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Sphingosine 1 phosphate

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https://www.readbyqxmd.com/read/28812220/sphingosine-1-phosphate-receptor-modulators-for-the-treatment-of-multiple-sclerosis
#1
REVIEW
Burhan Z Chaudhry, Jeffrey A Cohen, Devon S Conway
Sphingosine 1-phosphate receptor (S1PR) modulators possess a unique mechanism of action in the treatment of multiple sclerosis (MS). Subtype 1 of the S1PR is expressed on the surface of lymphocytes and is important in regulating egression from lymph nodes. The S1PR modulators indirectly antagonize the receptor's function leading to sequestration of lymphocytes in the lymph nodes. Fingolimod was the first S1PR modulator to receive regulatory approval for relapsing-remitting MS after 2 phase III trials demonstrated potent efficacy, safety, and tolerability...
August 15, 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/28811382/an-engineered-s1p-chaperone-attenuates-hypertension-and-ischemic-injury
#2
Steven L Swendeman, Yuquan Xiong, Anna Cantalupo, Hui Yuan, Nathalie Burg, Yu Hisano, Andreane Cartier, Catherine H Liu, Eric Engelbrecht, Victoria Blaho, Yi Zhang, Keisuke Yanagida, Sylvain Galvani, Hideru Obinata, Jane E Salmon, Teresa Sanchez, Annarita Di Lorenzo, Timothy Hla
Endothelial dysfunction, a hallmark of vascular disease, is restored by plasma high-density lipoprotein (HDL). However, a generalized increase in HDL abundance is not beneficial, suggesting that specific HDL species mediate protective effects. Apolipoprotein M-containing HDL (ApoM(+)HDL), which carries the bioactive lipid sphingosine 1-phosphate (S1P), promotes endothelial function by activating G protein-coupled S1P receptors. Moreover, HDL-bound S1P is limiting in several inflammatory, metabolic, and vascular diseases...
August 15, 2017: Science Signaling
https://www.readbyqxmd.com/read/28806736/unravelling-the-interplay-of-sphingolipids-and-tgf-%C3%AE-signaling-in-the-human-corneal-stroma
#3
Sarah E Nicholas, Tyler G Rowsey, Shrestha Priyadarsini, Nawajes A Mandal, Dimitrios Karamichos
PURPOSE: To delineate the role of Sphingolipids (SPLs) in the human cornea and their cross-talks with transforming growth factor beta (TGF-β) in order to develop novel, non-invasive therapies. METHODS: Human corneal fibroblasts (HCFs) were harvested from healthy donors, stimulated with Vitamin C to promote extracellular matrix assembly, treated with exogenous sphingosine-1-phosphate (S1P) or sphingosine kinase inhibitor 2 (SPHK I2) and isolated after 4 weeks for further analysis...
2017: PloS One
https://www.readbyqxmd.com/read/28804221/s1p-provokes-tumor-lymphangiogenesis-via-macrophage-derived-mediators-such-as-il-1%C3%AE-or-lipocalin-2
#4
REVIEW
Shahzad N Syed, Michaela Jung, Andreas Weigert, Bernhard Brüne
A pleiotropic signaling lipid, sphingosine-1-phosphate (S1P), has been implicated in various pathophysiological processes supporting tumor growth and metastasis. However, there are only a few descriptive studies suggesting a role of S1P in tumor lymphangiogenesis, which is critical for tumor growth and dissemination. Corroborating own data, the literature suggests that apoptotic tumor cell-derived S1P alters the phenotype of tumor-associated macrophages (TAMs) to gain protumor functions. However, mechanistically, the role of TAM-induced lymphangiogenesis has only been poorly described, mostly linked to the production of lymphangiogenic factors such as vascular endothelial growth factor C (VEGF-C) and VEGF-D, or transdifferentiation into lymphatic endothelial cells...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28794483/impaired-lymphocyte-trafficking-in-mice-deficient-in-the-kinase-activity-of-pkn1
#5
Rana Mashud, Akira Nomachi, Akihide Hayakawa, Koji Kubouchi, Sally Danno, Takako Hirata, Kazuhiko Matsuo, Takashi Nakayama, Ryosuke Satoh, Reiko Sugiura, Manabu Abe, Kenji Sakimura, Shigeharu Wakana, Hiroyuki Ohsaki, Shingo Kamoshida, Hideyuki Mukai
Knock-in mice lacking PKN1 kinase activity were generated by introducing a T778A point mutation in the catalytic domain. PKN1[T778A] mutant mice developed to adulthood without apparent external abnormalities, but exhibited lower T and B lymphocyte counts in the peripheral blood than those of wild-type (WT) mice. T and B cell development proceeded in an apparently normal fashion in bone marrow and thymus of PKN1[T778A] mice, however, the number of T and B cell counts were significantly higher in the lymph nodes and spleen of mutant mice in those of WT mice...
August 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28789830/sphingosine-kinase-1-a-potential-therapeutic-target-in-pulmonary-arterial-hypertension
#6
REVIEW
Nigel J Pyne, Susan Pyne
Sphingosine kinase 1 (SphK1) knockout mice are protected against pulmonary hypertension and expression levels of the enzyme are increased in the lungs of pulmonary arterial hypertensive (PAH) patients. Moreover, sphingosine 1-phosphate can promote vascular remodeling/vasoconstriction in rodent and human pulmonary arterial smooth muscle cell models. Therefore, SphK1 might be a novel target for treatment of PAH. However, in our opinion, more refined strategies to target SphK1 are needed because this enzyme is protective against endothelial dysfunction and can become resistant to SphK1 inhibitors in vascular smooth muscle, thereby potentially limiting their effectiveness in PAH...
August 5, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28783871/cardiac-safety-of-ozanimod-a-novel-sphingosine-1-phosphate-receptor-modulator-results-of-a-thorough-qt-qtc-study
#7
Jonathan Q Tran, Jeffrey P Hartung, Allan D Olson, Boaz Mendzelevski, Gregg A Timony, Marcus F Boehm, Robert J Peach, Sheila Gujrathi, Paul A Frohna
Ozanimod is a novel, selective, oral sphingosine-1-phosphate (1 and 5) receptor modulator in development for multiple sclerosis and inflammatory bowel disease. This randomized, double-blind, placebo-controlled, positive-controlled, parallel-group thorough QT study characterized the effects of ozanimod on cardiac repolarization in healthy subjects. Eligible subjects were randomized to 1 of 2 groups: ozanimod (escalated from 0.25 to 2 mg over 14 days) or placebo (for 14 days). A single dose of moxifloxacin 400 mg or placebo was administered on days 2 and 17...
August 7, 2017: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/28775072/lmo2-lim-domain-only-2-modulates-sphk1-sphingosine-kinase-and-promotes-endothelial-cell-migration
#8
Gianfranco Matrone, Shu Meng, Qilin Gu, Jie Lv, Longhou Fang, Kaifu Chen, John P Cooke
OBJECTIVE: Lmo (LIM-domain-only)2 transcription factor is involved in hematopoiesis and vascular remodeling. Sphk (sphingosine kinase)1 phosphorylates sphingosine to S1P (sphingosine-1-phosphate). We hypothesized that Lmo2 regulates Sphk1 to promote endothelial cell (EC) migration and vascular development. APPROACH AND RESULTS: Lmo2 and Sphk1 knockdown (KD) were performed in Tg(fli1:EGFP) (y1) zebra fish and in human umbilical vein EC. Rescue of phenotypes or overexpression of these factors were achieved using mRNA encoding Lmo2 or Sphk1...
August 3, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28771545/augmented-sphingosine-1-phosphate-receptor-1-signaling-in-cardiac-fibroblasts-induces-cardiac-hypertrophy-and-fibrosis-through-angiotensin-ii-and-interleukin-6
#9
Sei-Ichiro Ohkura, Soichiro Usui, Shin-Ichiro Takashima, Noriko Takuwa, Kazuaki Yoshioka, Yasuo Okamoto, Yutaka Inagaki, Naotoshi Sugimoto, Teppei Kitano, Masayuki Takamura, Takashi Wada, Shuichi Kaneko, Yoh Takuwa
Cardiac fibroblasts, together with cardiomyocytes, occupy the majority of cells in the myocardium and are involved in myocardial remodeling. The lysophospholipid mediator sphigosine-1-phosphate (S1P) regulates functions of cardiovascular cells through multiple receptors including S1PR1-S1PR3. S1PR1 but not other S1P receptors was upregulated in angiotensin II-induced hypertrophic hearts. Therefore, we investigated a role of S1PR1 in fibroblasts for cardiac remodeling by employing transgenic mice that overexpressed S1PR1 under the control of α-smooth muscle actin promoter...
2017: PloS One
https://www.readbyqxmd.com/read/28770493/measurement-of-lysophosphatidic-acid-and-sphingosine-1-phosphate-by-liquid-chromatography-coupled-electrospray-ionization-tandem-mass-spectrometry
#10
Maria P Kraemer, Suchismita Halder, Susan S Smyth, Andrew J Morris
Lysophosphatidic acids and sphingosine-1-phosphate are bioactive lipids that regulate diverse cellular and physiological processes through actions that are largely mediated by cell surface receptors. The roles played by these lipids in multiple disease processes make the enzymes and receptors involved in their synthesis, inactivation, and signaling attractive targets for pharmacological therapies. In this chapter we describe methods for sensitive accurate quantitation of LPA and S1P levels in biological fluids using liquid chromatography-coupled electrospray ionization tandem mass spectrometry...
August 3, 2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28767388/mobilization-studies-in-mice-deficient-in-sphingosine-kinase-2-support-a-crucial-role-of-the-plasma-level-of-sphingosine-1-phosphate-in-the-egress-of-hematopoietic-stem-progenitor-cells
#11
Mateusz Adamiak, Lakshman Chelvarajan, Kevin R Lynch, Webster L Santos, Ahmed Abdel-Latif, Mariusz Z Ratajczak
Sphingosine-1-phosphate (S1P) is a bioactive lipid involved in cell signaling and, if released from cells, also plays a crucial role in regulating the trafficking of lympho-hematopoietic cells, including primitive hematopoietic stem/progenitor cells (HSPCs). It has been demonstrated that S1P chemoattracts HSPCs, and its level in peripheral blood creates a gradient directing egress of these cells during mobilization. In this paper we analyzed hematopoiesis in mice deficient in sphingosine kinase 2 (Sphk2-KO mice) and studied the effect of this mutation on plasma S1P levels...
July 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28765947/acid-ceramidase-confers-radioresistance-to-glioblastoma-cells
#12
Ninh B Doan, Ha S Nguyen, Mona M Al-Gizawiy, Wade M Mueller, Roger A Sabbadini, Scott D Rand, Jennifer M Connelly, Christopher R Chitambar, Kathleen M Schmainda, Shama P Mirza
Glioblastoma multiforme (GBM) is the most common primary, intracranial malignancy of the central nervous system. The standard treatment protocol, which involves surgical resection, and concurrent radiation with adjuvant temozolomide (TMZ), still imparts a grim prognosis. Ultimately, all GBMs exhibit recurrence or progression, developing resistance to standard treatment. This study demonstrates that GBMs acquire resistance to radiation via upregulation of acid ceramidase (ASAH1) and sphingosine‑1-phosphate (Sph-1P)...
July 28, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28765121/novel-therapies-for-immune-mediated-inflammatory-diseases-what-can-we-learn-from-their-use-in-rheumatoid-arthritis-spondyloarthritis-systemic-lupus-erythematosus-psoriasis-crohn-s-disease-and-ulcerative-colitis
#13
REVIEW
Kenneth F Baker, John D Isaacs
The past three decades have witnessed remarkable advances in our ability to target specific elements of the immune and inflammatory response, fuelled by advances in both biotechnology and disease knowledge. As well as providing superior treatments for immune-mediated inflammatory diseases (IMIDs), such therapies also offer unrivalled opportunities to study the underlying immunopathological basis of these conditions.In this review, we explore recent approaches to the treatment of IMIDs and the insights to pathobiology that they provide...
August 1, 2017: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/28758826/implication-of-sphingosine-1-phosphate-signaling-in-diseases-molecular-mechanism-and-therapeutic-strategies
#14
Mohd Arish, Mohammed Alaidarous, Rahat Ali, Yusuf Akhter, Abdur Rub
Sphingosine-1-phosphate signaling is emerging as a critical regulator of cellular processes that is initiated by the intracellular production of bioactive lipid molecule, sphingosine-1-phosphate. Binding of sphingosine-1-phosphate to its extracellular receptors activates diverse downstream signaling that play a critical role in governing physiological processes. Increasing evidence suggests that this signaling pathway often gets impaired during pathophysiological and diseased conditions and hence manipulation of this signaling pathway may be beneficial in providing treatment...
October 2017: Journal of Receptor and Signal Transduction Research
https://www.readbyqxmd.com/read/28758149/adiponectin-and-its-hydrolase-activated-receptors
#15
Ankit X Sharma, William L Holland
The relevance of adiponectin to insulin sensitivity has been elucidated over the last two decades. As a promoter of ceramide degradation, it works through its cognate receptors, AdipoR1 and AdipoR2, to alter bioactive sphingolipid species. Adiponectin diminishes the accumulation of ceramide, a lipid metabolite which can play a causal role in obesity-induced insulin resistance. Concurrently, adiponectin stimulates the production of sphingosine-1-phosphate (S1P), a cyto-protective molecule that accentuates adiponectin's positive metabolic effects...
June 2017: Journal of Nature and Science
https://www.readbyqxmd.com/read/28755279/in-vitro-methods-to-study-the-modulation-of-migration-and-invasion-by-sphingosine-1-phosphate
#16
Melina G Castro, Ludmila E Campos, Yamila I Rodriguez, Sergio E Alvarez
Sphingosine-1-phosphate (S1P) is a bioactive lipid that modulates migratory behavior of cells during embryonic development. In addition, S1P might promote tumor progression by enhancing migratory ability and invasiveness of tumor cells. Migration is a complex process that implies cytoskeletal reorganization and formation of structures that enable cell movement. Besides having similar requirements than migration, invasion also involves proteolytic degradation of extracellular matrix (ECM). Matrix metalloproteases (MMPs) have been identified to break down components of the ECM, allowing cancer cells to spread out of the primary tumor...
July 29, 2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28752787/the-xenopus-tadpole-an-in-vivo-model-to-screen-drugs-favoring-remyelination
#17
Abdelkrim Mannioui, Quentin Vauzanges, Jean Baptiste Fini, Esther Henriet, Somya Sekizar, Loris Azoyan, Jean Léon Thomas, David Du Pasquier, Carine Giovannangeli, Barbara Demeneix, Catherine Lubetzki, Bernard Zalc
BACKGROUND: In multiple sclerosis, development of screening tools for remyelination-promoting molecules is timely. OBJECTIVE: A Xenopus transgenic line allowing conditional ablation of myelinating oligodendrocytes has been adapted for in vivo screening of remyelination-favoring molecules. METHODS: In this transgenic, the green fluorescent protein reporter is fused to E. coli nitroreductase and expressed specifically in myelinating oligodendrocytes...
July 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/28749426/a-novel-perspective-on-the-apom-s1p-axis-highlighting-the-metabolism-of-apom-and-its-role-in-liver-fibrosis-and-neuroinflammation
#18
REVIEW
Stefan Hajny, Christina Christoffersen
Hepatocytes, renal proximal tubule cells as well as the highly specialized endothelium of the blood brain barrier (BBB) express and secrete apolipoprotein M (apoM). ApoM is a typical lipocalin containing a hydrophobic binding pocket predominantly carrying Sphingosine-1-Phosphate (S1P). The small signaling molecule S1P is associated with several physiological as well as pathological pathways whereas the role of apoM is less explored. Hepatic apoM acts as a chaperone to transport S1P through the circulation and kidney derived apoM seems to play a role in S1P recovery to prevent urinal loss...
July 27, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28745324/a-committed-postselection-precursor-to-natural-tcr%C3%AE-%C3%AE-intraepithelial-lymphocytes
#19
Christoph S N Klose, Jonas F Hummel, Lena Faller, Yannick d'Hargues, Karolina Ebert, Yakup Tanriver
The intestine is a major immune organ with several specialized lymphoid structures and immune cells. Among these are thymus-derived natural intraepithelial lymphocytes (IELs) that lack expression of the classical co-receptors CD4 or CD8αβ (double negative (DN)). Natural IELs are both αβ(+) and γδ(+) T cells that play important roles in the maintenance of the epithelial barrier at steady state and during inflammation. The transcription factor T-bet is essential for the peripheral development of natural IELs, but its role during thymic development has remained less clear...
July 26, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28742634/fingolimod-fty-720-is-capable-of-reversing-tumor-necrosis-factor-induced-decreases-in-cochlear-blood-flow
#20
Mattis Bertlich, Friedrich Ihler, Bernhard G Weiss, Saskia Freytag, Mark Jakob, Michael Strupp, Hannah Pellkofer, Martin Canis
HYPOTHESIS: The potential of Fingolimod (FTY-720), a sphingosine-1-phosphate analogue, to revoke the changes in cochlear blood flow induced by tumor necrosis factor (TNF) was investigated. BACKGROUND: Impairment of cochlear blood flow has often been considered as the common final pathway of various inner ear pathologies. TNF, an ubiquitous cytokine, plays a major role in these pathologies, reducing cochlear blood flow via sphingosine-1-phosphate-signaling. METHODS: Fifteen Dunkin-Hartley guinea pigs were randomly assigned to one of three groups (placebo/placebo, TNF/placebo, TNF/FTY-720)...
September 2017: Otology & Neurotology
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