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https://www.readbyqxmd.com/read/29286094/sphingosine-1-phosphate-ameliorates-the-cardiac-hypertrophic-response-through-inhibiting-the-activity-of-histone-deacetylase-2
#1
Hui Yan, Shaowei Yi, Hang Zhuang, Lujin Wu, Dao Wen Wang, Jiangang Jiang
Inhibition of histone deacetylase-2 (HDAC2), which is a prohypertrophic factor in the heart, can functionally attenuate cardiac hypertrophy. The present study aimed to investigate whether sphingosine‑1‑phosphate (S1P), which has recently been reported to suppress HDAC2 activity, could ameliorate the cardiac hypertrophic response and improve cardiac function in mice with transverse aortic constriction (TAC), as well as to determine the underlying mechanisms. Briefly, 8‑week‑old male C57BL/6 mice were randomly divided into sham, TAC and TAC + S1P groups; the results indicated that S1P treatment attenuated TAC‑induced cardiac dysfunction...
December 15, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29249563/design-and-synthesis-of-pyrazolopyridine-derivatives-as-sphingosine-1-phosphate-receptor-2-ligands
#2
Zonghua Luo, Xuyi Yue, Hao Yang, Hui Liu, Robyn S Klein, Zhude Tu
Eleven new sphingosine 1-phosphate receptor 2 (S1PR2) ligands were synthesized by modifying lead compound N-(2,6-dichloropyridin-4-yl)-2-(4-isopropyl-1,3-dimethyl-1H-pyrazolo[3,4-b]pyridin-6-yl)hydrazine-1-carboxamide (JTE-013) and their binding affinities toward S1PRs were determined in vitro using [32P]S1P and cell membranes expressing recombinant human S1PRs. Among these ligands, 35a (IC50 = 29.1 ± 2.6 nM) and 35b (IC50 = 56.5 ± 4.0 nM) exhibit binding potency toward S1PR2 comparable to JTE-013 (IC50 = 58...
December 6, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29237776/human-naive-and-memory-t-cells-display-opposite-migratory-responses-to-sphingosine-1-phosphate
#3
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/29208234/vitamin-d-attenuates-sphingosine-1-phosphate-s1p-mediated-inhibition-of-extravillous-trophoblast-migration
#4
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/29168342/sphingosine-1-phosphate-s1p-enhances-glomerular-endothelial-cells-activation-mediated-by-anti-myeloperoxidase-antibody-positive-igg
#5
Xiao-Jing Sun, Min Chen, Ming-Hui Zhao
Cumulating evidences suggested an important role of sphingosine-1-phosphate (S1P) and its receptors in regulating endothelial barrier integrity. Our previous study revealed that the circulating S1P levels and renal expression of S1PRs correlated with disease activity and renal damage in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). This study investigated the role of S1P and its receptors in myeloperoxidase (MPO)-ANCA-positive IgG-mediated glomerular endothelial cell (GEnC) activation...
November 23, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29138832/effect-of-moesin-phosphorylation-on-high%C3%A2-dose-sphingosine%C3%A2-1%C3%A2-phosphate%C3%A2-induced-endothelial-responses
#6
Yan Xiao, Jie Wu, Yongjun Yuan, Xiaohua Guo, Bo Chen, Qiaobing Huang
It was previously reported that low‑dose sphingosine‑1‑phosphate (S1P) enhanced endothelial barrier integrity, whereas high‑dose S1P induced endothelial monolayer hyperpermeability responses. A number of studies have revealed the underlying molecular mechanisms of the physiological‑dose of S1P on barrier‑protective effect. However, little work has been performed to determine the effect of S1P‑induced endothelial barrier responses. In the present study, the role of moesin phosphorylation in excessive S1P‑induced endothelial hyperpermeability was investigated by western blotting, fluorescence staining and transendothelial electrical resistance detection...
November 13, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29130028/sphingosine-kinases-sphingosine-1-phosphate-signaling-in-hepatic-lipid-metabolism
#7
Eric K Kwong, Xiaojiaoyang Li, Phillip B Hylemon, Huiping Zhou
The ever-increasing prevalence of metabolic diseases such as dyslipidemia and diabetes in the western world continues to be of great public health concern. Biologically active sphingolipids, such as sphingosine 1-phosphate (S1P) and ceramide, are important regulators of lipid metabolism. S1P not only directly functions as an active intracellular mediator, but also activates multiple signaling pathways via five transmembrane G-protein coupled receptors (GPCRs), S1PR1-5. S1P is exclusively formed by sphingosine kinases (SphKs)...
August 2017: Current Pharmacology Reports
https://www.readbyqxmd.com/read/29123941/bile-acids-as-global-regulators-of-hepatic-nutrient-metabolism
#8
Phillip B Hylemon, Kazuaki Takabe, Mikhail Dozmorov, Masayuki Nagahashi, Huiping Zhou
Bile acids (BA) are synthesized from cholesterol in the liver. They are essential for promotion of the absorption of lipids, cholesterol, and lipid-soluble vitamins from the intestines. BAs are hormones that regulate nutrient metabolism by activating nuclear receptors (farnesoid X receptor (FXR), pregnane X receptor, vitamin D) and G protein-coupled receptors (e.g., TGR5, sphingosine-1-phosphate receptor 2 (S1PR2)) in the liver and intestines. In the liver, S1PR2 activation by conjugated BAs activates the extracellular signal-regulated kinase 1/2 and AKT signaling pathways, and nuclear sphingosine kinase 2...
June 2017: Liver Research
https://www.readbyqxmd.com/read/29100348/changes-of-foxo3a-in-pbmcs-and-its-associations-with-stress-hyperglycemia-in-acute-obstructive-suppurative-cholangitis-patients
#9
Niu Bailin, Chen Nan, Li Peizhi, He Kun, Zhu Xiwen, Ren Guosheng, Gong Jianping, Zhang Wenfeng
Objective: The levels of Foxo3a in the peripheral blood mononuclears cells (PBMCs) before and after treatment were detected in acute obstructive suppurative cholangitis (AOSC) patients to evaluate the associations between Foxo3a and stress hyperglycemia (SHG). Methods: PBMCs were obtained from AOSC patients (n=28) on admission (AP), from patients at 1 week after cure (RP) and from healthy volunteers (HV) (n=14) to evaluate the relationship between the protein levels of Foxo3a and the serum levels of glucose...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29093479/bile-acid-tudca-improves-insulin-clearance-by-increasing-the-expression-of-insulin-degrading-enzyme-in-the-liver-of-obese-mice
#10
Jean Franciesco Vettorazzi, Mirian Ayumi Kurauti, Gabriela Moreira Soares, Patricia Cristine Borck, Sandra Mara Ferreira, Renato Chaves Souto Branco, Luciana de Souza Lima Michelone, Antonio Carlos Boschero, Jose Maria Costa Junior, Everardo Magalhães Carneiro
Disruption of insulin secretion and clearance both contribute to obesity-induced hyperinsulinemia, though reduced insulin clearance seems to be the main factor. The liver is the major site for insulin degradation, a process mainly coordinated by the insulin-degrading enzyme (IDE). The beneficial effects of taurine conjugated bile acid (TUDCA) on insulin secretion as well as insulin sensitivity have been recently described. However, the possible role of TUDCA in insulin clearance had not yet been explored. Here, we demonstrated that 15 days treatment with TUDCA reestablished plasma insulin to physiological concentrations in high fat diet (HFD) mice, a phenomenon associated with increased insulin clearance and liver IDE expression...
November 1, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28990561/-cholestasis-induced-liver-injury-the-role-of-s1pr2
#11
Louise Dissous, Elizabeth Cesard, Arnaud Dance, Thierry Tordjmann
No abstract text is available yet for this article.
June 2017: Médecine Sciences: M/S
https://www.readbyqxmd.com/read/28970286/obesity-stimulated-aldosterone-release-is-not-related-to-an-s1p-dependent-mechanism
#12
Stephan Werth, Helge Müller-Fielitz, Walter Raasch
Aldosterone has been identified as an important factor in obesity-associated hypertension. Here, we investigated whether sphingosine-1-phosphate (S1P), which has previously been linked to obesity, increases aldosterone release. S1P-induced aldosterone release was determined in NCI H295R cells in the presence of S1P receptor (S1PR) antagonists. In vivo release of S1P (100-300 µg/kgbw) was investigated in pithed, lean Sprague Dawley (SD) rats, diet-obese spontaneous hypertensive rats (SHRs), as well as in lean or obese Zucker rats...
December 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28954861/the-balance-between-g%C3%AE-i-cdc42-rac-and-g%C3%AE-12-13-rhoa-pathways-determines-endothelial-barrier-regulation-by-sphingosine-1-phosphate
#13
Nathalie R Reinhard, Marieke Mastop, Taofei Yin, Yi Wu, Esmeralda K Bosma, Theodorus W J Gadella, Joachim Goedhart, Peter L Hordijk
The bioactive sphingosine-1-phosphatephosphate (S1P) is present in plasma, bound to carrier proteins, and involved in many physiological processes, including angiogenesis, inflammatory responses, and vascular stabilization. S1P can bind to several G-protein-coupled receptors (GPCRs) activating a number of different signaling networks. At present, the dynamics and relative importance of signaling events activated immediately downstream of GPCR activation are unclear. To examine these, we used a set of fluorescence resonance energy transfer-based biosensors for different RhoGTPases (Rac1, RhoA/B/C, and Cdc42) as well as for heterotrimeric G-proteins in a series of live-cell imaging experiments in primary human endothelial cells...
November 7, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28949776/beneficial-effects-of-bile-acid-receptor-agonists-in-pulmonary-disease-models
#14
REVIEW
Paolo Comeglio, Annamaria Morelli, Luciano Adorini, Mario Maggi, Linda Vignozzi
Bile acids act as steroid hormones, controlling lipid, glucose and energy metabolism, as well as inflammation and fibrosis. Their actions are implemented through activation of nuclear (FXR, VDR, PXR) and membrane G protein-coupled (TGR5, S1PR2) receptors. Areas covered: This review discusses the potential of FXR and TGR5 as therapeutic targets in the treatment of pulmonary disorders linked to metabolism and/or inflammation. Obeticholic acid (OCA) is the most clinically advanced bile acid-derived agonist for FXR-mediated anti-inflammatory and anti-fibrotic effects...
November 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28943240/control-of-cell-shape-neurite-outgrowth-and-migration-by-a-nogo-a-hspg-interaction
#15
Anissa Kempf, Enrica Boda, Jessica C F Kwok, Rafael Fritz, Valentina Grande, Andrea M Kaelin, Zorica Ristic, Andre Schmandke, Antonio Schmandke, Bjoern Tews, James W Fawcett, Olivier Pertz, Annalisa Buffo, Martin E Schwab
Heparan sulfate proteoglycans (HSPGs) critically modulate adhesion-, growth-, and migration-related processes. Here, we show that the transmembrane protein, Nogo-A, inhibits neurite outgrowth and cell spreading in neurons and Nogo-A-responsive cell lines via HSPGs. The extracellular, active 180 amino acid Nogo-A region, named Nogo-A-Δ20, binds to heparin and brain-derived heparan sulfate glycosaminoglycans (GAGs) but not to the closely related chondroitin sulfate GAGs. HSPGs are required for Nogo-A-Δ20-induced inhibition of adhesion, cell spreading, and neurite outgrowth, as well as for RhoA activation...
October 9, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28878352/s1pr1-drives-a-feed-forward-signalling-loop-to-regulate-batf3-and-the-transcriptional-programme-of-hodgkin-lymphoma-cells
#16
K Vrzalikova, M Ibrahim, M Vockerodt, T Perry, S Margielewska, L Lupino, E Nagy, E Soilleux, D Liebelt, R Hollows, A Last, G Reynolds, M Abdullah, H Curley, M Care, D Krappmann, R Tooze, J Allegood, S Spiegel, W Wei, C B J Woodman, P G Murray
The Hodgkin/Reed-Sternberg (HRS) cells of classical Hodgkin lymphoma (HL) are characterised by the aberrant activation of multiple signalling pathways. Here we show that a subset of HL displays altered expression of sphingosine-1-phosphate (S1P) receptors (S1PR). S1P activates phosphatidylinositide 3-kinase (PI3-K) in these cells that is mediated by the increased expression of S1PR1 and the decreased expression of S1PR2. We also showed that genes regulated by PI3-K signalling pathway in HL cell lines significantly overlap with the transcriptional programme of primary HRS cells...
September 7, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28725183/bile-acid-mediated-sphingosine-1-phosphate-receptor-2-signaling-promotes-neuroinflammation-during-hepatic-encephalopathy-in-mice
#17
Matthew McMillin, Gabriel Frampton, Stephanie Grant, Shamyal Khan, Juan Diocares, Anca Petrescu, Amy Wyatt, Jessica Kain, Brandi Jefferson, Sharon DeMorrow
Hepatic encephalopathy (HE) is a neuropsychiatric complication that occurs due to deteriorating hepatic function and this syndrome influences patient quality of life, clinical management strategies and survival. During acute liver failure, circulating bile acids increase due to a disruption of the enterohepatic circulation. We previously identified that bile acid-mediated signaling occurs in the brain during HE and contributes to cognitive impairment. However, the influences of bile acids and their downstream signaling pathways on HE-induced neuroinflammation have not been assessed...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28676392/s1pr2-antagonist-protects-endothelial-cells-against-high-glucose-induced-mitochondrial-apoptosis-through-the-akt-gsk-3%C3%AE-signaling-pathway
#18
Hengdao Liu, Hui Peng, Shuhua Chen, Yanwei Liu, Hong Xiang, Ruifang Chen, Wei Chen, Shaoli Zhao, Pan Chen, Hongwei Lu
Vascular complications are the main cause of morbidity and mortality associated with type 2 diabetes mellitus. An early hallmark of the onset of vascular complications is endothelial dysfunction and apoptosis. We aimed to explore the role of sphingosine-1-phosphatereceptor 2 (S1PR2) in high glucose-induced endothelial cells apoptosis and to elaborate the underlying mechanism. Human umbilical vein endothelial cells (HUVECs) were cultured in a high glucose with or without S1PR2 antagonist. The apoptosis of the cells was measured by flow cytometry and mitochondrial membrane permeability was detected by the fluorescent probe JC-1...
August 26, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28626422/sphingosine-1-phosphate-receptors-do-they-have-a-therapeutic-potential-in-cardiac-fibrosis
#19
REVIEW
Ambra Vestri, Federica Pierucci, Alessia Frati, Lucia Monaco, Elisabetta Meacci
Sphingosine 1-phosphate (S1P) is a bioactive lipid that is characterized by a peculiar mechanism of action. In fact, S1P, which is produced inside the cell, can act as an intracellular mediator, whereas after its export outside the cell, it can act as ligand of specific G-protein coupled receptors, which were initially named endothelial differentiation gene (Edg) and eventually renamed sphingosine 1-phosphate receptors (S1PRs). Among the five S1PR subtypes, S1PR1, S1PR2 and S1PR3 isoforms show broad tissue gene expression, while S1PR4 is primarily expressed in immune system cells, and S1PR5 is expressed in the central nervous system...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28598085/-inhibitory-effects-of-sphingosine-1-phosphate-receptor-2-on-vascular-permeability-in-mice
#20
Xiao-Wan Li, Xiu-Guo Li, Yoh Takuwa, Hong Cui
OBJECTIVES: To determine the effect of sphingosine-1-phosphate receptor 2 (S1PR2) on vascular permeability in mice. METHODS: Acute lung injury models of mice were constructed with intra-tracheal administration of lipopolysaccharide (LPS) and compared with the controls with intra-tracheal administration of saline. The effect of S1PR2 on vascular permeability was observed by detecting leakage of Evans blue into lung tissues, pulmonary vascular leakage of fluorescein isothiocyanate (FITC)-dextran, and the wet/dry mass ratio of lungs...
September 2016: Sichuan da Xue Xue Bao. Yi Xue Ban, Journal of Sichuan University. Medical Science Edition
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