Sphingosine-1-phosphate and its receptors may be involved in vascular smooth muscle cell (VSMC) proliferation following vascular injury. Here, we evaluate the effect of d-erythro-N,N-dimethylsphingosine (DMS), a sphingosine kinase (SK) inhibitor, on VSMC proliferation, apoptosis and neointimal formation. Growth responses in vitro to fetal calf serum (FCS) were measured by [3H]-thymidine incorporation and extracellular signal-regulated kinase-1/2 (ERK-1/2) activation in quiescent primary cultures of porcine VSMC in the presence and absence of various concentrations of the SK inhibitor DMS. In vivo treatment with DMS was delivered with a local endoluminal catheter, following balloon injury of coronary arteries. The artery intimal formation was investigated by angiography, myography and histomorphometry. In vitro experiments indicated that DMS induced a dose-dependent reduction in [3H]-thymidine incorporation and ERK-1/2 activation via a protein kinase C (PKC) independent mechanism with an IC50 ...
The levels of the bioactive sphingolipid sphingosine-1-phosphate (S1P) are controlled by its synthesis (conversion of sphingosine to S1P, catalyzed by the 2 isoforms of sphingosine kinase SK1 and SK2) and removal (by cleavage of S1P catalyzed by S1P lyase or dephosphorylation catalyzed by S1P phosphatase; ref. 1). S1P binds to S1P-specific G-protein-coupled receptors termed S1P1-5 (1). S1P also binds to intracellular protein targets (see later).. There is evidence of a major role for sphingosine kinase in human cancers. For instance, there is elevated SK1 mRNA transcript and/or SK1 protein expression in stomach, lung, brain, colon, kidney, and breast cancers and non-Hodgkin lymphoma (1). Indeed, we reported that high tumor expression of SK1 is correlated with poor patient survival rates and induction of tamoxifen resistance in patients with estrogen receptor (ER)-positive breast cancer (n = 304; refs. 2, 3). Moreover, S1P promotes migration of ER+ MCF-7 breast cells via an SK1-dependent ...
Exogenous sphingosine 1-phosphate (S1P), like lysophosphatidic acid (LPA), induced neurite retraction or cell rounding in differentiated PC12 cells. The lysosphingolipid-induced shape change was detected at as low as 1 nM; however, a significant accumulation of intracellular S1P was not detected unt …
EC 2.7.1.91. Accepted name: sphingosine kinase. Reaction: ATP + a sphingoid base = ADP + a sphingoid base 1-phosphate. Other name(s): SPHK1 (gene name); SPHK2 (gene name); dihydrosphingosine kinase; dihydrosphingosine kinase (phosphorylating); sphingosine kinase (phosphorylating); sphingoid base kinase; sphinganine kinase; ATP:sphinganine 1-phosphotransferase. Systematic name: ATP:sphingoid base 1-phosphotransferase. Comments: The enzyme is involved in the production of sphingolipid metabolites. It phosphorylates various sphingoid long-chain bases, such as sphingosine, D-erythro-dihydrosphingosine (sphinganine), phytosphingosine (4-hydroxysphinganine), 4-hydroxy-8-sphingenine, 4,8-sphingadienine and D-threo-dihydrosphingosine and L-threo-dihydrosphingosine. The exact substrate range depends on the species.. Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number: 50864-48-7. References:. 1. Stoffel, W., Heimann, G. and Hellenbroich, B. Sphingosine kinase in blood platelets. ...
TY - JOUR. T1 - Sphingosine kinase 1 is an intracellular effector of phosphatidic acid. AU - Delon, Christine. AU - Manifava, Maria. AU - Wood, Eleanor. AU - Thompson, Dawn. AU - Krugmann, Sonja. AU - Pyne, Susan. AU - Ktistakis, Nicholas T. PY - 2004/10/22. Y1 - 2004/10/22. N2 - Sphingosine kinase 1 (SK1) phosphorylates sphingosine to generate sphingosine 1-phosphate (S1P). Because both substrate and product of the enzyme are potentially important signaling molecules, the regulation of SK1 is of considerable interest. We report that SK1, which is ordinarily a cytosolic enzyme, translocates in vivo and in vitro to membrane compartments enriched in phosphatidic acid (PA), the lipid product of phospholipase D. This translocation depends on direct interaction of SK1 with PA, because recombinant purified enzyme shows strong affinity for pure PA coupled to Affi-Gel. The SK1-PA interaction maps to the C terminus of SK1 and is independent of catalytic activity or of the diacylglycerol kinase-like ...
Sphingolipids are metabolized into bioactive products that include ceramide, sphingosine, and sphingosine-1-phosphate (S1P). Sphingosine Kinase (SK) catalyzes the phosphorylation of the lipid sphingosine, creating S1P. S1P subsequently signals through cell surface G protein-coupled receptors, as well as intracellularly
When Gαi-mediated retention signals are blocked, the lymphocyte-intrinsic requirement for S1P1 during LN egress is partially overcome (Pham et al., 2008). To test whether the lymphocyte egress defect in Lyve-1 Cre+ Sphk-deficient mice occurs via effects on the lymphocytes, we sought to determine if inhibition of Gαi-mediated retention signaling would restore egress. Wild-type lymphocytes were treated ex vivo either with PTX or the nonenzymatic oligomer-B (OB) subunit of PTX as a control using a pulse-loading procedure that allowed treated cells to continue entry into LNs for 2-3 h after being transferred into recipient mice, before complete inhibition of Gαi (Lo et al., 2005; Pham et al., 2008). After 1 d of equilibration, the distribution of transferred cells in host animals was determined. Although the frequency of PTX-treated T cells in lymph was about one third the frequency of OB-treated cells in the control hosts, their frequency was up to eightfold higher than that of OB-treated cells ...
Sphingolipids play critical roles in signal transduction, intercellular membrane trafficking and cell growth. As bioactive sphingolipids, ceramide and sphingosine have been implicated in activating anti-proliferative and apoptotic responses in various cancer cells. Conversely, metabolic conversion of ceramide into sphingosine 1-phosphate, ceramide 1-phosphate and glucosylceramide regulates cell proliferation and suppresses ceramide programmed cell death. Many anticancer drugs and stress-induced agonists have been developed to increase endogenous ceramide levels. Sphingosine/ceramide analogues reportedly enhance antitumor activity and have been proposed as a potential new class of chemotherapeutic agents. Among these, sphingosines with aromatic substituents in the side chain often exhibit stronger biological activity compared to natural sphingosines. While a large number of synthetic pathways to sphingosine analogues have been described in the literature, very few pathways provide analogues with ...
Alzheimers disease (AD) is characterized by the accumulation of β-amyloid (Aβ) peptides and hyperphosphorylated tau protein accompanied by neuronal loss. Aβ accumulation has been associated with an impaired sphingosine 1-phosphate (S1P) metabolism. S1P is generated by sphingosine kinases (SphKs), of which there are two isoenzymes SphK1 and SphK2, and degraded by the sphingosine 1-phosphate lyase (SPL). We previously reported, that both a decrease in SphK1 expression and an increase in SPL expression, correlated with amyloid deposits in the entorhinal cortex of AD brains, suggesting a global loss of pro-survival S1P in AD neurons. SphK2 contribution has also been examined in AD yielding to conflicting results that may reflect the complexity of SphK2 regulation. The subcellular localization of SphK2, hence the compartmentalization of generated S1P, is recognized to play a crucial role in dictating either its pro-survival or pro-apoptotic functions. We therefore aimed at studying the expression of
TY - JOUR. T1 - S1P 3-mediated cardiac fibrosis in sphingosine kinase 1 transgenic mice involves reactive oxygen species. AU - Takuwa, Noriko. AU - Ohkura, Sei Ichiro. AU - Takashima, Shin Ichiro. AU - Ohtani, Keisuke. AU - Okamoto, Yasuo. AU - Tanaka, Tamotsu. AU - Hirano, Kaoru. AU - Usui, Soichiro. AU - Wang, Fei. AU - Du, Wa. AU - Yoshioka, Kazuaki. AU - Banno, Yoshiko. AU - Sasaki, Motoko. AU - Ichi, Ikuyo. AU - Okamura, Miwa. AU - Sugimoto, Naotoshi. AU - Mizugishi, Kiyomi. AU - Nakanuma, Yasuni. AU - Ishii, Isao. AU - Takamura, Masayuki. AU - Kaneko, Shuichi. AU - Kojo, Shosuke. AU - Satouchi, Kiyoshi. AU - Mitumori, Kunitoshi. AU - Chun, Jerold. AU - Takuwa, Yoh. PY - 2010/2. Y1 - 2010/2. N2 - Aims Sphingosine kinase 1 (SPHK1), its product sphingosine-1-phosphate (S1P), and S1P receptor subtypes have been suggested to play protective roles for cardiomyocytes in animal models of ischaemic preconditioning and cardiac ischaemia/reperfusion injury. To get more insight into roles for SPHK1 in ...
Sphingosine 1-phosphate (S1P) is a bioactive lipid that has both physiological and pathophysiological roles. It regulates cellular processes such as proliferation, migration, survival and differentiation and affects all organ systems. S1P not only activates S1P-specific receptors to initiate cellular signalling pathways but also directly regulates specific intracellular target proteins. The therapeutic opportunities surrounding S1P signalling are numerous and exemplified by the recent approval of FTY720 (a sphingosine analogue, Gilenya™) for the treatment of relapsing multiple sclerosis. A major focus of research is to develop small-molecule antagonists/agonists/inhibitors that are specific to the different S1P receptor subtypes and the enzymes that regulate S1P levels. This review describes fundamental aspects of S1P biology with an emphasis on the translational potential of intervention therapeutics.. ...
Polyclonal antibody for Sphingosine Kinase 1/SPHK1 detection. Host: Rabbit.Size: 100μg/vial. Tested applications: IHC-P. Reactive species: Human. Sphingosine Kinase 1/SPHK1 information: Molecular Weight: 42518 MW; Subcellular Localization: Cytoplasm. Nucl
Cell-permeable. SKI-II is selective a non-lipid sphingosine kinase (SK) inhibitor. It displays non-ATP-competitive inhibition of human recombinant GST-SK 1 with an IC50 v
Sphingosine kinase 1 (SphK1), the enzyme that produces the bioactive sphingolipid metabolite, sphingosine-1-phosphate, is a promising new molecular target for therapeutic intervention in cancer and inflammatory diseases. In view of its importance, the main objective of this work was to find new and more potent inhibitors for this enzyme possessing different structural scaffolds than those of the known inhibitors. Our theoretical and experimental study has allowed us to identify two new structural scaffolds (three new compounds), which could be used as starting structures for the design and then the development of new inhibitors of SphK1. Our study was carried out in different steps: virtual screening, synthesis, bioassays and molecular modelling. From our results, we propose a new dihydrobenzo[b]pyrimido[5,4-f]azepine and two alkyl{3-/4-[1-hydroxy-2-(4-arylpiperazin-1-yl)ethyl]phenyl}carbamates as initial structures for the development of new inhibitors. In addition, our molecular modelling ...
Sphingoid bases (sphingosine, dihydrosphingosine and phytosphingosine) have been recently found in the oral cavity where they may serve to fortify innate immunity against commensals and periodontal pathogens. In fact, sphingoid bases have potent antimicrobial activity against Gram- positive and Gram- negative bacteria including oral pathogens like Porphyromonas gingivalis. It is not known whether these lipids are cytotoxic or alter the chemokine and cytokine responses of human dendritic cells, a finding important to their future potential as a therapeutic for treatment of periodontal disease. Objectives: The objective of this study was to determine the effects of sphingoid bases on the cytotoxicity and cytokine responses of human myeloid dendritic cells. Methods: Dendritic cells were treated with sphingoid bases (0.2-80.0 μM) for 16 hours in the presence or absence of 0.02 μM hemagglutinin B, a
Extracellular α-synuclein induces sphingosine 1-phosphate receptor subtype 1 uncoupled from inhibitory G-protein leaving β-arrestin signal intact. Zhang, L., Okada, T., Badawy, S., Hirai, C., Kajimoto, T., Nakamura, SI. Sci Rep. 7:44248 . doi:10.1038/srep44248 (2017). Impairment of PDGF-induced chemotaxis by extracellular α-synuclein through selective inhibition of Rac1 activation. Okada, T., Hirai, C., Badawy, S., Zhang, L., Kajimoto, T., Nakamura, SI. Sci Rep. 6:37810. doi: 10.1038/srep37810 (2016). Sphingosine kinases modulate the secretion of amyloid β precursor protein from SH-SY5Y neuroblastoma cells: the role of α-synuclein.. Jesko, H., Okada, T., Strosznajder, RP., Nakamura, S.. Folia Neuropathol. 52(1), 70-78 (2014). Ongoing activation of sphingosine 1-phosphate receptors mediates maturation of exosomal multivesicular endosomes. Kajimoto, T., Okada, T., Miya, S., Zhang, L., Nakamura, SI. Nat. Commun. 4:2712. doi:10.1038/ncomms3712 (2013). Regulation of synaptic strength by ...
Involved in the production of sphingolipid metabolites. Active on sphingosine, phytosphingosine (PHS, 4-hydroxysphinganine), D-erythro-dihydrosphingosine, D-erythro-sphingosine and trans-4, trans-8-sphingadienine, an LCB found exclusively in plants, but not on N-acetyl-dihydrosphingosine (C2-dihydroceramide) and D-threo-dihydrosphingosine.
Purpose : The roles of Sphingosine kinase 2 (Sphk2), a key regulator of the cell fate dictating Sphingolipid balance, are complex and not well characterized but its dysfunctions has been shown to facilitate the development of various diseases. To decipher the - so far unknown - functions of Sphk2 in retinal vascular diseases, Sphk2 overexpressing mice were used in an experimental model of oxygen-induced retinopathy (OIR). Methods : Neonatal C57BL/6J (WT) and EllaCrexJos5a (humane Sphk2 expressing mice with C57BL/6J background, leading to a general overexpression of Sphk2) were used in the OIR model. Neonates were subjected to 75% O2 for 5 days (postnatal day (P) 7 to 12) and then returned to room air. Lipid analysis by LC-MS/MS (n=4), immunhistochemistry on wholemount (n=12), and paraffin embedded retina slides (n=3) were performed on P12, P14 and P17 old retinae. Avascular areas and neovascularisation (NV) were analysed with Adobe Photoshop and ImageJ. One-way ANOVA was used for statistical ...
S1P1, a high affinity G-protein coupled receptor for bioactive lipid sphingosine 1-phosphate (S1P), regulates various cellular functions. However, little is known about the physiological roles of S1P1. To improve our understanding of the function of S1P1 in vivo, we investigated the role of S1P1 during limb development, S1P1 expression in the adult tissues, and S1P1 function in adult vasculature and angiogenesis. ^ During limb development, S1P1 is expressed in the vasculature and in mesenchymal tissues in the remodeling areas. S1P1 −/− limbs are hypervascularized and cartilage condensation was absent in the digit areas. The expression of VEGF and HIF-1α are highly elevated in S1P 1 −/− limbs. Endothelium specific S1P1 −/− limbs also exhibit same phenotype. These results indicate that impaired vascular function in S1P1 −/− limbs generates tissue hypoxia, resulting in abnormal limb development. ^ In normal adult tissues, S1P1 is ubiquitously expressed in various cell types, including
The development of fingolimod, an unselective functional antagonist of the interactions between sphingosine 1 phosphate (S1P) and sphingosine 1 phosphate receptors (S1PRs), as the first oral therapy for multiple sclerosis (MS) has been a milestone. The parallel intensive research on the role of S1P, sphingosine kinases, and the five known S1PRs, their tissue distribution and expression in physiological and pathological conditions have led to a wide range of interesting findings. The initial focus of this research in the context of developing fingolimod as a treatment of MS has been on its immunological effects. The wide distribution and important roles of sphingosine, its metabolites, and their receptors in the central nervous system (CNS) in general, in myelin, and in all cell types of this organ have spurred interest to examine S1P and its five receptors in the brain as well. The present review will concentrate on the latter area and give a brief overview of what is known about S1P/S1PR ...
Sphingolipids are metabolized into bioactive products that include ceramide, sphingosine, and sphingosine-1-phosphate (S1P). Sphingosine Kinase (SK) catalyzes the phosphorylation of the lipid sphingosine, creating S1P. S1P subsequently signals through cell surface G protein-coupled receptors, as well as intracellularly
A total of 80 naïve Crl:CD(SD) Sprague Dawley P generation rats (10 rats/sex) were randomly assigned to four dose groups (Groups 1 through 4), 10 rats/sex/group. Formulations of the test substance, Bourgeonal, or the control substance, corn oil, were administered orally by gavage once daily beginning before cohabitation, through mating and continuing for at least 28 days (P generation male rats;actual: 42 to 45 doses) or through parturition until Day 14 of lactation (P generation female rats; actual: 38 to 56 doses)at 0 (Control), 0.5, 1, and 5 mg/kg/dose. The following parameters and end points were evaluated in the P generation rats assigned in this study: viability, clinical observations, detailed clinical signs, body weights and body weight changes, food consumption, neurobehavioral evaluations (functional observation battery and motor activity), mating and fertility assessments, organ weights, and macroscopic and microscopic evaluations. P generation females were further evaluated for ...
The TSRI team focused on a family of receptors for a fatty lipid molecule called sphingosine 1-phosphate (S1P) that is produced by platelets those flat, circulating, molecule-filled protoplasmic disks in the blood that are necessary for clotting and by a variety of tissue cells. Sphingosine 1-phosphate acts on a family of receptors called the S1P receptors or the edg receptors, originally defined as endothelial differentiation genes. S1P is produced by endothelial cells and other cells at sites in the body where there is inflammation and where there are inflammatory cytokines like tumor necrosis factor-alpha, for instance. S1P lipids activate the S1P receptors and regulate a range of physiological functions that include cardiovascular function and blood pressure. Rosen and his colleagues previously showed that S1P receptors can also control the recirculation of lymphocytes, a mechanism which was never understood before. Furthermore, they found that either S1P lipids or synthetic chemical ...
The TSRI team focused on a family of receptors for a fatty lipid molecule called sphingosine 1-phosphate (S1P) that is produced by platelets those flat, circulating, molecule-filled protoplasmic disks in the blood that are necessary for clotting and by a variety of tissue cells. Sphingosine 1-phosphate acts on a family of receptors called the S1P receptors or the edg receptors, originally defined as endothelial differentiation genes. S1P is produced by endothelial cells and other cells at sites in the body where there is inflammation and where there are inflammatory cytokines like tumor necrosis factor-alpha, for instance. S1P lipids activate the S1P receptors and regulate a range of physiological functions that include cardiovascular function and blood pressure. Rosen and his colleagues previously showed that S1P receptors can also control the recirculation of lymphocytes, a mechanism which was never understood before. Furthermore, they found that either S1P lipids or synthetic chemical ...
2National Food Institute, Technical University of Denmark, Mørkhøj Bygade 19, DK-2860 Søborg, Denmark. Abstract. Some lipid hydrolysis products such as medium-chained NEFA (MC-NEFA), sphingosine and monoacylglycerols (MAG) possess antibacterial activity, while others, including oleic acid, are essential for the optimal growth of Lactobacillus species. Thus, changes in the concentrations of NEFA and MAG in the distal ileum and colon can potentially selectively modulate the composition of the gut microbiota, especially in early life when lipid absorption efficacy is reduced. As medium-chained fatty acids are enriched in mothers milk, such effects may be highly relevant during gut colonisation. In the present study, we examined the effect of selected NEFA, MAG and sphingosine on the composition of faecal microbial communities derived from infants aged 2-5 months during a 24 h anaerobic in vitro fermentation. We tested lipid mixtures in the concentration range of 0-200 mM, either based on ...
This dihydrosphingosine standard is a mixture of D and L isomers and contains approximately 90% erythro and 10% threo isomers. It is a 16 carbon chain, two carbons shorter than the most prevalent dihydrosphingosine in most animals. However, some animals,
View Notes - Mendelian Genetics-1101 from BIOL 1101 at East Carolina University. outcomes of genotypes when more than one type of gamete is produced • P generation is the parental generation - A
NATURE MEDICINE VOLUME 10 | NUMBER 2 | FEBRUARY 2004 131 activator protein-1, leading to the expression of multiple inflammatory proteins that amplify the inflammatory response. In response to several stimuli, ceramide also induces apoptosis, apparently by activating caspases and inducing clustering of death receptors in the cell membrane5. As if that were not enough, ceramide also has a powerful metabolite, sphingosine 1phosphate (S1P)5. Within cells, S1P can mediate the actions of various intracellular kinases and phosphatases. Extracellular S1P can interact with endothelial differentiation gene Gprotein-coupled receptors, which are highly expressed on endothelial cells and activate multiple signal transduction pathways. S1P can also stimulate the release of PAF from endothelial cells6. Several studies implicate sphingomyelin hydrolysis in acute lung injury, as a mediator of stimulatory factors such as TNF-α, Fas/Apo ligand, acid and ionizing radiation. Lung cells express high levels of sphingolipid
A recent finding showed that ceramide and sphingosine-1-phosphate (S1P) become exposed on the surface of cells treated by photodynamic therapy (PDT) and acquire the capac..
Please search sphingosine 1 phosphate signaling in immunology and infectious diseases in your series! be not all confines have called Unfortunately. Your torque claims followed a verbal or expansive policy.
The lyso-phospholipid sphingosine 1-phosphate modulates lymphocyte trafficking, endothelial development and integrity, heart rate, and vascular tone and maturation by activating G protein-coupled sphingosine 1-phosphate receptors. Here, we present the crystal structure of the sphingosine 1-phosphate receptor 1 fused to T4-lysozyme (S1P(1)-T4L) in complex with an antagonist sphingolipid mimic. Extracellular access to the binding pocket is occluded by the amino terminus and extracellular loops of the receptor. Access is gained by ligands entering laterally between helices I and VII within the transmembrane region of the receptor. This structure, along with mutagenesis, agonist structure-activity relationship data, and modeling, provides a detailed view of the molecular recognition and requirement for hydrophobic volume that activates S1P(1), resulting in the modulation of immune and stromal cell responses ...
Sphingosine kinases (SphKs) play key roles in cell proliferation, migration and inflammation by catalyzing the formation of sphingosine-1-phosphate (S1P). However, the two isoenzymes, SphK1 and SphK2, play only partially overlapping roles in tumor epithelial cells. Our genetic approach (siRNA) revealed that SphK2 knockdown cells had more effects on decreasing cell proliferation and migration than SphK1 knockdown. A novel non-radioactive HPLC method based on florescence was developed to measure the activities of SphK. It revealed the increased SphK1 activity induced by SphK2 knockdown could not rescue the cells from apoptosis. In order to confirm the results from the genetic approach, we developed pharmacological approaches that used SphK isoenzymes selective inhibitors to dissect the functions of SphK isoenzymes. After the structure optimization of the lead compounds identified by high throughput screening, two compounds were identified as SphK inhibitors: ...
View mouse Sphk1 Chr11:116530925-116536675 with: phenotypes, sequences, polymorphisms, proteins, references, function, expression
SphK (sphingosine kinase) is the major source of the bioactive lipid and GPCR (G-protein-coupled receptor) agonist S1P (sphingosine 1-phosphate). S1P promotes cell growth, survival and migration, and is a key regulator of lymphocyte trafficking. Inhibition of S1P signalling has been proposed as a strategy for treatment of inflammatory diseases and cancer.. S1P is an extracellular ligand at five cognate GPCRs, S1PRs and a consequential intracellular lipid intermediate that affects diverse cellular processes including migration, growth and survival. S1P regulates function and trafficking of immune cells, induces angiogenesis and regulates endothelial cell functions, promotes survival and migration of cancer cells, and has been implicated as an important mediator in the pathogenesis of cancer and autoimmune and allergic diseases.. ...
Supplementary MaterialsS1 Fig: Ncr1-specific targeting of ILC1 and IFN- production of conventional and resident NK cells. used in this study with clones, fluorophores, and manufacturers. (XLSX) ppat.1008279.s003.xlsx (13K) GUID:?9CA67F0B-5F89-4C16-A515-5F98497D5D19 Data Availability StatementAll relevant data are within the manuscript and its Supporting Information files. Abstract IFN- is an enigmatic cytokine that shows direct anti-viral effects, confers upregulation of MHC-II and other components relevant for antigen presentation, and that adjusts AST-6 the composition and balance of complex cytokine responses. It is produced during immune responses by innate as well as AST-6 adaptive immune cells and can critically influence the course and outcome of infectious diseases, autoimmunity, and cancer. To selectively analyze the function of innate immune cell-derived IFN-, we generated conditional IFN-OFF mice, in which endogenous IFN- expression is disrupted by a loxP flanked gene trap cassette ...
As a member of the wwPDB, the RCSB PDB curates and annotates PDB data according to agreed upon standards. The RCSB PDB also provides a variety of tools and resources. Users can perform simple and advanced searches based on annotations relating to sequence, structure and function. These molecules are visualized, downloaded, and analyzed by users who range from students to specialized scientists.
The presently disclosed subject matter provides compounds of the formula: (1) and pharmaceutically acceptable salts thereof, wherein R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, R.sub.6, R.sub.7, and
The mechanisms by which sphingosine kinase-1 (SK-1)/sphingosine 1-phosphate (S1P) activation contributes to imatinib resistance in chronic myeloid leukemia (CML) are unknown. We show herein that increased SK-1/S1P enhances ...
Secondary lymphoid organs serve as hubs for the adaptive immune system, bringing together antigen, antigen-presenting cells, and lymphocytes. Two families of G protein-coupled receptors play essential roles in lymphocyte migration through these organs: chemokine receptors and sphingosine-1-phosphate …
Principal Investigator:IKEDA Hitoshi, Project Period (FY):2002 - 2003, Research Category:Grant-in-Aid for Scientific Research (C), Section:一般, Research Field:Gastroenterology
Complete information for SPHK1 gene (Protein Coding), Sphingosine Kinase 1, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
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SPHK1 antibody [C3], C-term (sphingosine kinase 1) for ICC/IF, IHC-P, WB. Anti-SPHK1 pAb (GTX104724) is tested in Human samples. 100% Ab-Assurance.
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Pulmonary tissue damage resulting from influenza virus infection is caused by both the cytolytic activity of the virus and the host immune response. Immune-mediated injury results from T cell-mediated destruction of virus-infected cells and by release of cytokines and chemokines that attract polymorphonuclear leukocytes (PML) and macrophages to the infected site. The cytokines/chemokines potentiate dendritic cell (DC) activation and T cell expansion, which further enhances local damage. Here we report that immune modulation by local administration to the respiratory tract of sphingosine analog AAL-R significantly dampens the release of cytokines and chemokines while maintaining protective neutralizing antibody and cytotoxic T cell responses. As a result there was a marked reduction of infiltrating PML and macrophages into the lung and resultant pulmonary tissue injury. DC maturation was suppressed, which limited proliferation of specific antiviral T cells in the lung and draining lymph nodes. ...
TY - JOUR. T1 - Activation of endothelial cell phospholipase D by sphingosine and sphingosine-1-phosphate.. AU - Natarajan, V.. AU - Jayaram, H. N.. AU - Scribner, W. M.. AU - Garcia, J. G.. PY - 1994/8. Y1 - 1994/8. N2 - We have investigated the activation of phospholipase D (PLD) by sphingosine and its derivatives in bovine pulmonary artery endothelial cells (BPAEC) prelabeled with [32P]orthophosphate or [32P]lyso phospholipids. Sphingosine, in a dose- and time-dependent manner, stimulated the hydrolysis of [32P]phosphatidylcholine (PC) resulting in the production of [32P]phosphatidic acid (PA), suggesting PLD activation. In the presence of ethanol (150 mM), the accumulation of [32P]phosphatidylethanol was also observed. The sphingosine-induced stimulation of PLD activity was not affected by treatment with the protein kinase C (PKC) inhibitor staurosporine or by down-regulation of PKC with TPA and was independent of extracellular Ca2+, suggesting that the PLD activation was independent of PKC ...
Sphingosine kinase 1 is an enzyme that in humans is encoded by the SPHK1 gene. Sphingosine kinase 1 phosphorylates sphingosine to sphingosine-1-phosphate (S1P) SK1 is normally a cytosolic protein but is recruited to membranes rich in phosphatidate (PA), a product of Phospholipase D (PLD ...
TY - JOUR. T1 - Sphingosine 1-phosphate stimulation of the p42/p44 mitogen-activated protein kinase pathway in airway smooth muscle. Role of endothelial differentiation gene 1, c-Src tyrosine kinase and phosphoinositide 3-kinase. AU - Rakhit, S. AU - Conway, A M. AU - Tate, R. AU - Bower, T. AU - Pyne, N J. AU - Pyne, S. PY - 1999/3/15. Y1 - 1999/3/15. N2 - We report here that cultured airway smooth muscle cells contain transcripts of endothelial differentiation gene 1 (EDG-1), a prototypical orphan Gi-coupled receptor whose natural ligand is sphingosine 1-phosphate (S1P). This is consistent with data that showed that S1P activated both c-Src and p42/p44 mitogen-activated protein kinase (p42/p44 MAPK) in a pertussis toxin (PTX)-sensitive manner in these cells. An essential role for c-Src was confirmed by using the c-Src inhibitor, PP1, which markedly decreased p42/p44 MAPK activation. We have also shown that phosphoinositide 3-kinase (PI-3K) inhibitors (wortmannin and LY294002) decreased p42/p44 ...
Several extracellular stimuli activate SK1 (sphingosine kinase type 1) to catalyse the production of sphingosine 1-phosphate a bioactive lipid that functions as both an extracellular ligand for a family group of G-protein-linked DMXAA receptors and as a putative intracellular messenger. improved SK activity by more than 50-collapse in crude membranes while only stimulating cytoplasmic SK activity by 4-collapse. In contrast the overexpression of WT-SK1 (wild-type SK1) as well as that of a construct containing a false myristoylation sequence (A2-Myr-SK1) markedly improved SK activity in both membrane and cytoplasmic compartments. Immunofluorescence confirmed that Rabbit polyclonal to KIAA0494. Myr-SK1 preferentially localized in the plasma membrane whereas WT-SK1 and A2-Myr-SK1 partitioned in cytoplasmic/perinuclear cellular areas. Remarkably Myr-SK1 overexpression significantly decreased the rates of cell proliferation by delaying exit from G0/G1 phase. Moreover manifestation of Myr-SK1 but not ...
Human neutrophils, when exposed to soluble stimuli, aggregate, release oxygenated products of arachidonic acid and generate active oxygen species. Sphingolipid-derived products such as sphingosine and lysosphingolipids have been shown to exert selective actions on a variety of cell types, including neutrophils. Therefore, to determine the structural basis for selective inhibition of neutrophil responses by naturally occurring sphingolipids, seven compounds were prepared by total organic synthesis, and their impact on neutrophils in suspension has been studied. The compounds synthesized included sphingosine, psychosine, lactosyl lysosphingolipid, globotriaosyl (Gb3) lysosphingolipid, galactosyl cerebroside, lactosyl ceramide and Gb3 ceramide. The neutrophil responses studied were aggregation, leukotriene generation and superoxide anion production. When exposed to non-cytotoxic levels of the synthetic compounds, as monitored by exclusion of Trypan Blue, none of the synthetic sphingolipids ...
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Sphingosine 1-phosphate (S1P) is one of several bioactive phospholipids that exert profound mitogenic and morphogenic actions. Originally characterized as a second messenger, S1P is now recognized to achieve many of its effects through cell surface, G protein-coupled receptors. We used a subunit-selective [35S]GTPγS binding assay to investigate whether the variety of actions exerted through Edg-1, a recently identified receptor for S1P, might be achieved through multiple G proteins. We found, employing both Sf9 and HEK293 cells, that Edg-1 activates only members of the Gi family, and not Gs, Gq, G12, or G13. We additionally established that Edg-1 activates Gi in response not only to S1P but also sphingosylphosphorylcholine; no effects of lysophosphatidic acid through Edg-1 were evident. Our assays further revealed a receptor(s) for S1P endogenous to HEK293 cells that mediates activation of G13 as well as Gi. Because several of the biological actions of S1P are assumed to proceed through the ...
To the Editor:. We congratulate Hasegawa et al1 for their innovative and thoroughly conducted study on the neuroprotective effect of the immunomodulatory sphingosine 1-phosphate (S1P) analog FTY720 (fingolimod) in a rat stroke model. Making use of a selective agonist of S1P receptor-1 (S1P1) and an antagonist selective for the sphingosine 1-phosphate receptors S1P1 and S1P3, they identified S1P1 as the crucial receptor that mediates the reduction of lesion size and the improved outcome after treatment with FTY720.. Besides the new mechanistic insight concerning the protective signaling pathway in stroke, this study corroborates the finding that the sphingolipid mediator FTY720 has a strong neuroprotective effect in experimental stroke, which has already been shown in mice by Shichita et al2 and our group.3 Also, Wacker et al4 described that cerebral ischemia induces sphingosine kinase-2, the enzyme responsible for the phosphorylation and thus activation of FTY720, which is abundantly expressed ...
TY - JOUR. T1 - Sphingosine 1-phosphate promotes endothelial cell barrier integrity by Edg-dependent cytoskeletal rearrangement. AU - Garcia, Joe G.N.. AU - Liu, Feng. AU - Verin, Alexander Dmitriyevich. AU - Birukova, Anna. AU - Dechert, Melissa A.. AU - Gerthoffer, William T.. AU - Bamburg, James R.. AU - English, Denis. PY - 2001. Y1 - 2001. N2 - Substances released by platelets during blood clotting are essential participants in events that link hemostasis and angiogenesis and ensure adequate wound healing and tissue injury repair. We assessed the participation of sphingosine 1-phosphate (Sph-1-P), a biologically active phosphorylated lipid growth factor released from activated platelets, in the regulation of endothelial monolayer barrier integrity, which is key to both angiogenesis and vascular homeostasis. Sph-1-P produced rapid, sustained, and dose-dependent increases in transmonolayer electrical resistance (TER) across both human and bovine pulmonary artery and lung microvascular ...
Wirrig , C , McKean , J S , Wilson , H M & Nixon , G F 2016 , Sphingosylphosphorylcholine inhibits macrophage adhesion to vascular smooth muscle cells , Biochemical Pharmacology , vol. 115 , pp. 43-50 . https://doi.org/10.1016/j.bcp.2016.07. ...
Purpose: : Establishing the molecular cues controlling proliferation, survival and development of retina photoreceptors (PhRs) is essential for treating retina neurodegeneration. We have shown that sphingosine-1-phosphate (S1P), which regulates survival in several cell systems as an extracellular and intracellular messenger, promoted PhR survival (ARVO 2007). We now investigated whether S1P stimulates PhR differentiation and proliferation and if docosahexaenoic acid (DHA), which promotes PhR survival and differentiation, and glial derived neurotrophic factor (GDNF), which stimulates proliferation, require S1P synthesis for their effects. Methods: : pure neuronal cultures from rat retina were treated with S1P, [3H]sphingosine, DHA or GDNF, with the sphingosine kinase (SphK) inhibitor DHS to inhibit S1P synthesis, with Brefeldin A (BFA) and with BML-241, a S1P membrane receptor antagonist. Opsin, peripherin and SphK levels were quantitated by immunocytochemistry and Western blot; bromodeoxyuridine ...
Sphingomyelin (SM) and its metabolic products are now known to have second messenger functions in a variety of cellular signaling pathways. Particularly, the sphingolipid metabolites, ceramide (Cer) and sphingosine-1-phosphate (S1P), have emerged as a new class of potent bioactive molecules. Ceramide can be generated de novo or by hydrolysis of membrane sphingomyelin by sphingomyelinase (SMase). Ceramide is subsequently metabolized by ceramidase to generate sphingosine (Sph) which in turn produces S1P through phosphorylation by sphingosine kinases 1 and 2 (SphK1, 2). Both ceramide and S1P regulate cellular responses to stress, with generally opposing effects. S1P functions as a growth and survival factor, acting as a ligand for a family of G protein-coupled receptors, whereas ceramide activates intrinsic and extrinsic apoptotic pathways through receptor-independent mechanisms ...
Background: Sphingosine-1 phosphate (S1P) is a biophospholipid with antiapoptotic properties. Previous experiments suggest protective effects of S1P receptor (S1P-R) agonism against ischemia-reperfusion (I-R) injury in several organs, and also in cardiomyocyte cell culture. Fingolimod (FIN) is the only S1P-R agonist FDA-approved for clinical use in multiple sclerosis. The objective of our study was to determine if S1P-R activation by FIN during ischemia increases myocardial salvage, reduces myocardial infarction (MI) size, and mitigates left ventricular (LV) remodeling in a porcine model of I-R.. Methods: Acute MI was induced in 14 pigs by balloon occlusion of the proximal LAD for 60 min, followed by reperfusion. Animals randomly received FIN 15 minutes prior to reperfusion and then daily for the next 3 days, or saline for controls. Animals were evaluated with cardiac MRI and 3D-echo at 1 week and 1 month post MI. Histology and Western blot analysis were performed after 1 month.. Results: One ...
High Density Lipoproteins (HDL) Interrupt the Sphingosine Kinase Signaling Pathway: A possible Mechanism for Protection Against Atherosclerosis by ...
Absorption The Tmax of fingolimod is 12-16 hours. The apparent absolute oral bioavailability is 93%.. Food intake does not alter Cmax or (AUC) of fingolimod or fingolimod-phosphate. Therefore, GILENYA may be taken without regard to meals.. Steady-state blood concentrations are reached within 1 to 2 months following once-daily administration and steady-state levels are approximately 10-fold greater than with the initial dose.. Distribution Fingolimod highly (86%) distributes in red blood cells. Fingolimod-phosphate has a smaller uptake in blood cells of , 17%. Fingolimod and fingolimod-phosphate are , 99.7% protein bound. Fingolimod and fingolimod-phosphate protein binding is not altered by renal or hepatic impairment. Fingolimod is extensively distributed to body tissues with a volume of distribution of about 1200 ± 260 L. Metabolism The biotransformation of fingolimod in humans occurs by 3 main pathways: by reversible stereoselective phosphorylation to the pharmacologically active ...
Pharmacokinetic Analysis of β-Glucan After Administration of PGG-Glucan, a Novel Immunomodulator Being Developed for the Treatment of Non-Small Cell Lung Cancer ...
Effects of a novel immunomodulator in HIV infected individuals. Международная деятельность. Экомед
Our key finding is that concentrations of SPC insufficient to cause vasoconstriction or elevation of [Ca2+]i in IPA can nevertheless substantially enhance vasoconstriction elicited by other means. Such concentrations (300 to 1000 nmol/L) are ,10-fold smaller than the EC50 reported for SPC-induced vasoconstriction, per se, or, indeed, most other actions of SPC (≈12 μmol/L)1,2,4-6 and are consequently much closer to those reported for plasma.11 Notably, SPC was stereospecific for the effects elicited by both high and low concentrations, implying that both are receptor mediated (Figure 2A).. The signaling pathways underlying potentiation of IPA vasoreactivity by ≤1 μmol/L of SPC differ from those underlying vasoconstriction to higher concentrations. We have shown that the latter is mediated by increased RhoK-mediated Ca2+ sensitivity and activation of the 2-APB-sensitive, voltage-independent Ca2+ entry pathway but is independent of Ca2+ release from stores and PLC.4 In contrast, the ...
Sphingosine-1-phosphate receptor 1 (S1P receptor 1 or S1P1), also known as endothelial differentiation gene 1 (EDG1) is a protein that in humans is encoded by the S1PR1 gene. S1PR1 is a G-protein-coupled receptor which binds the bioactive signaling molecule sphingosine 1-phosphate (S1P). S1PR1 belongs to a sphingosine-1-phosphate receptor subfamily comprising five members (S1PR1-5). S1PR1 was originally identified as an abundant transcript in endothelial cells and it has an important role in regulating endothelial cell cytoskeletal structure, migration, capillary-like network formation and vascular maturation. In addition, S1PR1 signaling is important in the regulation of lymphocyte maturation, migration and trafficking. S1PR1 like the other members of the GPCR family is composed of seven-transmembrane helices arranged in a structurally conserved bundle. As well as the other GPCRs, in the extracellular region S1PR1 is composed of three loops: ECL1 between helices II and III, ECL2 between helices ...
TY - JOUR. T1 - The development and maintenance of paclitaxel-induced neuropathic pain require activation of the sphingosine 1-phosphate receptor subtype 1. AU - Janes, Kali. AU - Little, Joshua W.. AU - Li, Chao. AU - Bryant, Leesa. AU - Chen, Collin. AU - Chen, Zhoumou. AU - Kamocki, Krzysztof. AU - Doyle, Timothy. AU - Snider, Ashley. AU - Esposito, Emanuela. AU - Cuzzocrea, Salvatore. AU - Bieberich, Erhard. AU - Obeid, Lina. AU - Petrache, Irina. AU - Nicol, Grant. AU - Neumann, William L.. AU - Salvemini, Daniela. PY - 2014/7/25. Y1 - 2014/7/25. N2 - The ceramide-sphingosine 1-phosphate (S1P) rheostat is important in regulating cell fate. Several chemotherapeutic agents, including paclitaxel (Taxol), involve pro-apoptotic ceramide in their anticancer effects. The ceramide-to-S1P pathway is also implicated in the development of pain, raising the intriguing possibility that these sphingolipids may contribute to chemotherapyinduced painful peripheral neuropathy, which can be a critical ...
The authors investigated if plasma Sphingosine 1-Phosphate (S1P) levels were a predictor for osteoporotic vertebral fracture (VF) risk. They found that S1P leve
The S1P-S1P1 signaling axis represents one of the most critical regulators of lymphocyte trafficking, yet little is known about the in vivo dynamics of S1P1 in response to ligand binding. Studies have identified a cyclical pattern of lymphocyte S1P1 expression: increased in lymphoid organs, decreased or absent in peripheral circulation. However, the signaling properties within this pattern, i.e., whether S1P1 surface expression is a necessary determinant of lymphoid residence, have been difficult to elucidate in the in vivo context. The diversity of GPCR signal regulation further complicates the issue. Agonist-induced internalization of GPCRs is believed to be important in a variety of signaling modalities (Hanyaloglu and von Zastrow, 2008; Marchese et al., 2008). In the case of some receptors, cells become unresponsive to agonists after a significant fraction of receptors are internalized (Vroon et al., 2006). Additionally, endocytosed receptors may carry out unique signaling functions in the ...
Fingolimod (FTY720, Gilenya), an immunosuppresive agent with activity purported to be mediated by binding of its phosphorylated derivative to the sphingosine-1-phosphate receptor 1 (S1P1), was approved earlier in the year as the first orally administered disease modifying therapy for the treatment of relapsing forms of multiple sclerosis. Activation of S1P1 induces internalisation and degradation of the…
BioAssay record AID 504918 submitted by The Scripps Research Institute Molecular Screening Center: Late-stage fluorescence-based dose-response cell-based counterscreen assay to identify agonists of the Sphingosine 1-Phosphate Receptor 4 (S1P4): inhibition by S1P4-selective antagonist 0.4 nM.
sphingosine: A basic, long-chain, unsaturated amino alcohol, C18H37NO2, found combined with lipids in the brain and in nerve tissue.
A Spingosine-1-phosphate Receptor-2 (S1pr2) knockout mouse.. Sphingosine-1-phosphate (S1P), a sphingolipid metabolite, activates cell signaling by interacting with a family of G-protein-coupled cell-surface S1P receptors that activate different and overlapping signaling pathways. Three S1P receptors (S1P1, S1P2 and S1P3) are abundant in embryonic endothelial cells. S1P1 knockouts are embryonic lethals because of hemorrhage. S1P2 null mice did not exhibit embryonic lethality or phenotypic abnormalities. However, double null embryos (S1P1 S1P2 and S1P2 S1P3), and triple null embryos (S1P1 S1P2 S1P3) displayed a more severe vascular phenotype than did S1P1 null embryos, suggesting cooperative functions of the three S1P receptors.. ...
Dr. Spiegel is my guardian angel and I owe her and her entire team and staff a debt of gratitude that I will ever be able to repay! I am one year out from my original DIEP flap surgery with her and I feel great, like myself again! After undergoing a prophylactic mastectomy (due to testing positive for the BRCA 2 gene and strong family cancer) and getting breast implants with another doctor, Dr. Spiegel saved my life by removing the implants and performing DEIP surgery. The implants cased me so much pain and diminished my quality of life but now I have it back. I have no more pain and my breasts are soft again and created from my very own tissue. Thank you Dr. Spiegel! ...
The first edition of Der Spiegel was published in Hanover on Saturday, 4 January 1947.[8] Its release was initiated and sponsored by the British occupational administration and preceded by a magazine titled Diese Woche (meaning This Week in English),[8] which had first been published in November 1946. After disagreements with the British, the magazine was handed over to Rudolf Augstein as chief editor, and was renamed Der Spiegel. From the first edition in January 1947, Augstein held the position of editor-in-chief, which he retained until his death on 7 November 2002.. After 1950, the magazine was owned by Rudolf Augstein and John Jahr; Jahrs share merged with Richard Gruner in 1965 to form the publishing company Gruner + Jahr. In 1969, Augstein bought out Gruner + Jahr for DM 42 million and became the sole owner of Der Spiegel. In 1971, Gruner + Jahr bought back a 25% share in the magazine. In 1974, Augstein restructured the company to make the employees shareholders. All employees with more ...
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RecName: Full=Sphingosine 1-phosphate receptor 3; Short=S1P receptor 3; Short=S1P3;AltName: Full=Endothelial differentiation G-protein coupled receptor 3;AltName: Full=Lysophospholipid receptor B3;AltName: Full=Sphingosine 1-phosphate rece ...
Sphingomyelin (SM) and ceramide-phosphoethanolamines (cer-PEs) are related lipids present in mammals and insects, respectively. Owing to the critical roles that cer-PEs play in eukaryotic cellular function, there is a need to develop methods that provide accurate quantitation of these compounds. Results obtained in this study demonstrate that Drosophila contains cer-PEs with unsaturated sphingoid base cores as well as low levels of cer-PEs that possess saturated sphingoid base cores. Specifically, the method developed in this study enabled the quantitation of picogram amounts of cer-PE containing both unsaturated d14:1(Delta4) and d16:1(Delta4) and saturated d14:0 sphingoid base cores. Using this method, cer-PE compounds with both saturated and unsaturated sphingoid base cores were initially identified by neutral loss scanning, followed by quantitation using selected reaction monitoring (SRM) scans. The SRM scans measured a product ion originating from the sphingoid base backbone, rather than from the
sphingosine 1-phosphate 26993-30-6 Precursor and Downstream products, sphingosine 1-phosphate Precursor products, sphingosine 1-phosphate Downstream products ect.
By subjecting immature DCs generated in vitro to different maturation protocols using LPS or TNF-α/PGE2 as stimulant, we observed that the duration of the stimulus and its nature have a profound impact on the regulation of S1P receptor expression. DC maturation in the presence of LPS or TNF-α/PGE2 mimics conditions favoring a subsequent Th1- or Th2-dominated T cell response, respectively. Thus, the differences observed in the expression profile of S1P receptors following these stimuli may well represent part of the information that is imprinted, for example, on tissue-resident DCs mobilized by distinct environmental conditions. Remarkably, however, in nonstimulated immature DCs, we already noted a S1P receptor pattern that diverged from that published by other investigators. Maeda et al. (28) found a predominant S1P4 expression coupled to a lower level of S1P1 and even more decreased amounts of mRNA coding for S1P2 and S1P3 (compare with Fig. 1). Although in vitro-differentiated DCs were ...
Rabbit Polyclonal Anti-Sphingosine 1 phosphate phosphatase 2 Antibody. Validated: WB, IHC, IHC-P. Tested Reactivity: Human. 100% Guaranteed.
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This is the first national study which assessed the cardiac safety of the first dose of Fingolimod (FTY-Gilenya) versus Fingolimod (FTY-Generic) in patients
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Right-wing populist parties in Europe have been gaining strength for years. Now, they hope to use European Parliament elections in May as a springboard for gaining greater influence in the EU. Surveys indicate they may be successful. By DER SPIEGEL Staff
The death of 21 people at the Love Parade in Duisburg on July 24th was far from a random accident. It was the result of a series of failures made by the city, the police and the event organizers. Particularly damning, at the height of the crush, there was no way out. By SPIEGEL Staff
In an earlier posting I reported on a SPIEGEL ONLINE article by Marc Mother-of-all-Bush-haters Pitzke, who had visited the home town of Nick Berg. Pitzke, in his relentless efforts to criticise US President Bush, quoted a neighbor of the Bergs,...
J Am Anim Hosp Assoc. 2010 Sep-Oct;46(5):301-11. Evaluation of the clinical efficacy of pradofloxacin tablets for the treatment of canine pyoderma. Restrepo C, Ihrke PJ, White SD, Spiegel IB, Affolter VK. Abstract A third-generation fluoroquinolone, pradofloxacin (PRA), is currently being developed to treat bacterial infections in dogs. The purpose of this study was to assess…
Shaifta, Y., Snetkov, V. A., Prieto-Lloret, J., Knock, G. A., Smirnov, S. V., Aaronson, P. I. and Ward, J. P. T., 2015. Sphingosylphosphorylcholine potentiates vasoreactivity and voltage-gated Ca2+ entry via NOX1 and reactive oxygen species. Cardiovascular Research ...
Fingolimod (FTY720) HCl(フィンゴリモド、Gilenya)は、0.033nMのIC50によるスフィンゴシン1-リン酸(S1P)受容体拮抗剤です。