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https://www.readbyqxmd.com/read/28646803/effects-of-balneotherapy-on-serum-levels-of-shingosine-1-phosphate-in-patients-with-osteoarthritis
#1
Esra Aycan Ustyol, Fatih Karaarslan, Seldag Bekpinar, Kagan Ozkuk, Nergis Erdogan
Context • Balneotherapy is one of the most commonly used nonpharmacological interventions for osteoarthritis (OA), but its mechanism of action in relieving pain and stiffness and in improving physical function is not well understood. Studies have found that therapy provokes a series of neuroendocrinal reactions with anti-inflammatory and analgesic effects. Sphingosine-1-phosphate (S1P), a bioactive lipid, has been implicated as an important mediator in the maintenance of physiological processes (eg, vascular barrier integrity) and in pathophysiologic processes such as inflammatory conditions...
June 23, 2017: Alternative Therapies in Health and Medicine
https://www.readbyqxmd.com/read/28645614/site-1-protease-a-novel-metabolic-target-for-glioblastoma
#2
Beth T Caruana, Aleksandra Skoric, Andrew J Brown, Louise H Lutze-Mann
Sterol regulatory element binding proteins (SREBPs) are transcriptional regulators of lipids which promote glioblastoma growth. Here, we investigate the effect of inhibiting expression of SREBP target genes in human glioblastoma cells. This was achieved by using PF-429242 to inhibit site-1 protease (S1P), an enzyme required for SREBP activation. Treatment with PF-429242 decreased glioblastoma cell viability, induced apoptosis and downregulated steroid, isoprenoid and unsaturated fatty acid biosynthetic pathways...
June 20, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28642485/sphingosine-1-phosphate-treatment-can-ameliorate-microvascular-leakage-caused-by-combined-alcohol-intoxication-and-hemorrhagic-shock
#3
Travis M Doggett, Natascha G Alves, Sarah Y Yuan, Jerome W Breslin
Fluid resuscitation following hemorrhagic shock is often problematic, with development of prolonged hypotension and edema. In addition, many trauma patients are also intoxicated, which generally worsens outcomes. We directly investigated how alcohol intoxication impacts hemorrhagic shock and resuscitation-induced microvascular leakage using a rat model with intravital microscopic imaging. We also tested the hypothesis that an endothelial barrier-protective bioactive lipid, sphingosine-1-phosphate (S1P), could ameliorate the microvascular leakage following alcohol intoxication plus hemorrhagic shock and resuscitation...
June 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28640982/mechanisms-of-sphingosine-1-phosphate-mediated-vasoconstriction-of-rat-afferent-arterioles
#4
Zhengrong Guan, Fuchenchu Wang, Xiangqin Cui, Edward W Inscho
AIM: Sphingosine-1-phosphate (S1P) influences resistance vessel function and is implicated in renal pathological processes. Previous studies revealed that S1P evoked potent vasoconstriction of the preglomerular microvasculature, but the underlying mechanisms remain incompletely defined. We postulated that S1P-mediated preglomerular microvascular vasoconstriction involves activation of voltage-dependent L-type calcium channels (L-VDCC) and the rho/rho kinase pathway. METHODS: Afferent arteriolar reactivity was assessed in vitro using the blood-perfused rat juxtamedullary nephron preparation and diameter was measured during exposure to physiological and pharmacological agents...
June 22, 2017: Acta Physiologica
https://www.readbyqxmd.com/read/28626422/sphingosine-1-phosphate-receptors-do-they-have-a-therapeutic-potential-in-cardiac-fibrosis
#5
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/28625547/contextual-fear-conditioning-is-enhanced-in-mice-lacking-functional-sphingosine-kinase-2
#6
Mona Lei, Adeena Shafique, Kani Shang, Timothy A Couttas, Hua Zhao, Anthony S Don, Tim Karl
The lipid sphingosine 1-phosphate (S1P) is a potent neuroprotective signalling molecule that signals through its own family of five G-protein coupled receptors. S1P signalling enhances presynaptic glutamate release and is essential for neural development. S1P is synthesized by the enzymes sphingosine kinases 1 and 2 (SphK1 and SphK2), of which SphK2 mRNA and activity is more abundant in the brain. In this study we investigated the consequences of global SphK2 knockout (SphK2(-/-)) on basic motor capabilities, anxiety, learning, and memory in mice, using a range of tests including the elevated plus maze, the cheeseboard, contextual and cued fear conditioning, and fear extinction...
June 15, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28625317/sphingosine-1-phosphate-postconditioning-protects-against-myocardial-ischemia-reperfusion-injury-in-rats-via-mitochondrial-signaling-and-akt-gsk3%C3%AE-phosphorylation
#7
Rui Fang, Lu-Lu Zhang, Li-Zhi Zhang, Wenchang Li, Mengmeng Li, Ke Wen
BACKGROUND AND AIMS: Although preconditioning of sphingosine 1-phosphate (S1P) has been shown to protect myocytes from hypoxia reoxgenation injury in vitro, the role of S1P postconditioning on myocardial ischemia reperfusion injury (MIRI) in vivo and its related mechanism are unknown. The aim of this study was to investigate the protective role of sphingosine 1-phosphate (S1P) postconditioning in MIRI via its effects on mitochondrial signaling and Akt/Gsk3β phosphorylation. METHODS: Rats were subjected to MIRI, consisting of 30 min of ischemia followed by 120 min of reperfusion, with S1P administered at the beginning of the reperfusion...
February 2017: Archives of Medical Research
https://www.readbyqxmd.com/read/28623546/targeting-sphingosine-1-phosphate-signaling-for-cancer-therapy
#8
REVIEW
Zuoquan Xie, Hong Liu, Meiyu Geng
Sphingosine-1-phosphate (S1P) is a potent pleotropic bioactive lipid mediator involved in immune cell trafficking, cell survival, cell proliferation, cell migration, angiogenesis and many other cellular processes. S1P either activates S1P receptors (S1PR1-5) through "inside-out signaling" or acts directly on intracellular targets to regulate various cellular processes. In the past two decades, much progress has been made in exploring S1P signaling and its pathogenic roles in diseases as well as in developing modulators of S1P signaling, including S1P agonists, S1P antagonists and sphingosine kinase (SphK) inhibitors...
May 27, 2017: Science China. Life Sciences
https://www.readbyqxmd.com/read/28620801/fty720-attenuates-infection-induced-enhancement-of-a%C3%AE-accumulation-in-app-ps1-mice-by-modulating-astrocytic-activation
#9
Róisín M McManus, Orla M Finucane, Mieszko M Wilk, Kingston H G Mills, Marina A Lynch
It is well established that infection has a significant detrimental effect on patients with Alzheimer's disease (AD), accelerating cognitive decline and, even in healthy ageing individuals, increasing amyloid-β (Aβ) accumulation in the brain. In animal models of AD infection can also cause damage, with evidence of increased neuroinflammation, amyloid pathology and deterioration of cognitive function. These changes are against a backdrop of an age- and AD-related increase in susceptibility to infection. Here we set out to determine whether FTY720, a molecule that binds sphingosine-1-phosphate (S1P) receptors and with known immunosuppressant effects mediating its therapeutic action in multiple sclerosis (MS), might modulate the impact of infection in a mouse model of AD...
June 15, 2017: Journal of Neuroimmune Pharmacology: the Official Journal of the Society on NeuroImmune Pharmacology
https://www.readbyqxmd.com/read/28618839/sphingosine-kinase-and-sphingosine-1-phosphate-in-liver-pathobiology
#10
Timothy Rohrbach, Michael Maceyka, Sarah Spiegel
Over 20 years ago, sphingosine-1-phosphate (S1P) was discovered to be a bioactive signaling molecule. Subsequent studies later identified two related kinases, sphingosine kinase 1 and 2, which are responsible for the phosphorylation of sphingosine to S1P. Many stimuli increase sphingosine kinase activity and S1P production and secretion. Outside the cell, S1P can bind to and activate five S1P-specific G protein-coupled receptors (S1PR1-5) to regulate many important cellular and physiological processes in an autocrine or paracrine manner...
June 15, 2017: Critical Reviews in Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28609704/sphingosine-1-phosphate-s1p-suppresses-the-collagen-induced-activation-of-human-platelets-via-s1p4-receptor
#11
Takashi Onuma, Kumiko Tanabe, Yuko Kito, Masanori Tsujimoto, Kodai Uematsu, Yukiko Enomoto, Rie Matsushima-Nishiwaki, Tomoaki Doi, Kiyoshi Nagase, Shigeru Akamatsu, Haruhiko Tokuda, Shinji Ogura, Toru Iwama, Osamu Kozawa, Hiroki Iida
Sphingosine 1-phosphate (S1P) is as an extracellular factor that acts as a potent lipid mediator by binding to specific receptors, S1P receptors (S1PRs). However, the precise role of S1P in human platelets that express S1PRs has not yet been fully clarified. We previously reported that heat shock protein 27 (HSP27) is released from human platelets accompanied by its phosphorylation stimulated by collagen. In the present study, we investigated the effect of S1P on the collagen-induced platelet activation. S1P pretreatment markedly attenuated the collagen-induced aggregation...
June 2, 2017: Thrombosis Research
https://www.readbyqxmd.com/read/28607130/s1pr1-sphingosine-1-phosphate-receptor-1-signaling-regulates-blood-flow-and-pressure
#12
Anna Cantalupo, Antonella Gargiulo, Elona Dautaj, Catherine Liu, Yi Zhang, Timothy Hla, Annarita Di Lorenzo
Nitric oxide is one of the major endothelial-derived vasoactive factors that regulate blood pressure (BP), and the bioactive lipid mediator S1P (sphingosine-1-phosphate) is a potent activator of endothelial nitric oxide synthase through G protein-coupled receptors. Endothelial-derived S1P and the autocrine/paracrine activation of S1PR (S1P receptors) play an important role in preserving vascular functions and BP homeostasis. Furthermore, FTY720 (fingolimod), binding to 4 out of 5 S1PRs recently approved by the Food and Drug Administration to treat autoimmune conditions, induces a modest and transient decrease in heart rate in both animals and humans, suggesting that drugs targeting sphingolipid signaling affect cardiovascular functions in vivo...
June 12, 2017: Hypertension
https://www.readbyqxmd.com/read/28605810/a-compact-whole-eye-perfusion-system-to-evaluate-pharmacologic-responses-of-outflow-facility
#13
Enhua H Zhou, Michael Paolucci, Thaddeus P Dryja, Ted Manley, Chuanxi Xiang, Dennis S Rice, Ganesh Prasanna, Amy Chen
Purpose: To discover novel therapies that lower IOP by increasing aqueous humor outflow facility, ex vivo ocular perfusion systems provide a valuable tool. However, currently available designs are limited by their throughput. Here we report the development of a compact, scalable perfusion system with improved throughput and its validation using bovine and porcine eyes. Methods: At a fixed IOP of 6 mm Hg, flow rate was measured by flow sensors. We validated the system by measuring the outflow responses to Y-39983 (a Rho kinase inhibitor), endothelin-1 (ET-1), ambrisentan (an antagonist for endothelin receptor A [ETA]), sphigosine-1-phosphate (S1P), JTE-013 (antagonist for S1P receptor 2 [S1P2]), S-nitroso-N-acetylpenicillamine (SNAP, a nitric oxide [NO] donor), and 3-Morpholino-sydnonimine (SIN-1, another NO donor)...
June 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28600291/sphingosine-1-phosphate-lyase-enhances-the-activation-of-ikk%C3%AE%C2%B5-to-promote-type-i-ifn-mediated-innate-immune-responses-to-influenza-a-virus-infection
#14
Madhuvanthi Vijayan, Chuan Xia, Yul Eum Song, Hanh Ngo, Caleb J Studstill, Kelly Drews, Todd E Fox, Marc C Johnson, John Hiscott, Mark Kester, Stephen Alexander, Bumsuk Hahm
Sphingosine 1-phosphate (S1P) lyase (SPL) is an intracellular enzyme that mediates the irreversible degradation of the bioactive lipid S1P. We have previously reported that overexpressed SPL displays anti-influenza viral activity; however, the underlying mechanism is incompletely understood. In this study, we demonstrate that SPL functions as a positive regulator of IKKε to propel type I IFN-mediated innate immune responses against viral infection. Exogenous SPL expression inhibited influenza A virus replication, which correlated with an increase in type I IFN production and IFN-stimulated gene accumulation upon infection...
June 9, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28599970/cerebral-near-infrared-spectroscopy-insensitively-detects-low-cerebral-venous-oxygen-saturations-after-stage-1-palliation
#15
Erin Rescoe, Xiaoqi Tang, Dorothy Alison Perry, Lynn A Sleeper, James A DiNardo, Barry D Kussman, John N Kheir
BACKGROUND: Measurement of cerebral venous oxyhemoglobin saturation (ScvO2) is considered a gold standard in assessing the adequacy of tissue oxygen delivery (DO2) after the stage 1 palliation (S1P), with SvO2 <30% often representing severely compromised DO2. Regional oxygenation index (rSO2) based on near-infrared resonance spectroscopy (NIRS) frequently is used to screen for compromised DO2, although its sensitivity to detect severe abnormalities in SvO2 is uncertain. METHODS: ScvO2 was measured by co-oximetry from the internal jugular vein as clinically indicated in 73 neonates after S1P...
May 16, 2017: Journal of Thoracic and Cardiovascular Surgery
https://www.readbyqxmd.com/read/28596734/characterization-and-expression-of-sphingosine-1-phosphate-receptors-in-human-and-rat-heart
#16
Naseer Ahmed, Daniele Linardi, Ilaria Decimo, Riffat Mehboob, Mebratu A Gebrie, Giulio Innamorati, Giovanni B Luciani, Giuseppe Faggian, Alessio Rungatscher
Aim: Sphingosine 1-phosphate (S1P), sphingolipid derivatives are known anti-inflammatory, anti-apoptotic, and anti-oxidant agent. S1P have been demonstrated to have a role in the cardiovascular system. The purpose of this study was to understand the precise expression and distribution of S1P receptors (S1PRs) in human and rat cardiovascular tissues to know the significance and possible implementation of our experimental studies in rat models. Methods and Results: In this study, we investigated the localization of S1PRs in human heart samples from cardiac surgery department, University of Verona Hospital and rat samples...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28588581/role-of-sphingosine-1-phosphate-in-mast-cell-functions-and-asthma-and-its-regulation-by-non-coding-rna
#17
REVIEW
Rohit Saluja, Ashok Kumar, Manju Jain, Sudhir K Goel, Aklank Jain
Sphingolipid metabolites are emerging as important signaling molecules in allergic diseases specifically asthma. One of the sphingolipid metabolite, sphingosine-1-phosphate (S1P), is involved in cell differentiation, proliferation, survival, migration, and angiogenesis. In the allergic diseases, alteration of S1P levels influences the differentiation and responsiveness of mast cells (MCs). S1P is synthesized by two sphingosine kinases (SphKs), sphingosine kinase 1, and sphingosine kinase 2. Engagement of IgE to the FcεRI receptor induces the activation of both the SphKs and generates S1P...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28588048/the-sphingosine-1-phosphate-break-down-product-2e-hexadecenal-forms-protein-adducts-and-glutathione-conjugates-in-vitro
#18
Fabian Schumacher, Corinna Neuber, Hannah Finke, Kai Nieschalke, Jessica Baesler, Erich Gulbins, Burkhard Kleuser
Sphingosine 1-phosphate (S1P), a bioactive lipid involved in various physiological processes such as cell proliferation and apoptosis, can be irreversibly cleaved by the S1P lyase, yielding phosphoethanolamine and (2E)-hexadecenal (2EHD). The latter metabolite, an α,β-unsaturated fatty aldehyde, may be susceptible to nucleophilic attack by cellular biomolecules. Hence, we studied whether 2EHD forms reaction products with glutathione (GSH) and proteins in vitro Using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and stable isotopically labeled reference material, we identified a total of nine novel reaction products of 2EHD in a cell-free approach: two GSH conjugates and seven L-amino acid adducts...
June 6, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28587987/sphingosine-kinase-1-sk1-allosteric-inhibitors-that-target-the-dimerization-site
#19
Ozge Bayraktar, Elif Ozkirimli, Kutlu Ulgen
The sphingosine kinase 1 (SK1)/sphingosine-1-phosphate (S1P) signaling pathway is a crucial target for numerous human diseases from cancer to cardiovascular diseases. However, available SK1 inhibitors that target the active site suffer from poor potency, selectivity and pharmacokinetic properties. The selectivity issue of the kinases, which share a highly-conserved ATP-pocket, can be overcome by targeting the less-conserved allosteric sites. SK1 is known to function minimally as a dimer; however, the crystal structure of the SK1 dimer has not been determined...
May 29, 2017: Computational Biology and Chemistry
https://www.readbyqxmd.com/read/28577576/sphingosine-1-phosphate-receptor-3-and-rhoa-signaling-mediate-inflammatory-gene-expression-in-astrocytes
#20
Stephanie S Dusaban, Jerold Chun, Hugh Rosen, Nicole H Purcell, Joan Heller Brown
BACKGROUND: Sphingosine 1-phosphate (S1P) signals through G protein-coupled receptors to elicit a wide range of cellular responses. In CNS injury and disease, the blood-brain barrier is compromised, causing leakage of S1P from blood into the brain. S1P can also be locally generated through the enzyme sphingosine kinase-1 (Sphk1). Our previous studies demonstrated that S1P activates inflammation in murine astrocytes. The S1P1 receptor subtype has been most associated with CNS disease, particularly multiple sclerosis...
June 2, 2017: Journal of Neuroinflammation
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