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Sphingosine 1 phosphate

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https://www.readbyqxmd.com/read/29156133/harnessing-sphingosine-1-phosphate-signaling-and-nanotopographical-cues-to-regulate-skeletal-muscle-maturation-and-vascularization
#1
Jonathan Hung Tsui, Kajohnkiart Janebodin, Nicholas Ieronimakis, David Michael Patrick Yama, Hee Seok Yang, Rakchanok Chavanachat, Aislinn L Hays, Haeshin Lee, Morayma Reyes, Deok-Ho Kim
Despite possessing substantial regenerative capacity, skeletal muscle can suffer from loss of function due to catastrophic traumatic injury or degenerative disease. In such cases, engineered tissue grafts hold the potential to restore function and improve patient quality of life. Requirements for successful integration of engineered tissue grafts with the host musculature include cell alignment that mimics host tissue architecture and directional functionality, as well as vascularization to ensure tissue survival...
November 20, 2017: ACS Nano
https://www.readbyqxmd.com/read/29150495/small-dense-high-density-lipoproteins-display-potent-vasorelaxing-activity-reflecting-their-elevated-content-of-sphingosine-1-phosphate
#2
Laurence Persegol, Maryam Darabi, Carolane Dauteuille, Marie Lhomme, Sandrine Chantepie, Kerry-Anne Rye, Patrice Therond, M John Chapman, Robert Salvayre, Anne Negre-Salvayre, Philippe Lesnik, Serge Monier, Anatol Kontush
AIMS: Functional heterogeneity of HDL is attributed to its diverse bioactive components. We evaluated whether vasodilatory effects of HDL differed across HDL subpopulations, reflecting their distinct molecular composition. METHODS: Capacity of five major HDL subfractions to counteract inhibitory effects of oxidized low-density lipoprotein on acetylcholine-induced vasodilation was tested in a rabbit aortic rings model. Nitric oxide (NO) production, an essential pathway in endothelium-dependent vasorelaxation, was studied in SV40-transformed murine endothelial cells (SVEC)...
November 17, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/29149941/pathophysiology-of-septic-shock
#3
REVIEW
James A Russell, Barret Rush, John Boyd
Fundamental features of septic shock are vasodilation, increased permeability, hypovolemia, and ventricular dysfunction. Vasodilation owing to increased nitric oxide and prostaglandins is treated with vasopressors (norepinephrine first). Increased permeability relates to several pathways (Slit/Robo4, vascular endothelial growth factor, angiopoietin 1 and 2/Tie2 pathway, sphingosine-1-phosphate, and heparin-binding protein), some of which are targets for therapies. Hypovolemia is common and crystalloid is recommended for fluid resuscitation...
January 2018: Critical Care Clinics
https://www.readbyqxmd.com/read/29149079/sphingosine-1-phosphate-s1p-signaling-in-glioblastoma-multiforme-a-systematic-review
#4
REVIEW
Shailaja Mahajan-Thakur, Sandra Bien-Möller, Sascha Marx, Henry Schroeder, Bernhard H Rauch
The multifunctional sphingosine-1-phosphate (S1P) is a lipid signaling molecule and central regulator in the development of several cancer types. In recent years, intriguing information has become available regarding the role of S1P in the progression of Glioblastoma multiforme (GBM), the most aggressive and common brain tumor in adults. S1P modulates numerous cellular processes in GBM, such as oncogenesis, proliferation and survival, invasion, migration, metastasis and stem cell behavior. These processes are regulated via a family of five G-protein-coupled S1P receptors (S1PR1-5) and may involve mainly unknown intracellular targets...
November 17, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29147072/paradoxical-association-of-postoperative-plasma-sphingosine-1-phosphate-with-breast-cancer-aggressiveness-and-chemotherapy
#5
Rajesh Ramanathan, Ali Raza, Jamie Sturgill, Debra Lyon, Jessica Young, Nitai C Hait, Kazuaki Takabe
Sphingosine-1-phosphate (S1P) is a bioactive lipid mediator that has been shown to serve an important regulatory function in breast cancer progression. This study analyzes plasma S1P levels in breast cancer patients undergoing adjuvant therapy as compared to healthy control volunteers. 452 plasma S1P samples among 158 breast cancer patients, along with 20 healthy control volunteers, were analyzed. Mean S1P levels did not significantly differ between cancer patients and controls. Smoking was associated with higher S1P levels in cancer patients...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/29147025/sphingolipid-metabolism-in-cancer-signalling-and-therapy
#6
REVIEW
Besim Ogretmen
Sphingolipids, including the two central bioactive lipids ceramide and sphingosine-1-phosphate (S1P), have opposing roles in regulating cancer cell death and survival, respectively, and there have been exciting developments in understanding how sphingolipid metabolism and signalling regulate these processes in response to anticancer therapy. Recent studies have provided mechanistic details of the roles of sphingolipids and their downstream targets in the regulation of tumour growth and response to chemotherapy, radiotherapy and/or immunotherapy using innovative molecular, genetic and pharmacological tools to target sphingolipid signalling nodes in cancer cells...
November 17, 2017: Nature Reviews. Cancer
https://www.readbyqxmd.com/read/29146748/stable-isotope-kinetic-study-of-apom-apolipoprotein-m
#7
Mikaël Croyal, Stéphanie Billon-Crossouard, Sophie Goulitquer, Audrey Aguesse, Luis León, Fanta Fall, Maud Chétiveaux, Thomas Moyon, Valentin Blanchard, Khadija Ouguerram, Gilles Lambert, Estelle Nobécourt, Michel Krempf
OBJECTIVE: ApoM (apolipoprotein M) binds primarily to high-density lipoprotein before to be exchanged with apoB (apolipoprotein B)-containing lipoproteins. Low-density lipoprotein (LDL) receptor-mediated clearance of apoB-containing particles could influence plasma apoM kinetics and decrease its antiatherogenic properties. In humans, we aimed to describe the interaction of apoM kinetics with other components of lipid metabolism to better define its potential benefit on atherosclerosis...
November 16, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29144589/-sphingosine-1-phosphate-immobilized-on-nanotopographical-scaffolds-improve-myogenic-differentiation
#8
Min Suk Lee, Hee Seok Yang
The skeletal muscle consists of highly aligned dense cables of collagen fibers with nanometer feature size to support muscle fibers. The skeletal myocyte can be greatly affected to differentiate by their surrounding topographical structure. To improve myogenic differentiation, we fabricated cell culture platform that sphingosine-1-phosphate (S1P) which regulated myocyte behavior was immobilized on a biomimetic nanopatterned polyurethaneacrylate (PUA) substrate using 3,4-dihydroxyphenylalanine (L-DOPA) for providing topographical and biological cues synergistically...
November 16, 2017: Biotechnology Journal
https://www.readbyqxmd.com/read/29143233/etoposide-upregulates-survival-favoring-sphingosine-1-phosphate-in-etoposide-resistant-retinoblastoma-cells
#9
Vinodh Kakkassery, S Skosyrski, A Lüth, B Kleuser, M van der Giet, R Tate, J Reinhard, A Faissner, S C Joachim, N Kociok
Improved knowledge of retinoblastoma chemotherapy resistance is needed to raise treatment efficiency. The objective of this study was to test whether etoposide alters glucosyl-ceramide, ceramide, sphingosine, and sphingosine-1-phosphate (sphingosine-1-P) levels in parental retinoblastoma cells (WERI Rb1) or their etoposide-resistant subclones (WERI EtoR). WERI Rb1 and WERI EtoR were incubated with 400 ng/ml etoposide for 24 h. Levels of glucosyl-ceramides, ceramides, sphingosine, sphingosine-1-P were detected by Q-TOF mass spectrometry...
November 15, 2017: Pathology Oncology Research: POR
https://www.readbyqxmd.com/read/29140922/fingolimod-reduces-neuropathic-pain-behaviors-in-a-mouse-model-of-multiple-sclerosis-by-a-sphingosine-1-phosphate-receptor-1-dependent-inhibition-of-central-sensitization-in-the-dorsal-horn
#10
Suzanne Doolen, Tommaso Iannitti, Benjamin C Shaw, Carolyn M Grachen, Renee R Donahue, Bradley K Taylor
Multiple sclerosis (MS) is an autoimmune-inflammatory neurodegenerative disease that is often accompanied by a debilitating neuropathic pain. Disease-modifying agents slow the progression of MS and prevent relapses, yet it remains unclear if they yield analgesia. We explored the analgesic potential of fingolimod (FTY720), an agonist/functional antagonist at the sphingosine-1-phosphate receptor 1 (S1PR1), because it reduces hyperalgesia in models of peripheral inflammatory and neuropathic pain. We used a myelin oligodendrocyte glycoprotein 35-55 (MOG35-55) mouse model of experimental autoimmune encephalomyelitis (EAE), modified to avoid frank paralysis and thus allow for assessment of withdrawal behaviors to somatosensory stimuli...
November 13, 2017: Pain
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
#11
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/29138536/spotlight-on-siponimod-and-its-potential-in-the-treatment-of-secondary-progressive-multiple-sclerosis-the-evidence-to-date
#12
REVIEW
Alberto Gajofatto
Siponimod (BAF312) is a synthetic molecule belonging to the sphingosine-1-phosphate (S1P) modulator family, which has putative neuroprotective properties and well-characterized immunomodulating effects mediated by sequestration of B and T cells in secondary lymphoid organs. Compared to fingolimod (ie, precursor of the S1P modulators commercially available for the treatment of relapsing-remitting [RR] multiple sclerosis [MS]), siponimod exhibits selective affinity for types 1 and 5 S1P receptor, leading to a lower risk of adverse events that are mainly induced by S1P3 receptor activation, such as bradycardia and vasoconstriction...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/29137549/the-impact-of-a-long-acting-oral-sphingosine-1-phosphate-analogue-on-ovarian-aging-in-a-rat-model
#13
Sezcan Mumusoglu, Volkan Turan, Hasan Uckan, Aysegul Suzer, Lale Karakoc Sokmensuer, Gurkan Bozdag
In animal studies, intravenous continuous infusion or peritoneal injection of sphingosine-1-phosphate (S1P) has been shown to decrease chemotherapy- and radiotherapy-induced apoptosis on primordial follicles. Although a long-acting oral form of an S1P analogue (FTY720, fingolimod) has been recently developed and utilized in women with multiple sclerosis, there are no data exploring its ability to avoid spontaneous follicle apoptosis. Thirty 10-month-old female rats were randomly assigned to 3 groups to investigate whether fingolimod would be able to decrease the spontaneous ovarian follicle apoptosis ratio...
January 1, 2017: Reproductive Sciences
https://www.readbyqxmd.com/read/29136008/automated-tracking-and-quantification-of-angiogenic-vessel-formation-in-3d-microfluidic-devices
#14
Mengmeng Wang, Lee-Ling Sharon Ong, Justin Dauwels, H Harry Asada
Angiogenesis, the growth of new blood vessels from pre-existing vessels, is a critical step in cancer invasion. Better understanding of the angiogenic mechanisms is required to develop effective antiangiogenic therapies for cancer treatment. We culture angiogenic vessels in 3D microfluidic devices under different Sphingosin-1-phosphate (S1P) conditions and develop an automated vessel formation tracking system (AVFTS) to track the angiogenic vessel formation and extract quantitative vessel information from the experimental time-lapse phase contrast images...
2017: PloS One
https://www.readbyqxmd.com/read/29134505/upregulated-sphingosine-1-phosphate-receptor-1-expression-in-human-and-murine-atherosclerotic-plaques
#15
Hui Liu, Hongjun Jin, Junbin Han, Xuyi Yue, Hao Yang, Mohamed A Zayed, Robert J Gropler, Zhude Tu
PURPOSE: Dysregulation of sphingosine 1-phosphate receptor 1 (S1PR1) signaling contributes to inflammation-related pathophysiological changes in cardiovascular diseases including atherosclerosis (AS). S1PR1-targeting compounds significantly reduce lesion size in murine models of AS. Therefore, characterization of S1PR1 expression in vitro and in vivo in atherosclerotic plaque could enable mechanistic studies and inform S1PR1 targeted therapies. PROCEDURES: H&E staining and immunostaining studies were performed on variably diseased human femoral endarterectomy plaque specimens, as well as mouse aortic sections from ApoE(-/-) mice maintained on a high-fat diet (AS mice)...
November 13, 2017: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
https://www.readbyqxmd.com/read/29133526/involvement-of-g%C3%AE-%C3%AE-subunits-of-gi-protein-coupled-with-s1p-receptor-on-multivesicular-endosomes-in-f-actin-formation-and-cargo-sorting-into-exosomes
#16
Taketoshi Kajimoto, Nesma Nabil Ibrahim Mohamed, Shaymaa Mohamed Mohamed Badawy, Shubi Ambwene Matovelo, Mitsuhiro Hirase, Shunsuke Nakamura, Daisuke Yoshida, Taro Okada, Takeshi Ijuin, Shun-Ichi Nakamura
Exosomes play a critical role in cell-to-cell communication by delivering cargo molecules to recipient cells. However, the mechanism underlying the generation of the exosomal multivesicular endosome (MVE) is one of the mysteries in the field of endosome research. Although sphingolipid metabolites such as ceramide and sphingosine 1-phosphate (S1P) are known to play important roles in MVE formation and maturation, the detailed molecular mechanisms are still unclear. Here, we show that Rho family GTPases, including Cdc42 and Rac1, are constitutively activated on exosomal MVEs and are regulated by S1P signaling as measured by fluorescence resonance energy transfer (FRET)-based conformational changes...
November 13, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29131082/aspirin-inhibits-platelet-derived-sphingosine-1-phosphate-induced-endothelial-cell-migration
#17
Amin Polzin, Betül Knoop, Andreas Böhm, Lisa Dannenberg, Mark Zurek, Tobias Zeus, Malte Kelm, Bodo Levkau, Bernhard H Rauch
BACKGROUND: Aspirin plays a crucial role in the prevention of cardiovascular diseases. We previously described that aspirin has effects beyond inhibition of platelet aggregation, as it inhibited thrombin-mediated release of sphingosine-1-phosphate (S1P) from human platelets. S1P is a bioactive lipid with important functions on inflammation and apoptosis. In endothelial cells (EC), S1P is a key regulator of cell migration. In this study, we aimed to analyze the effects of aspirin on platelet-induced EC migration...
October 31, 2017: Pharmacology
https://www.readbyqxmd.com/read/29130028/sphingosine-kinases-sphingosine-1-phosphate-signaling-in-hepatic-lipid-metabolism
#18
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/29127281/structural-and-functional-insight-of-sphingosine-1-phosphate-mediated-pathogenic-metabolic-reprogramming-in-sickle-cell-disease
#19
Kaiqi Sun, Angelo D'Alessandro, Mostafa H Ahmed, Yujin Zhang, Anren Song, Tzu-Ping Ko, Travis Nemkov, Julie A Reisz, Hongyu Wu, Morayo Adebiyi, Zhangzhe Peng, Jing Gong, Hong Liu, Aji Huang, Yuan Edward Wen, Alexander Q Wen, Vladimir Berka, Mikhail V Bogdanov, Osheiza Abdulmalik, Leng Han, Ah-Lim Tsai, Modupe Idowu, Harinder S Juneja, Rodney E Kellems, William Dowhan, Kirk C Hansen, Martin K Safo, Yang Xia
Elevated sphingosine 1-phosphate (S1P) is detrimental in Sickle Cell Disease (SCD), but the mechanistic basis remains obscure. Here, we report that increased erythrocyte S1P binds to deoxygenated sickle Hb (deoxyHbS), facilitates deoxyHbS anchoring to the membrane, induces release of membrane-bound glycolytic enzymes and in turn switches glucose flux towards glycolysis relative to the pentose phosphate pathway (PPP). Suppressed PPP causes compromised glutathione homeostasis and increased oxidative stress, while enhanced glycolysis induces production of 2,3-bisphosphoglycerate (2,3-BPG) and thus increases deoxyHbS polymerization, sickling, hemolysis and disease progression...
November 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29127024/the-sphingosine-1-phosphate-receptor-modulator-fingolimod-as-a-therapeutic-agent-recent-findings-and-new-perspectives
#20
REVIEW
Andrea Huwiler, Uwe Zangemeister-Wittke
The immunomodulatory drug fingolimod (FTY720, Gilenya(R)) was approved for oral treatment of relapsing-remitting multiple sclerosis, due to its impressive efficacy and good tolerability. Pharmacologically, it acts as an unselective agonist of sphingosine 1-phosphate receptors (S1PR) and as a selective functional antagonist of the S1P1 subtype by induction of receptor downregulation. Since S1P1 is crucial for the regulation of lymphocyte trafficking, its downregulation causes redistribution of the immune cells to secondary lymphoid tissues, resulting in the depletion from the circulation and hence immunosuppression...
November 7, 2017: Pharmacology & Therapeutics
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