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Sphingosine-1-phosphate

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https://www.readbyqxmd.com/read/28324485/maintenance-of-human-embryonic-stem-cells-by-sphingosine-1-phosphate-and-platelet-derived-growth-factor
#1
Raymond C B Wong, Martin F Pera, Alice Pébay
Human embryonic stem cells (hESCs) have historically been cultivated on feeder layers of primary mouse embryonic fibroblasts (MEF) in a medium supplemented with fetal calf serum (FCS). However, serum contains a wide variety of biologically active compounds that might adversely affect hESC growth and differentiation. Thus, cultivation of stem cells in FCS complicates experimental approaches to define the intracellular mechanisms required for hESC maintenance. This chapter describes the serum-free maintenance of hESCs in culture by addition of sphingosine-1-phosphate (S1P) and platelet-derived growth factor (PDGF)...
March 22, 2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28315304/sphingosine-1-phosphate-a-double-edged-sword-in-the-brain
#2
REVIEW
Indulekha Karunakaran, Gerhild van Echten-Deckert
The physiological functions of sphingosine 1-phosphate (S1P) and its pathological roles in various diseases are increasingly being elucidated. Particularly, a growing body of literature has implicated S1P in the pathogenesis of brain related disorders. With the deciphering of more intricate aspects of S1P signalling, there is also a need to reconsider the notion of S1P only as a determinant of cell survival and proliferation. Further the concept of 'S1P-ceramide' balance as the controlling switch of cellular fate and functions needs to be refined...
March 14, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28314215/a-metabolomic-approach-shows-sphingosine-1-phosphate-and-lysophospholipids-as-mediators-of-the-therapeutic-effect-of-liver-growth-factor-in-emphysema
#3
A Navarrete, F J Rupérez, T O Mendes, S Pérez-Rial, A Girón-Martínez, R Terrón-Expósito, J J Díaz-Gil, G Peces-Barba, C Barbas, A García
Tobacco smoke exposure is the principal cause of lung tissue destruction, which in turn results in emphysema that leads into shortness of breath. Liver growth factor (LGF, a cell and tissue regenerating factor with therapeutic activity in several organs) has antifibrotic and antioxidant properties that could be useful to promote lung tissue regenerating capacity in damaged lungs. The current study has examined differences in metabolite profiles (fingerprints) of plasma from mice (strain C57BL/6J, susceptible to develop emphysema) exposed to tobacco smoke during six months...
February 27, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28302566/mechanisms-of-sphingosine-1-phosphate-receptor-signalling-in-cancer
#4
REVIEW
Sathya Narayanan Patmanathan, Wei Wang, Lee Fah Yap, Deron R Herr, Ian C Paterson
S1P is a small bioactive lipid which exerts its effects following binding to a family of five G protein-coupled receptors, known as S1P1-5. Following receptor activation, multiple signalling cascades are activated, allowing S1P to regulate a range of cellular processes, such as proliferation, apoptosis, migration and angiogenesis. There is strong evidence implicating the involvement of S1P receptors (S1PRs) in cancer progression and the oncogenic effects of S1P can result from alterations in the expression of one or more of the S1PRs and/or the enzymes that regulate the levels of S1P...
March 14, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28301373/rediscovering-scavenger-receptor-type-bi-surprising-new-roles-for-the-hdl-receptor
#5
Menno Hoekstra, Mary Sorci-Thomas
PURPOSE OF REVIEW: Scavenger receptor BI (SR-BI) is classically known for its role in antiatherogenic reverse cholesterol transport as it selectively takes up cholesterol esters from HDL. Here, we have highlighted recent literature that describes novel functions for SR-BI in physiology and disease. RECENT FINDINGS: A large population-based study has revealed that patients heterozygous for the P376L mutant form of SR-BI showed significantly increased levels of plasma HDL-cholesterol and had increased risk of cardiovascular disease, demonstrating that SR-BI in humans is a significant determinant of cardiovascular disease...
March 15, 2017: Current Opinion in Lipidology
https://www.readbyqxmd.com/read/28300348/sphingosine-1-phosphate-induces-ca-2-signaling-and-cxcl1-release-via-trpc6-channel-in-astrocytes
#6
Hisashi Shirakawa, Rumi Katsumoto, Shota Iida, Takahito Miyake, Takuya Higuchi, Takuya Nagashima, Kazuki Nagayasu, Takayuki Nakagawa, Shuji Kaneko
A biologically active lipid, sphingosine-1-phosphate (S1P) is highly abundant in blood, and plays an important role in regulating the growth, survival, and migration of many cells. Binding of the endogenous ligand S1P results in activation of various signaling pathways via G protein-coupled receptors, some of which generates Ca(2+) mobilization. In astrocytes, S1P is reported to evoke Ca(2+) signaling, proliferation, and migration; however, the precise mechanisms underlying such responses in astrocytes remain to be elucidated...
March 16, 2017: Glia
https://www.readbyqxmd.com/read/28300069/extracellular-%C3%AE-synuclein-induces-sphingosine-1-phosphate-receptor-subtype-1-uncoupled-from-inhibitory-g-protein-leaving-%C3%AE-arrestin-signal-intact
#7
Lifang Zhang, Taro Okada, Shaymaa Mohamed Mohamed Badawy, Chihoko Hirai, Taketoshi Kajimoto, Shun-Ichi Nakamura
Parkinson's disease (PD) is the second most common neurodegenerative disorder. The presence of α-synuclein (α-Syn)-positive intracytoplasmic inclusions, known as Lewy bodies, is the cytopathological hallmark of PD. Increasing bodies of evidence suggest that cell-to-cell transmission of α-Syn plays a role in the progression of PD. Although extracellular α-Syn is known to cause abnormal cell motility, the precise mechanism remains elusive. Here we show that impairment of platelet-derived growth factor-induced cell motility caused by extracellular α-Syn is mainly attributed to selective inhibition of sphingosine 1-phosphate (S1P) signalling...
March 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28297574/bioactive-lipids-and-circulating-progenitor-cells-in-patients-with-cardiovascular-disease
#8
Salim S Hayek, Yuri Klyachkin, Ahmed Asfour, Nima Ghasemzadeh, Mosaab Awad, Iraj Hesaroieh, Hina Ahmed, Brandon Gray, Jinhee Kim, Edmund K Waller, Arshed A Quyyumi, Ahmed K Abdel-Latif
Bone marrow-derived progenitor cells are mobilized into the peripheral blood after acute myocardial injury and in chronic ischemic heart disease. However, the mechanisms responsible for this mobilization are poorly understood. We examined the relationship between plasma levels of bioactive lipids and number of circulating progenitor cells (CPCs) in patients (N = 437) undergoing elective or emergent cardiac catheterization. Plasma levels of sphingosine-1 phosphate (S1P) and ceramide-1 phosphate (C1P) were quantified using mass spectrometry...
March 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28291340/modulators-of-sphingosine-1-phosphate-pathway-biology-recent-advances-of-sphingosine-1-phosphate-receptor-1-s1p1-agonists-and-future-perspectives
#9
Alaric J Dyckman
The sphingoid base derived class of lipids (sphingolipids) is a family of interconverting molecules that play key roles in numerous structural and signaling processes. The biosynthetic pathway of the sphingolipids affords many opportunities for therapeutic intervention: targeting the ligands directly, targeting the various proteins involved in the interconversion of the ligands, or targeting the receptors that respond to the ligands. The focus of this article is on the most advanced of the sphingosine-related therapeutics, agonists of sphingosine-1-phosphate receptor 1 (S1P1)...
March 14, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28288846/pleiotropic-fty720-is-a-specific-and-potent-therapy-for-hypertrophic-scars
#10
Fen Shi, Xiaoling Cao, Zhicheng Hu, Da Ma, Dong Guo, Jian Zhang, Changlin Zhang, Peng Liu, Shanqiang Qu, Jiayuan Zhu, Wuguo Deng, Bing Tang
Hypertrophic scars (HS) is a fibrotic skin condition characterized by aberrant fibroblast phenotypes and excessive deposition of extracellular matrix components. 2-Amino-2-[2-(4-octylphenyl)]-1, 3-propanediol hydrochloride (FTY720), an immunomodulator approved for treating multiple sclerosis, is reported to attenuate fibrosis in multiple disease models. Here we found that FTY720 could significantly attenuate the proliferation and fibrosis in HS fibroblasts (HSFs) as well as in animal HS model. Upon treating HSFs or normal dermal fibroblasts (NFs) with FTY720 at different concentrations for different time periods, we found that FTY720 presented a pleiotropic effect specifically on HSFs, but not NFs, including reducing cell viability, arresting cell cycle progression at G0/G1 phase, promoting apoptosis, inhibiting migration and contraction, and suppressing the expressions of α-smooth muscle actin (α-SMA), collagen I, and collagen III...
March 10, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28287856/enzymatic-kinetics-regarding-reversible-metabolism-of-cs-0777-a-sphingosine-1-phosphate-receptor-modulator-via-phosphorylation-and-dephosphorylation-in-humans
#11
Shin-Ichi Inaba, Maki Yamaguchi-Goto, Kaoru Tanaka-Takanaka, Kiyoaki Yonesu, Hidetaka Sakurai, Kazuishi Kubota, Takashi Izumi
1. CS-0777, a candidate compound for autoimmune diseases, becomes phosphorylated active metabolite, M1, by fructosamine 3-kinase (FN3K), FN3K-related protein (FN3K-RP); and M1 reverted back to CS-0777 by alkaline phosphatase (ALP) in the body. We performed enzyme kinetic analysis of phosphorylation of CS-0777 by FN3K, FN3K-RP, human erythrocytes and human platelets; and dephosphorylation of M1 by various ALP isozymes and human liver, kidney, lung and small intestine microsomes. 2. The Michaelis constants of human FN3K, FN3K-RP, and erythrocytes for CS-0777 phosphorylation were in the range from 498 μM to 1060 μM...
March 13, 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/28284213/mathematical-modelling-and-a-systems-science-approach-to-describe-the-role-of-cytokines-in-the-evolution-of-severe-dengue
#12
S D Pavithra Jayasundara, S S N Perera, Gathsaurie Neelika Malavige, Saroj Jayasinghe
BACKGROUND: Dengue causes considerable morbidity and mortality in Sri Lanka. Inflammatory mediators such as cytokines, contribute to its evolution from an asymptotic infection to severe forms of dengue. The majority of previous studies have analysed the association of individual cytokines with clinical disease severity. In contrast, we view evolution to Dengue Haemorrhagic Fever as the behaviour of a complex dynamic system. We therefore, analyse the combined effect of multiple cytokines that interact dynamically with each other in order to generate a mathematical model to predict occurrence of Dengue Haemorrhagic Fever...
March 11, 2017: BMC Systems Biology
https://www.readbyqxmd.com/read/28283249/sphingosine-1-phosphate-signaling-in-inflammatory-bowel-disease
#13
REVIEW
Ole Haagen Nielsen, Yuan Li, Bengt Johansson-Lindbom, Mehmet Coskun
An unmet medical need exists for the development of targeted therapies for the treatment of inflammatory bowel disease (IBD) with easily administered and stable oral drugs, particularly as most patients on biologics [i.e., tumor necrosis factor (TNF) inhibitors and anti-integrins] are either primary non-responders or lose responsiveness during maintenance treatment. A new class of small molecules, sphingosine-1-phosphate (S1P) receptor modulators, has recently shown efficacy in IBD. Here we provide an overview of the mechanism of action of this novel treatment principle in the context of intestinal inflammation...
March 7, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28279838/modulation-of-sphingosine-1-phosphate-in-inflammatory-bowel-disease
#14
REVIEW
Laurent Peyrin-Biroulet, Ronald Christopher, Dominic Behan, Cheryl Lassen
Inflammatory bowel diseases (IBD), including ulcerative colitis and Crohn's disease, involve an inappropriate immune reaction in the digestive tract, causing a variety of disabling symptoms. The advent of monoclonal antibodies (anti-tumor necrosis factor, anti-integrin, anti-interleukin -23) has revolutionized IBD management. Nevertheless, these agents, with potential for immunogenicity, are associated with high rates of response loss and disease relapse over time. They are also associated with high production costs...
March 6, 2017: Autoimmunity Reviews
https://www.readbyqxmd.com/read/28277139/sphingosine-1-phosphate-activates-the-akt-pathway-to-inhibit-chemotherapy-induced-human-granulosa-cell-apoptosis
#15
Shuyi Li, Jianling Chen, Xiaoling Fang, Xiaomeng Xia
To investigate whether sphingosine-1-phosphate (S1P), an apoptosis-inhibitor would be able to inhibit chemotherapy induced human granulosa cell apoptosis. Cultures of primary granulosa cells were isolated from women undergoing in vitro fertilization (IVF). MTT assay was used to measure the optimum concentration of CTX and S1P acts on human granulosa cells. Granulosa cells were added with pertussis toxin (PTX), the PI3K inhibitor LY294002. Western blot analysis was used to analyze the signaling pathway of proteins and cell apoptosis...
February 21, 2017: Gynecological Endocrinology
https://www.readbyqxmd.com/read/28276483/vascular-transcriptome-profiling-identifies-sphingosine-kinase-1-as-a-modulator-of-angiotensin-ii-induced-vascular-dysfunction
#16
Mateusz Siedlinski, Ryszard Nosalski, Piotr Szczepaniak, Agnieszka H Ludwig-Gałęzowska, Tomasz Mikołajczyk, Magdalena Filip, Grzegorz Osmenda, Grzegorz Wilk, Michał Nowak, Paweł Wołkow, Tomasz J Guzik
Vascular dysfunction is an important phenomenon in hypertension. We hypothesized that angiotensin II (AngII) affects transcriptome in the vasculature in a region-specific manner, which may help to identify genes related to vascular dysfunction in AngII-induced hypertension. Mesenteric artery and aortic transcriptome was profiled using Illumina WG-6v2.0 chip in control and AngII infused (490 ng/kg/min) hypertensive mice. Gene set enrichment and leading edge analyses identified Sphingosine kinase 1 (Sphk1) in the highest number of pathways affected by AngII...
March 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28275141/cutting-edge-targeting-epithelial-ormdl3-increases-rather-than-reduces-airway-responsiveness-and-is-associated-with-increased-sphingosine-1-phosphate
#17
Marina Miller, Arvin B Tam, James L Mueller, Peter Rosenthal, Andrew Beppu, Ruth Gordillo, Matthew D McGeough, Christine Vuong, Taylor A Doherty, Hal M Hoffman, Maho Niwa, David H Broide
In this study, we used cre-lox techniques to generate mice selectively deficient in ORMDL3 in airway epithelium (Ormdl3(Δ2-3/Δ2-3)/CC10) to simulate an inhaled therapy that effectively inhibited ORMDL3 expression in the airway. In contrast to the anticipated reduction in airway hyperresponsiveness (AHR), OVA allergen-challenged Ormdl3(Δ2-3/Δ2-3)/CC10 mice had a significant increase in AHR compared with wild-type mice. Levels of airway inflammation, mucus, fibrosis, and airway smooth muscle were no different in Ormdl3(Δ2-3/Δ2-3)/CC10 and wild-type mice...
March 8, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28273090/fingolimod-effects-in-neuroinflammation-regulation-of-astroglial-glutamate-transporters
#18
De-Hyung Lee, Silvia Seubert, Konstantin Huhn, Lukas Brecht, Caroline Rötger, Anne Waschbisch, Johannes Schlachetzki, Alice Klausmeyer, Arthur Melms, Stefan Wiese, Jürgen Winkler, Ralf A Linker
Fingolimod is an oral sphingosine-1-phosphate-receptor modulator which reduces the recirculation of immune cells and may also directly target glial cells. Here we investigate effects of fingolimod on expression of astroglial glutamate transporters under pro-inflammatory conditions. In astrocyte cell culture, the addition of pro-inflammatory cytokines led to a significant downregulation of glutamate transporters glutamate transporter-1 (slc1a2/SLC1A2) and glutamate aspartate transporter (slc1a3/SLC1A3) expression on the mRNA or protein level...
2017: PloS One
https://www.readbyqxmd.com/read/28271527/the-role-of-lncrna-h19-in-gender-disparity-of-cholestatic-liver-injury-in-mdr2-mice
#19
Xiaojiaoyang Li, Runping Liu, Jing Yang, Lixin Sun, Luyong Zhang, Zhenzhou Jiang, Puneet Puri, Emily C Gurley, Guanhua Lai, Yuping Tang, Zhiming Huang, William M Pandak, Phillip B Hylemon, Huiping Zhou
The multi-drug resistance 2 knockout (Mdr2(-/-) ) mouse is a well-established model of cholestatic cholangiopathies. Female Mdr2(-/-) mice develop more severe hepatobiliary damage than male Mdr2(-/-) mice, which is correlated with a higher proportion of taurocholate (TCA) in bile. Although estrogen has been identified as an important player in intrahepatic cholestasis, the underlying molecular mechanisms of gender-based disparity of cholestatic injury remain unclear. The long non-coding RNA H19 is an imprinted, maternally expressed and estrogen-targeted gene, which is significantly induced in human fibrotic/cirrhotic liver and bile duct ligated mouse liver...
March 8, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28271451/the-utility-of-biomarkers-in-osteoporosis-management
#20
REVIEW
Patrick Garnero
The measurement of bone turnover markers is useful for the clinical investigation of patients with osteoporosis. Among the available biochemical markers, the measurements of serum procollagen type I N-terminal propeptide (PINP) and the crosslinked C-terminal telopeptide (serum CTX) have been recommended as reference markers of bone formation and bone resorption, respectively. The important sources of preanalytical and analytical variability have been identified for both markers, and precise measurement can now be obtained...
March 7, 2017: Molecular Diagnosis & Therapy
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