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https://www.readbyqxmd.com/read/28528469/multiple-sclerosis-treatment-with-fingolimod-profile-of-non-cardiologic-adverse-events
#1
REVIEW
Yara Dadalti Fragoso
Fingolimod was the first oral medication approved for management of multiple sclerosis and is currently used by tens of thousands patients worldwide. Fingolimod acts via the sphingosine 1-phosphate (S1P) receptor, maintaining peripheral lymphocytes entrapped in the lymph nodes. In consequence, there is a reduction in the infiltration of aggressive lymphocytes into the central nervous system. The drug is safe and effective, and its first hours of use are associated with related to S1P receptors in the heart...
May 20, 2017: Acta Neurologica Belgica
https://www.readbyqxmd.com/read/28528321/omega-3-fatty-acids-lipids-and-apoe-lipidation-in-alzheimer-s-disease-a-rationale-for-multi-nutrient-dementia-prevention
#2
Marcus O Grimm, Daniel Michaelson, Tobias Hartmann
In the last decade it has become obvious that Alzheimer's disease (AD) is closely linked to changes in lipids or lipid metabolism. One of the main pathological hallmarks of AD is amyloid-β (Aβ) deposition. Aβ is derived from sequential proteolytic processing of the amyloid precursor protein (APP). Interestingly, both, the APP and all APP secretases are transmembrane proteins which cleave APP close to and in the lipid bilayer. Moreover, apolipoprotein E4 (apoE4) has been identified as the most prevalent genetic risk factor for AD...
May 20, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28524744/sphingosine-1-phosphate-signaling-in-bone-remodeling-multifaceted-roles-and-therapeutic-potential
#3
Anastasia Meshcheryakova, Diana Mechtcheriakova, Peter Pietschmann
Sphingolipids belong to a complex class of lipid molecules that are crucially involved in the regulation of important biological processes including proliferation, migration and apoptosis. Given the significant progress made in understanding the sphingolipid pathobiology of several diseases, sphingolipid-related checkpoints emerge as attractive targets. Recent data indicate the multifaceted contribution of the sphingolipid machinery to osteoclast - osteoblast crosstalk, representing one of the pivotal interactions underlying bone homeostasis...
May 19, 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/28521611/sgpl1-sphingosine-phosphate-lyase-1-modulates-neuronal-autophagy-via-phosphatidylethanolamine-production
#4
Daniel N Mitroi, Indulekha Karunakaran, Markus Gräler, Julie D Saba, Dan Ehninger, María Dolores Ledesma, Gerhild van Echten-Deckert
Macroautophagy/autophagy defects have been identified as critical factors underlying the pathogenesis of neurodegenerative diseases. The roles of the bioactive signaling lipid sphingosine-1-phosphate (S1P) and its catabolic enzyme SGPL1/SPL (sphingosine phosphate lyase 1) in autophagy are increasingly recognized. Here we provide in vitro and in vivo evidence for a previously unidentified route through which SGPL1 modulates autophagy in neurons. SGPL1 cleaves S1P into ethanolamine phosphate, which is directed toward the synthesis of phosphatidylethanolamine (PE) that anchors LC3-I to phagophore membranes in the form of LC3-II...
May 4, 2017: Autophagy
https://www.readbyqxmd.com/read/28521610/sphk1-sphingosine-kinase-1-induces-epithelial-mesenchymal-transition-by-promoting-the-autophagy-linked-lysosomal-degradation-of-cdh1-e-cadherin-in-hepatoma-cells
#5
Hong Liu, Yan Ma, Hong-Wei He, Wu-Li Zhao, Rong-Guang Shao
SPHK1 (sphingosine kinase 1), a regulator of sphingolipid metabolites, plays a causal role in the development of hepatocellular carcinoma (HCC) through augmenting HCC invasion and metastasis. However, the mechanism by which SPHK1 signaling promotes invasion and metastasis in HCC remains to be clarified. Here, we reported that SPHK1 induced the epithelial-mesenchymal transition (EMT) by accelerating CDH1/E-cadherin lysosomal degradation and facilitating the invasion and metastasis of HepG2 cells. Initially, we found that SPHK1 promoted cell migration and invasion and induced the EMT process through decreasing the expression of CDH1, which is an epithelial marker...
May 4, 2017: Autophagy
https://www.readbyqxmd.com/read/28516428/cerebrovascular-angiogenic-reprogramming-upon-lrp1-repression-impact-on-sphingosine-1-phosphate-mediated-signaling-in-brain-endothelial-cell-chemotactism
#6
Amélie Vézina, Cyndia Charfi, Alain Zgheib, Borhane Annabi
Switches in sphingolipid metabolism have recently been associated with oncogenic transformation, and a role for the low-density lipoprotein receptor-related protein 1 (LRP1) in sphingosine-1-phosphate (S1P) proangiogenic signaling inferred. S1P signaling crosstalk with LRP1 in brain microvascular endothelial cells (HBMEC) is however unclear. Transient in vitro siLRP1 gene silencing was compared to stable shLRP1 knockdown. We observed decreased expression of CCAAT/enhancer binding protein β (C/EBPβ), a transcription factor for which multiple binding sites are found within the promoter sequences of all five S1P receptor members, upon stable but not transient LRP1 repression...
May 17, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28515494/ligand-chain-length-drives-activation-of-lipid-g-protein-coupled-receptors
#7
Anastassia Troupiotis-Tsaïlaki, Julian Zachmann, Inés González-Gil, Angel Gonzalez, Silvia Ortega-Gutiérrez, Maria L López-Rodríguez, Leonardo Pardo, Cedric Govaerts
Sphingosine-1-phosphate (S1P) is a lipid mediator that can activate five cell membrane G protein-coupled receptors (GPCRs) which carry a variety of essential functions and are promising drug targets. S1P is composed of a polar zwitterionic head-group and a hydrophobic alkyl chain. This implies an activation mechanism of its cognate receptor that must be significantly different from what is known for prototypical GPCRs (ie receptor to small hydrophilic ligands). Here we aim to identify the structural features responsible for S1P agonism by combining molecular dynamics simulations and functional assays using S1P analogs of different alkyl chain lengths...
May 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28511328/-effects-of-apolipoprotein-e-deficiency-on-sphingosine-1-phosphate-distribution-in-plasma-and-lipoproteins-of-mice
#8
X Q Yang, Y Yu, S D Guo, Y J Cui, G L Hu, L Feng, D X Wang, S C Qin
Objective: To investigate the effects of apolipoprotein E deficiency (Apo E(-/-)) on plasma and lipoprotein distribution of sphingosine-1-phosphate (S1P) in mice. Methods: Five male or female Apo E(-/-) or wild type (WT) mice were fed with chow diet and sacrificed at 32-week-age and plasma was collected. The constituents of lipoprotein(very low density lipoprotein (VLDL), low density lipoprotein (LDL), high density lipoprotein (HDL)) were separated by ultracentrifuge. The protein concentration of constituents was detected by BCA protein quantitative kit, and the S1P concentration in plasma and various lipoprotein constituents was detected by liquid chromatography-tandem mass spectrometry (LC-MS/MS)...
May 24, 2017: Zhonghua Xin Xue Guan Bing za Zhi
https://www.readbyqxmd.com/read/28504963/novel-pleiotropic-effects-of-bioactive-phospholipids-in-human-lung-cancer-metastasis
#9
Gabriela Schneider, Zachariah Payne Sellers, Kamila Bujko, Sham S Kakar, Magda Kucia, Mariusz Z Ratajczak
We previously proposed that one of the unwanted side effects of chemotherapy and radiotherapy is the increase in several peptide- and non-peptide based chemoattractants in damaged tissues, leading to induction of a prometastatic microenvironment for remaining cancer cells. Herein, we turned out our attention to a potential role of bioactive phospholipids (BphsLs), such as sphingosine-1-phosphate (S1P), ceramide-1-phosphate (C1P), lysophosphatidylcholine (LPC), and lysophosphatidic acid (LPA) in lung cancer (LC) metastasis...
April 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28502300/-down-regulation-of-sphingosine-kinase-1-sphk1-enhances-the-chemosensitivity-to-cisplatin-in-human-colon-cancer-rko-cells
#10
Lin Qin, Shiquan Liu, Mengbin Qin, Wenhong Wu, Nan Qin, Zhenhua Fu, Chunyan Xu, Jie'an Huang, Mingyu Lai
Objective To investigate the effect of sphingosine kinase 1 (SphK1) gene silence on the sensitivity to cisplatin (DDP) in RKO colon cancer cell line and the potential mechanism. Methods Targeted SphK1 gene lentivirus virus was constructed to infect RKO cells. The relative mRNA expression of SphK1 was detected by quantitative real-time PCR (qRT-PCR) and the protein level of SphK1 was determined by Western blotting. Then RKO cells were divided into three groups: down-regulated SphK1 group (shSphK1 group), negative control group (shControl group) and blank control group (control group)...
May 2017: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/28500264/s1p1-mediated-anti-ras-cardioprotection-pivotal-role-of-mast-cell-aldh2
#11
Alice Marino, Takuya Sakamoto, Pablo A Robador, Kengo Tomita, Roberto Levi
In the ischemic-reperfused (I/R) heart, renin-containing mast cells (MC) release enzymatically active renin, activating a local renin-angiotensin system (RAS), causing excessive norepinephrine release and arrhythmic dysfunction. Activation of Gi-receptors on MC, and/or ischemic preconditioning (IPC), prevent renin release, thus providing anti-RAS cardioprotection. We questioned whether sphingosine-1-phosphate (S1P), a sphingolipid produced in the I/R heart, might afford anti-RAS cardioprotection by activating Gi-coupled S1P1 receptors (S1P1R) on MC...
May 12, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28499696/fenofibrate-decreases-plasma-ceramide-in-type-2-diabetes-patients-a-novel-marker-of-cvd
#12
M Croyal, Z Kaabia, L León, S Ramin-Mangata, T Baty, F Fall, S Billon-Crossouard, A Aguesse, T Hollstein, D R Sullivan, E Nobecourt, G Lambert, M Krempf
AIM: The benefit of the lipid-lowering drug fenofibrate on cardiovascular outcomes is controversial. Our aim was to find new circulating markers to identify those patients most likely to benefit from fenofibrate prescription. METHODS: Analyses were conducted of plasma samples collected from 102 patients with type 2 diabetes, enrolled in the FIELD trial, before and after fenofibrate treatment (200mg/day). Non-targeted and targeted lipid analyses and apolipoprotein measurements were made using mass spectrometry methods...
May 9, 2017: Diabetes & Metabolism
https://www.readbyqxmd.com/read/28497335/methods-for-analyzing-sphingosine-1-phosphate-signaling-in-human-and-mouse-primary-mast-cells
#13
Alena P Chumanevich, Piper A Wedman, Carole A Oskeritzian
Mast cells produce a potently bioactive sphingolipid metabolite sphingosine-1-phosphate (S1P) constitutively and upon activation. The ligation of S1P to its type 2 receptor on mast cells triggers a novel downstream signaling pathway that we discovered links activation of transcription factor signal transducer and activator of transcription 3 to mast cell-derived chemokine release in both humans and mice. In this chapter, we describe the methods used to study S1P signaling in human and mouse primary mast cells...
May 12, 2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28495476/studies-on-diagnostic-biomarkers-and-therapeutic-mechanism-of-alzheimer-s-disease-through-metabolomics-and-hippocampal-proteomics
#14
Weiwei Lin, Jianmei Zhang, Yanmeng Liu, Ruijun Wu, Haisong Yang, Xiaobo Hu, Xiaomei Ling
Alzheimer's disease (AD) is the main cause of dementia, but precise diagnosis and treatment are not sufficient so far. The purpose of this study is to develop biomarkers and therapeutic targets for diagnosis and better understanding of AD. As a result, lysophosphatidylcholine and intermediates of sphingolipid metabolism including sphinganine-1-phosphate, sphingosine-1-phosphate, sphingomyelin, and sphingosine in plasma were annotated as potential biomarkers by using UPLC-Q-TOF-MS and UHPLC-Q-Exactive-MS. Besides, glutathione S-transferases (GSTs) including GstA3, Gstm1, Gstm5, Gstm3, Gstk1 and Gstp1 were significantly enhanced in AD hippocampus by using label free nano-LC-MS/MS...
May 8, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28494176/comparative-analysis-of-the-effects-of-a-sphingosine-kinase-inhibitor-to-temozolomide-and-radiation-treatment-on-glioblastoma-cell-lines
#15
Liliana R Oancea-Castillo, Carmen Klein, Amir Abdollahi, Klaus-Josef Weber, Anne Régnier-Vigouroux, Ivana Dokic
Glioblastoma multiforme (GBM) exhibits high resistance to the standard treatment of temozolomide (TMZ) combined with radiotherapy, due to its remarkable cell heterogeneity. Accordingly, there is a need to target alternative molecules enhancing specific GBM autocrine or paracrine mechanisms and amplifying the effect of standard treatment. Sphingosine 1-phosphate (S1P) is such a lipid target molecule with an important role in cell invasion and proliferation. Sphingosine kinase inhibitors (SKI) prevent S1P formation and induce increased production of reactive oxygen species (ROS), which may potentiate radiation cytotoxicity...
May 11, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/28494002/involvement-of-band3-in-the-efflux-of-sphingosine-1-phosphate-from-erythrocytes
#16
Makoto Kurano, Masako Nishikawa, Hiroyuki Kuma, Masahiro Jona, Yutaka Yatomi
Sphingosine 1-phosphate (S1P) is a bioactive lipid mediator that is thought to be involved in various diseases. Although the main source of S1P in the plasma is erythrocytes, how S1P is exported from erythrocytes has not been elucidated. When we differentiated K562 cells into erythroblast-like cells with sodium butyrate, we observed that the efflux of S1P was increased without increased expression of previously proposed S1P transporters, while the expression levels of Band3 were increased. Therefore, in this study, we investigated the involvement of Band 3, the most characteristic membranous transporter for erythrocytes, in S1P efflux, using 4,4'-diisothiocyanatodihydrostilbene-2,2'-disulfonic acid, disodium salt (H2DIDS), which is an inhibitor of Band3...
2017: PloS One
https://www.readbyqxmd.com/read/28493876/the-effect-of-sphingosine-1-phosphate-on-colonic-smooth-muscle-contractility-modulation-by-tnbs-induced-colitis
#17
Aishah Al-Jarallah, Mabayoje Oriowo
AIM: Increased levels of circulating sphingosine-1-phosphate (S1P) have been reported in ulcerative colitis. The objective of this study was to examine the effect of S1P on colonic smooth muscle contractility and how is it affected by colitis. METHODS: Colonic inflammation was induced by intrarectal administration of trinitrobenzene sulfonic acid. Five days later colon segments were isolated and used for contractility experiments and immunoblotting. RESULTS: S1P contracted control and inflamed colon segments and the contraction was significantly greater in inflamed colon segments...
2017: PloS One
https://www.readbyqxmd.com/read/28493600/endurance-training-selectively-increases-hdl-bound-sphingosine-1-phosphate-in-the-plasma
#18
Monika Książek, Małgorzata Charmas, Andrzej Klusiewicz, Piotr Zabielski, Barbara Długołęcka, Adrian Chabowski, Marcin Baranowski
Sphingosine-1-phosphate (S1P) is a bioactive lysosphingolipid that is found in relatively high concentration in human plasma. Erythrocytes, endothelial cells, and activated platelets are the main sources of circulating S1P. The majority of plasma S1P is transported bound to high-density lipoprotein (HDL) and albumin. In recent years HDL-bound S1P attracted much attention due to its cardioprotective and anti-atherogenic properties. We have previously found that endurance-trained athletes are characterized by higher plasma S1P concentration compared to untrained individuals...
May 11, 2017: Scandinavian Journal of Medicine & Science in Sports
https://www.readbyqxmd.com/read/28492873/sphingosine-1-phosphate-mediates-fibrosis-in-orbital-fibroblasts-in-graves-orbitopathy
#19
JaeSang Ko, Min Kyoung Chae, Joon H Lee, Eun Jig Lee, Jin Sook Yoon
Purpose: To investigate the effect of sphingosine-1-phosphate (S1P) on fibrosis in orbital fibroblasts in Graves' orbitopathy (GO). Methods: Orbital fibroblasts were cultured from orbital adipose/connective tissues of patients with GO and healthy control subjects. Effects of treatment with TGF-β and cigarette smoke extract (CSE) on S1P receptor (S1PR) messenger RNA (mRNA) and S1P expression were evaluated by real-time polymerase chain reaction and Western blotting...
May 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28489480/ponesimod-a-selective-sphingosine-1-phosphate-s1p1-receptor-modulator-for-autoimmune-diseases-review-of-clinical-pharmacokinetics-and-drug-disposition
#20
Ranjeet Prasad Dash, Rana Rais, Nuggehally R Srinivas
1. Ponesimod, a selective sphingosine 1-phosphate (S1P1) receptor modulator, is undergoing clinical development for the treatment of autoimmune diseases (multiple sclerosis/psoriasis). 2. Published literature data describing pharmacokinetic disposition of ponesimod were collected, reviewed and tabulated. 3. Across various clinical phase I studies, ponesimod displayed consistent pharmacokinetics - relatively faster absorption peak time (approximately 2.5 h), elimination half-life of approximately 30 h, and modest accumulation (2 to 2...
May 10, 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
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