Nakamura
Sphingosine 1-phosphate (S1P) is a pleiotropic lipid mediator involved in the regulation of immune cell trafficking and vascular permeability acting mainly through G-protein-coupled S1P receptors (S1PRs). However, mechanism underlying how S1PRs are coupled with G-proteins remains unknown. Here we have uncovered that palmitoylation of a prototypical subtype S1P1R is prerequisite for subsequent inhibitory G-protein (Gi) coupling. We have identified DHHC5 as an enzyme for palmitoylation of S1P1R. Under basal conditions, S1P1R was functionally associated with DHHC5 in the plasma membranes (PM) and was fully palmitoylated, enabling Gi coupling...
November 29, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29183329/surface-display-of-acc-deaminase-on-endophytic-enterobacteriaceae-strains-to-increase-saline-resistance-of-host-rice-sprouts-by-regulating-plant-ethylene-synthesis
#18
Yupei Liu, Lixiang Cao, Hongming Tan, Renduo Zhang
BACKGROUND: Most endophytic bacteria in consortia, which provide robust and broad metabolic capacity, are attractive for applications in plant metabolic engineering. The aim of this study was to investigate the effects of engineered endophytic bacterial strains on rice sprout ethylene level and growth under saline stress. A protocol was developed to synthesize engineered strains by expressing bacterial 1-aminocyclopropane-1-carboxylate (ACC) deaminase gene on cells of endophytic Enterobacter sp...
November 28, 2017: Microbial Cell Factories
https://www.readbyqxmd.com/read/29182993/lymphocyte-count-in-peripheral-blood-is-not-associated-with-the-level-of-clinical-response-to-treatment-with-fingolimod
#19
Yara Dadalti Fragoso, Tim Spelman, Cavit Boz, Raed Alroughani, Alessandra Lugaresi, Steve Vucic, Helmut Butzkueven, Murat Terzi, Eva Havrdova, Dana Horakova, Franco Granella, Javier Olascoaga, José Luis Sánchez-Menoyo, Eugenio Pucci, Michael Barnett, Joseph Bruno B Brooks, Jodi Haartsen
BACKGROUND: Fingolimod is an efficient and safe drug for treating relapsing-remitting multiple sclerosis (RRMS). In vivo, fingolimod is phosphorylated and binds to "sphingosine-1-phosphate"(S1P) receptors that are expressed in a wide range of cells, including lymphocytes. Under the effect of fingolimod, lymphocytes are retained in lymphoid tissues through the regulation of S1P1 receptors. The aim of the present study was to assess whether the degree of lymphopenia was correlated to the positive treatment response of RRMS patients with fingolimod...
November 22, 2017: Multiple Sclerosis and related Disorders
https://www.readbyqxmd.com/read/29180036/sphingosine-1-phosphate-regulates-proliferation-cell-cycle-and-apoptosis-of-hepatocellular-carcinoma-cells-via-syndecan-1
#20
REVIEW
Ye Zeng, Xiaoheng Liu, Zhiping Yan, Linshen Xie
Sphingosine 1-phosphate (S1P) plays important role in hepatocarcinogenesis. We previously demonstrated that S1P induced epithelial-mesenchymal transition of hepatocellular carcinoma (HCC) cells via an MMP-7/Syndecan-1/TGF-β autocrine loop. In the present study, we investigated the regulation role of S1P in cell survival and progression of HCC cells, and tested whether syndecan-1 is required in the S1P action. After transfected with syndecan-1 shRNA, HepG2 and SMMC7721 cells were treated with S1P for 72 h, and then cell proliferation was detected by CCK8 assay, and cell cycle progression and cell apoptosis were detected by flow cytometry...
November 24, 2017: Progress in Biophysics and Molecular Biology
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