An amino alcohol with a long unsaturated hydrocarbon chain. Sphingosine and its derivative sphinganine are the major bases of the sphingolipids in mammals. (Dorland, 28th ed)
Derivatives of PHOSPHATIDIC ACIDS that lack one of its fatty acyl chains due to its hydrolytic removal.
A group of enzymes that transfers a phosphate group onto an alcohol group acceptor. EC 2.7.1.
A subfamily of lysophospholipid receptors with specificity for LYSOSPHINGOLIPIDS such as sphingosine-1-phosphate and sphingosine phosphorylcholine.
Derivatives of propylene glycol (1,2-propanediol). They are used as humectants and solvents in pharmaceutical preparations.
A class of membrane lipids that have a polar head and two nonpolar tails. They are composed of one molecule of the long-chain amino alcohol sphingosine (4-sphingenine) or one of its derivatives, one molecule of a long-chain acid, a polar head alcohol and sometimes phosphoric acid in diester linkage at the polar head group. (Lehninger et al, Principles of Biochemistry, 2nd ed)
Members of the class of neutral glycosphingolipids. They are the basic units of SPHINGOLIPIDS. They are sphingoids attached via their amino groups to a long chain fatty acyl group. They abnormally accumulate in FABRY DISEASE.
A family of G-protein-coupled receptors that bind to specific LYSOPHOSPHOLIPIDS such as lysophosphatidic acid and lysosphinglipids such as sphingosine-1-phosphate. They play an important role in the formation and function of the CARDIOVASCULAR SYSTEM.
Amidohydrolases that are specific for the cleavage of the N-acyl linkage of CERAMIDES. Ceramidases are classified as acidic, neutral or basic according to the optimal pH with which they function.
A class of sphingolipids found largely in the brain and other nervous tissue. They contain phosphocholine or phosphoethanolamine as their polar head group so therefore are the only sphingolipids classified as PHOSPHOLIPIDS.
An intermediate in the biosynthesis of cerebrosides. It is formed by reaction of sphingosine with UDP-galactose and then itself reacts with fatty acid-Coenzyme A to form the cerebroside.
A ceramidase subtype that is active at neutral pH. It is found at high levels within the SMALL INTESTINE and in the BRAIN.
A ceramidase subtype that is active at acid pH. It plays an important role in sphingolipid degradation by catalyzing the lysosomal hydrolysis of ceramide to sphingosine and free fatty acid. Inherited deficiency of acid ceramidase activity results in FARBER LIPOGRANULOMATOSIS.
A group of MYCOTOXINS found in CORN contaminated with FUSARIUM fungus. They are chains of about 20 carbons with acidic ester, acetylamino and sometimes other substituents. They inhibit ceramide synthetase conversion of SPHINGOLIPIDS to CERAMIDES.
An enzyme that catalyzes the hydrolysis of sphingomyelin to ceramide (N-acylsphingosine) plus choline phosphate. A defect in this enzyme leads to NIEMANN-PICK DISEASE. EC 3.1.4.12.
Neutral glycosphingolipids that contain a monosaccharide, normally glucose or galactose, in 1-ortho-beta-glycosidic linkage with the primary alcohol of an N-acyl sphingoid (ceramide). In plants the monosaccharide is normally glucose and the sphingoid usually phytosphingosine. In animals, the monosaccharide is usually galactose, though this may vary with the tissue and the sphingoid is usually sphingosine or dihydrosphingosine. (From Oxford Dictionary of Biochemistry and Molecular Biology, 1st ed)
An enzyme that catalyzes the hydrolysis of a ceramidetrihexoside to a ceramidedihexoside plus galactose.
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
An enzyme that catalyzes the acyltransferase of SPHINGOSINE to N-acylsphingosine using acyl-COENZYME A as donor and COENZYME A as acceptor. The enzyme is mainly localized in the MITOCHONDRIA.
Enzymes that catalyze a reverse aldol condensation. A molecule containing a hydroxyl group and a carbonyl group is cleaved at a C-C bond to produce two smaller molecules (ALDEHYDES or KETONES). EC 4.1.2.
A ceramidase subtype that is active at alkaline pH. It is found at high levels within the SMALL INTESTINE.
A key enzyme in SPHINGOLIPIDS biosynthesis, this enzyme catalyzes the pyridoxal-5'-phosphate-dependent condensation of L-SERINE and PALMITOYL COENZYME A to 3-dehydro-D-sphinganine. The enzyme consists of two different subunits.
Chromatography on thin layers of adsorbents rather than in columns. The adsorbent can be alumina, silica gel, silicates, charcoals, or cellulose. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)
Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.
Cerebrosides which contain as their polar head group a glucose moiety bound in glycosidic linkage to the hydroxyl group of ceramides. Their accumulation in tissue, due to a defect in beta-glucosidase, is the cause of Gaucher's disease.
The largest family of cell surface receptors involved in SIGNAL TRANSDUCTION. They share a common structure and signal through HETEROTRIMERIC G-PROTEINS.
Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.
Compounds possessing both a hydroxyl (-OH) and an amino group (-NH2).
An serine-threonine protein kinase that requires the presence of physiological concentrations of CALCIUM and membrane PHOSPHOLIPIDS. The additional presence of DIACYLGLYCEROLS markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by PHORBOL ESTERS and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters.
Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.
A subclass of ACIDIC GLYCOSPHINGOLIPIDS. They contain one or more sialic acid (N-ACETYLNEURAMINIC ACID) residues. Using the Svennerholm system of abbrevations, gangliosides are designated G for ganglioside, plus subscript M, D, or T for mono-, di-, or trisialo, respectively, the subscript letter being followed by a subscript arabic numeral to indicated sequence of migration in thin-layer chromatograms. (From Oxford Dictionary of Biochemistry and Molecular Biology, 1997)
A phosphomonoesterase involved in the synthesis of triacylglycerols. It catalyzes the hydrolysis of phosphatidates with the formation of diacylglycerols and orthophosphate. EC 3.1.3.4.
An enzyme found mostly in plant tissue. It hydrolyzes glycerophosphatidates with the formation of a phosphatidic acid and a nitrogenous base such as choline. This enzyme also catalyzes transphosphatidylation reactions. EC 3.1.4.4.
Lipids containing at least one monosaccharide residue and either a sphingoid or a ceramide (CERAMIDES). They are subdivided into NEUTRAL GLYCOSPHINGOLIPIDS comprising monoglycosyl- and oligoglycosylsphingoids and monoglycosyl- and oligoglycosylceramides; and ACIDIC GLYCOSPHINGOLIPIDS which comprises sialosylglycosylsphingolipids (GANGLIOSIDES); SULFOGLYCOSPHINGOLIPIDS (formerly known as sulfatides), glycuronoglycosphingolipids, and phospho- and phosphonoglycosphingolipids. (From IUPAC's webpage)
Calcium and magnesium salts used therapeutically in hepatobiliary dysfunction.
Established cell cultures that have the potential to propagate indefinitely.
A tricyclo bridged hydrocarbon.
The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
The rate dynamics in chemical or physical systems.
A specific protein kinase C inhibitor, which inhibits superoxide release from human neutrophils (PMN) stimulated with phorbol myristate acetate or synthetic diacylglycerol.
One of the virulence factors produced by BORDETELLA PERTUSSIS. It is a multimeric protein composed of five subunits S1 - S5. S1 contains mono ADPribose transferase activity.
A phorbol ester found in CROTON OIL with very effective tumor promoting activity. It stimulates the synthesis of both DNA and RNA.
A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.
One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.
Small double-stranded, non-protein coding RNAs (21-31 nucleotides) involved in GENE SILENCING functions, especially RNA INTERFERENCE (RNAi). Endogenously, siRNAs are generated from dsRNAs (RNA, DOUBLE-STRANDED) by the same ribonuclease, Dicer, that generates miRNAs (MICRORNAS). The perfect match of the siRNAs' antisense strand to their target RNAs mediates RNAi by siRNA-guided RNA cleavage. siRNAs fall into different classes including trans-acting siRNA (tasiRNA), repeat-associated RNA (rasiRNA), small-scan RNA (scnRNA), and Piwi protein-interacting RNA (piRNA) and have different specific gene silencing functions.
Systems in which an intracellular signal is generated in response to an intercellular primary messenger such as a hormone or neurotransmitter. They are intermediate signals in cellular processes such as metabolism, secretion, contraction, phototransduction, and cell growth. Examples of second messenger systems are the adenyl cyclase-cyclic AMP system, the phosphatidylinositol diphosphate-inositol triphosphate system, and the cyclic GMP system.
Fatty acid derivatives of glycerophosphates. They are composed of glycerol bound in ester linkage with 1 mole of phosphoric acid at the terminal 3-hydroxyl group and with 2 moles of fatty acids at the other two hydroxyl groups.
A subfamily of lysophospholipid receptors with specificity for LYSOPHOSPHATIDIC ACIDS.
GLYCOSPHINGOLIPIDS with a sulfate group esterified to one of the sugar groups.
A subclass of phospholipases that hydrolyze the phosphoester bond found in the third position of GLYCEROPHOSPHOLIPIDS. Although the singular term phospholipase C specifically refers to an enzyme that catalyzes the hydrolysis of PHOSPHATIDYLCHOLINE (EC 3.1.4.3), it is commonly used in the literature to refer to broad variety of enzymes that specifically catalyze the hydrolysis of PHOSPHATIDYLINOSITOLS.
Glycosphingolipids which contain as their polar head group a lactose moiety bound in glycosidic linkage to the hydroxyl group of ceramide. Their accumulation in tissue, due to a defect in lactosylceramide beta-galactosidase, is the cause of lactosylceramidosis.
A ganglioside present in abnormally large amounts in the brain and liver due to a deficient biosynthetic enzyme, G(M3):UDP-N-acetylgalactosaminyltransferase. Deficiency of this enzyme prevents the formation of G(M2) ganglioside from G(M3) ganglioside and is the cause of an anabolic sphingolipidosis.
Benzoic acids, salts, or esters that contain an amino group attached to carbon number 4 of the benzene ring structure.
A phorbol ester found in CROTON OIL which, in addition to being a potent skin tumor promoter, is also an effective activator of calcium-activated, phospholipid-dependent protein kinase (protein kinase C). Due to its activation of this enzyme, phorbol 12,13-dibutyrate profoundly affects many different biological systems.
A group of compounds derived from ammonia by substituting organic radicals for the hydrogens. (From Grant & Hackh's Chemical Dictionary, 5th ed)

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. (1/2523)

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 MAPK activation. An essential role for PI-3K was supported by experiments that showed that PI-3K activity was increased in Grb-2 immunoprecipitates from S1P-stimulated cells. Significantly, Grb-2 associated PI-3K activity was decreased by pretreatment of cells with PTX. Finally, we have shown that the co-stimulation of cells with platelet-derived growth factor (PDGF) and S1P (which failed to stimulate DNA synthesis) elicited a larger p42/p44 MAPK activation over a 30 min stimulation compared with each agonist alone. This was associated with a S1P-dependent increase in PDGF-stimulated DNA synthesis. These results demonstrate that S1P activates c-Src and Grb-2-PI-3K (intermediates in the p42/p44 MAPK cascade) via a PTX-sensitive mechanism. This action of S1P is consistent with the stimulation of EDG-1 receptors. S1P might also function as a co-mitogen with PDGF, producing a more robust activation of a common permissive signal transduction pathway linked to DNA synthesis.  (+info)

Activation of integrin and ceramide signalling pathways can inhibit the mitogenic effect of insulin-like growth factor I (IGF-I) in human breast cancer cell lines. (2/2523)

Cell counting, cell cycle analysis and Western immunoblotting were used to examine the effects of non-apoptotic doses of a ceramide analogue, C2, and a synthetic arginine-glycine-aspartic acid (RGD)-containing peptide, RGD, in MCF-7 and T47D cells to determine whether activation of these signalling pathways could alter the mitogenic potential of insulin-like growth factor I (IGF-I). IGF-I alone increased total cell number in both cell lines, associated with a rise in the percentage of cells in the S-phase of the cell cycle and a co-incident increase in cyclin A production. Treatments alone had no effects on cell number or cyclin A production relative to controls. C2 inhibited IGF-I-induced mitogenesis in both lines, whereas RGD was only effective in the T47D line. Despite inhibition of cell proliferation, IGF-I stimulation of cells in S-phase and of cyclin A levels were unaffected; however, an IGF-I-induced increase in cyclin B1 levels was inhibited by 30%. Low-dose induction of integrin and ceramide signalling pathways causes cells to be blocked in S-phase, thereby inhibiting the normal cycle of events associated with the IGF-I-induced mitotic signal. Activating these pathways may not only restrict tumour growth by induction of apoptosis but they may also directly inhibit IGF-I-induced cell proliferation.  (+info)

Na+/H+ antiporter activity in hamster embryos is activated during fertilization. (3/2523)

This study characterized the activation of the regulatory activity of the Na+/H+ antiporter during fertilization of hamster embryos. Hamster oocytes appeared to lack any mechanism for the regulation of intracellular pH in the acid range. Similarly, no Na+/H+ antiporter activity could be detected in embryos that were collected from the reproductive tract between 1 and 5 h post-egg activation (PEA). Activity of the Na+/H+ antiporter was first detected in embryos collected at 5.5 h PEA and gradually increased to reach maximal activity in embryos collected at 7 h PEA. Parthenogenetically activated one-cell and two-cell embryos demonstrate Na+/H+ antiporter activity, indicating that antiporter activity is maternally derived and initiated by activation of the egg. The inability of cycloheximide, colchicine, or cytochalasin D to affect initiation of antiporter activity indicates that antiporter appearance is not dependent on the synthesis of new protein or recruitment of existing protein to the cell membrane. In contrast, incubation of one-cell embryos with sphingosine did inhibit the appearance of Na+/H+ antiporter activity, showing that inhibition of normal protein kinase C activity is detrimental to antiporter function. Furthermore, incubation of oocytes with a phorbol ester which stimulates protein kinase C activity induced Na+/H+ antiporter activity in oocytes in which the activity was previously absent. Incubation with an intracellular calcium chelator also reduced the appearance of antiporter activity. Taken together, these data indicate that the appearance of Na+/H+ antiporter activity following egg activation may be due, at least in part, to regulation by protein kinase C and intracellular calcium levels.  (+info)

Sphingosine 1-phosphate: a prototype of a new class of second messengers. (4/2523)

Sphingosine 1-phosphate (SPP) is an important sphingolipid-derived second messenger in mammalian cells that acts to promote proliferation and to inhibit apoptosis. Various growth factors increase the intracellular concentration of SPP by activating sphingosine kinase, the molecular cloning of which has revealed that it defines a new type of lipid kinase. Cell fate is influenced by the balance between the intracellular concentration of SPP and that of ceramide, a pro-apoptotic sphingolipid metabolite. The observation that a similar "rheostat" is a determinant of cell survival in yeast cells exposed to heat shock indicates that it is an evolutionarily conserved mechanism of stress regulation. SPP also acts extracellularly to inhibit cell motility and to influence cell morphology, effects that appear to be mediated by the G protein-coupled receptor EDG1. These observations indicate that SPP is the prototype of a new class of lipid mediators that exert both intracellular and extracellular actions.  (+info)

Purification and characterization from rat kidney membranes of a novel platelet-activating factor (PAF)-dependent transacetylase that catalyzes the hydrolysis of PAF, formation of PAF analogs, and C2-ceramide. (5/2523)

We have previously identified two enzyme activities that transfer the acetyl group from platelet-activating factor (PAF) in a CoA-independent manner to lysoplasmalogen or sphingosine in HL-60 cells, endothelial cells, and a variety of rat tissues. These were termed as PAF:lysoplasmalogen (lysophospholipid) transacetylase and PAF:sphingosine transacetylase, respectively. In the present study, we have solubilized and purified this PAF-dependent transacetylase 13,700-fold from rat kidney membranes (mitochondrial plus microsomal membranes) based on the PAF:lysoplasmalogen transacetylase activity. The mitochondria and microsomes were prepared and washed three times, then solubilized with 0.04% Tween 20 at a detergent/protein (w/w) ratio of 0.1. The solubilized fractions from mitochondria and microsomes were combined and subjected to sequential column chromatographies on DEAE-Sepharose, hydroxyapatite, phenyl-Sepharose, and chromatofocusing. The enzyme was further purified by native-polyacrylamide gel electrophoresis (PAGE) and affinity gel matrix in which the competitive inhibitor of the enzyme, 1-O-hexadecyl-2-N-methylcarbamyl-sn-glycero-3-phosphoethanolamine was covalently attached to the CH-Sepharose. On SDS-PAGE, the purified enzyme showed a single homogeneous band with an apparent molecular mass of 40 kDa. The purified enzyme catalyzed transacetylation of the acetyl group not only from PAF to lysoplasmalogen forming plasmalogen analogs of PAF, but also to sphingosine producing N-acetylsphingosine (C2-ceramide). In addition, this enzyme acted as a PAF-acetylhydrolase in the absence of lipid acceptor molecules. These results suggest that PAF-dependent transacetylase is an enzyme that modifies the cellular functions of PAF through generation of other diverse lipid mediators.  (+info)

Limited role of ceramide in lipopolysaccharide-mediated mitogen-activated protein kinase activation, transcription factor induction, and cytokine release. (6/2523)

The involvement of ceramide in lipopolysaccharide-mediated activation of mouse macrophages was studied. Lipopolysaccharide, cell-permeable ceramide analogs, and bacterial sphingomyelinase led to phosphorylation of the extracellular signal-regulated kinases, c-Jun NH2-terminal kinases, and p38 kinase and induced AP-1 DNA binding in C3H/OuJ (Lpsn) but not in C3H/HeJ (Lpsd) macrophages. Lipopolysaccharide and ceramide mimetics showed distinct kinetics of mitogen-activated protein kinase phosphorylation and AP-1 induction and activated AP-1 complexes with different subunit compositions. Lipopolysaccharide-activated AP-1 consisted of c-Fos, Jun-B, Jun-D, and c-Jun, while C2-ceramide induced Jun-D and c-Jun only. Lipopolysaccharide and, less potently, C2-ceramide or sphingomyelinase, stimulated AP-1-dependent reporter gene transcription in RAW 264.7 cells. Unlike lipopolysaccharide, C2-ceramide failed to activate NF-kappaB and did not induce production of tumor necrosis factor or interleukin-6. The lipopolysaccharide antagonist, Rhodobacter sphae-roides diphosphoryl lipid A, inhibited lipopolysaccharide activation of NF-kappaB and AP-1 but did not block C2-ceramide-induced AP-1. Pretreatment of C3H/OuJ macrophages with C2-ceramide greatly diminished AP-1 induction following subsequent C2-ceramide stimulation. However, lipopolysaccharide-induced transcription factor activation and cytokine release were not influenced. In contrast, lipopolysaccharide pretreatment inhibited both lipopolysaccharide- and C2-ceramide-mediated responses. Thus, ceramide partially mimics lipopolysaccharide in activating the mitogen-activated protein kinases and AP-1 but not in mediating NF-kappaB induction or cytokine production, suggesting a limited role in lipopolysaccharide signaling.  (+info)

Tumor necrosis factor-alpha, sphingomyelinase, and ceramide inhibit store-operated calcium entry in thyroid FRTL-5 cells. (7/2523)

Tumor necrosis factor alpha (TNF-alpha) is a potent inhibitor of proliferation in several cell types, including thyroid FRTL-5 cells. As intracellular free calcium ([Ca2+]i) is a major signal in activating proliferation, we investigated the effect of TNF-alpha on calcium fluxes in FRTL-5 cells. TNF-alpha per se did not modulate resting [Ca2+]i. However, preincubation (10 min) of the cells with 1-100 ng/ml TNF-alpha decreased the thapsigargin (Tg)-evoked store-operated calcium entry in a concentration-dependent manner. TNF-alpha did not inhibit the mobilization of sequestered calcium. To investigate whether the effect of TNF-alpha on calcium entry was mediated via the sphingomyelinase pathway, the cells were pretreated with sphingomyelinase (SMase) prior to stimulation with Tg. SMase inhibited the Tg-evoked calcium entry in a concentration-dependent manner. Furthermore, an inhibition of calcium entry was obtained after preincubation of the cells with the membrane-permeable C2-ceramide and C6-ceramide analogues. The inactive ceramides dihydro-C2 and dihydro-C6 showed only marginal effects. Neither SMase, C2-ceramide, nor C6-ceramide affected the release of sequestered calcium. C2- and C6-ceramide also decreased the ATP-evoked calcium entry, without affecting the release of sequestered calcium. The effect of TNF-alpha and SMase was inhibited by the kinase inhibitor staurosporin and by the protein kinase C (PKC) inhibitor calphostin C but not by down-regulation of PKC. However, we were unable to measure a significant activation of PKC using TNF-alpha or C6-ceramide. The effect of TNF-alpha was not mediated via activation of either c-Jun N-terminal kinase or p38 kinase. We were unable to detect an increase in the ceramide (or sphingosine) content of the cells after stimulation with TNF-alpha for up to 30 min. Thus, one mechanism of action of TNF-alpha, SMase, and ceramide on thyroid FRTL-5 cells is to inhibit calcium entry.  (+info)

Rational design and synthesis of a novel anti-leukemic agent targeting Bruton's tyrosine kinase (BTK), LFM-A13 [alpha-cyano-beta-hydroxy-beta-methyl-N-(2, 5-dibromophenyl)propenamide]. (8/2523)

In a systematic effort to design potent inhibitors of the anti-apoptotic tyrosine kinase BTK (Bruton's tyrosine kinase) as anti-leukemic agents with apoptosis-promoting and chemosensitizing properties, we have constructed a three-dimensional homology model of the BTK kinase domain. Our modeling studies revealed a distinct rectangular binding pocket near the hinge region of the BTK kinase domain with Leu460, Tyr476, Arg525, and Asp539 residues occupying the corners of the rectangle. The dimensions of this rectangle are approximately 18 x 8 x 9 x 17 A, and the thickness of the pocket is approximately 7 A. Advanced docking procedures were employed for the rational design of leflunomide metabolite (LFM) analogs with a high likelihood to bind favorably to the catalytic site within the kinase domain of BTK. The lead compound LFM-A13, for which we calculated a Ki value of 1.4 microM, inhibited human BTK in vitro with an IC50 value of 17.2 +/- 0.8 microM. Similarly, LFM-A13 inhibited recombinant BTK expressed in a baculovirus expression vector system with an IC50 value of 2.5 microM. The energetically favorable position of LFM-A13 in the binding pocket is such that its aromatic ring is close to Tyr476, and its substituent group is sandwiched between residues Arg525 and Asp539. In addition, LFM-A13 is capable of favorable hydrogen bonding interactions with BTK via Asp539 and Arg525 residues. Besides its remarkable potency in BTK kinase assays, LFM-A13 was also discovered to be a highly specific inhibitor of BTK. Even at concentrations as high as 100 micrograms/ml (approximately 278 microM), this novel inhibitor did not affect the enzymatic activity of other protein tyrosine kinases, including JAK1, JAK3, HCK, epidermal growth factor receptor kinase, and insulin receptor kinase. In accordance with the anti-apoptotic function of BTK, treatment of BTK+ B-lineage leukemic cells with LFM-A13 enhanced their sensitivity to ceramide- or vincristine-induced apoptosis. To our knowledge, LFM-A13 is the first BTK-specific tyrosine kinase inhibitor and the first anti-leukemic agent targeting BTK.  (+info)

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 ...
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 ...
Fingolimod (FTY720) is the first of a novel class: sphingosine 1-phosphate (S1P) receptor modulator and is currently in phase 3 clinical trials for multiple sclerosis (MS). FTY720 was first synthesized in 1992 by chemical modification of an immunosuppressive natural product, ISP-I (myriocin). ISP-I …
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! ...
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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
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。
This study investigated the effects of fingolimod on anti-viral immune response and tissue-trafficking profile of T cell versus other disease modifying
GO:0030148. The chemical reactions and pathways resulting in the formation of sphingolipids, any of a class of lipids containing the long-chain amine diol sphingosine or a closely related base (a sphingoid). ...
October 2004). "Sphingosine kinase 1 is an intracellular effector of phosphatidic acid". J. Biol. Chem. 279 (43): 44763-74. doi ... Olivera A, Rosenthal J, Spiegel S (March 1996). "Effect of acidic phospholipids on sphingosine kinase". J. Cell. Biochem. 60 (4 ... PA acts as a signaling lipid, recruiting cytosolic proteins to appropriate membranes (e.g., sphingosine kinase 1[8]). ...
The major sphingoid base of mammals is commonly referred to as sphingosine. Ceramides (N-acyl-sphingoid bases) are a major ... Hinkovska-Galcheva V, VanWay SM, Shanley TP, Kunkel RG (November 2008). "The role of sphingosine-1-phosphate and ceramide-1- ... These include sphingosine-1-phosphate, a sphingolipid derived from ceramide that is a potent messenger molecule involved in ...
Defects in the enzyme alpha-galactosidase lead to the buildup of globotriaosylceramide, causing Fabry's disease.[3] The pharmaceutical drug migalastat enhances the function of alpha-galactosidase and is used to treat Fabry's. Globotriaosylceramide is also one of the targets of Shiga toxin, which is responsible for pathogenicity of enterohemorrhagic Escherichia coli (EHEC). The bacterial Shiga toxin can be used for targeted therapy of gastric cancer, because this tumor entity expresses the receptor of the Shiga toxin. For this purpose an unspecific chemotherapeutical is conjugated to the B-subunit to make it specific. In this way only the tumor cells, but not healthy cells should be destroyed during therapy.[4] ...
In June 1987, a phase-I clinical trial was launched at Weill Cornell Medical College of Cornell University to study a gene therapy method for treatment of the signs and symptoms of LINCL. The experimental drug works by delivering a gene transfer vector called AAV2CUhCLN2 to the brain.[12] Although the trial is not matched, randomized, or blinded and lacked a contemporaneous placebo/sham control group, assessment of the primary outcome variable suggests a slowing of progression of LINCL in the treated children.[13] Researchers believe the neurological deficits common in JNCL could be due to overactive AMPA receptors in the cerebellum. To test this hypothesis, researchers administered AMPA antagonist drugs into affected mice. The motor skills of the affected mice showed significant improvement after the antagonist treatment, which supported the hypothesis that the neurological deficits in JNCL are due to overactive AMPA receptors. This research could eventually help to alleviate neurological ...
Sphingosine-1-phosphate receptor 2 also known as S1PR2 or S1P2 is a human gene which encodes a G protein-coupled receptor which ... Spiegel S (2000). "Sphingosine 1-phosphate: a ligand for the EDG-1 family of G-protein-coupled receptors". Ann. N. Y. Acad. Sci ... "Entrez Gene: S1PR2, sphingosine-1-phosphate receptor 2". Kempf A, Tews B, Arzt ME, Weinmann O, Obermair FJ, Pernet V, ... 1999). "Differential coupling of the sphingosine 1-phosphate receptors Edg-1, Edg-3, and H218/Edg-5 to the G(i), G(q), and G(12 ...
Stoffel W, LeKim D, Sticht G (December 1968). "Metabolism of sphingosine bases. 8. Distribution, isolation and properties of D- ...
Stoffel W, LeKim D, Heyn G (1970). "Metabolism of sphingosine bases. XIV. Sphinganine (dihydrosphingosine), an effective donor ...
Sphingosine-1-phosphate receptor 5 also known as S1PR5 is a human gene which encodes a G protein-coupled receptor which binds ... "Entrez Gene: S1PR5 Sphingosine-1-phosphate receptor 5". Hobson AD, Harris CM, van der Kam EL, Turner SC, Abibi A, Aguirre AL, ... Ulfig N, Briese M (2005). "Evidence for the presence of the sphingosine-1-phosphate receptor Edg-8 in human radial glial fibers ... A-971432 Sphingosine 1-phosphate receptor agonists: a patent review (2010-2012) Lysophospholipid receptor GRCh38: Ensembl ...
... inhibits sphingosine acyltransferase. Fumonisin B4 and other fumonisins frequently contaminate maize and other ...
There are other Sphingosine-1-phosphate receptor modulators. Van Doorn et al. (2010) observed a strong increase in S1PR1 (and ... Sphingosine-1-phosphate receptor 1 (S1P receptor 1 or S1P1), also known as endothelial differentiation gene 1 (EDG1) is a ... Sphingosine-1-phosphate receptor 1 is also involved in immune-modulation and directly involved in suppression of innate immune ... Lee MJ, Van Brocklyn JR, Thangada S, Liu CH, Hand AR, Menzeleev R, Spiegel S, Hla T (March 1998). "Sphingosine-1-phosphate as a ...
Sphingosine may be phosphorylated to form sphingosine-1-phosphate. This may be dephosphorylated to reform sphingosine. ... The sphingosine backbone is O-linked to a (usually) charged head group such as ethanolamine, serine, or choline.[citation ... Sphingosine Sphingosyl phosphatide Chun J, Hartung HP (2010). "Mechanism of action of oral fingolimod (FTY720) in multiple ... Sphingosine, dihydrosphingosine, and phytosphingosine may be phosphorylated. Ceramides, as a general class, are N-acylated ...
"Sphingosine 1-Phosphate Modulates Spinal Nociceptive Processing". Journal of Biological Chemistry. 283 (47): 32442-32451. doi: ...
Chemically, it is a galactoside of sphingosine. Hawkins-Salsbury, J. A.; Parameswar, A. R.; Jiang, X; Schlesinger, P. H.; ...
PAP is downregulated by sphingosine and dihydrosphingosine. This makes sense in the context of the discussion above. Namely, a ... and sphingosine-1-phosphate, but is not essential in its entirety for the enzyme's native substrate, phosphatidylglycerol ...
These ceramides are synthesized from the acylation of sphingosine. The biosynthetic pathway for sphingosine is found below: As ... Sphingolipids are formed from ceramides that consist of a fatty acid chain attached to the amino group of a sphingosine ... This product is then reduced to form dihydrospingosine, which is converted to sphingosine via the oxidation reaction by FAD. ... Unlike phospholipids, sphingolipids have a sphingosine backbone. Sphingolipids exist in eukaryotic cells and are particularly ...
CS1 maint: discouraged parameter (link) Obinata, Hideru; Hla, Timothy (2012-01-01). "Sphingosine 1-phosphate in coagulation and ... "Plasma gelsolin modulates cellular response to sphingosine 1-phosphate". American Journal of Physiology. Cell Physiology. 299 ( ...
The product sphingosine-1-phosphate (S1P) can be dephosphorylated in the ER to regenerate sphingosine by certain S1P ... 2003). "The sphingosine kinase 1/sphingosine-1-phosphate pathway mediates COX-2 induction and PGE2 production in response to ... S1P is formed by phosphorylation of sphingosine by sphingosine kinase (SK). The phosphate group of the product can be detached ... Hait, N. C.; Oskeritzian, C. A.; Paugh, S. W.; Milstien, S.; Spiegel, S. (2006). "Sphingosine kinases, sphingosine 1 phosphate ...
"Entrez Gene: S1PR3 sphingosine-1-phosphate receptor 3". Hla T, Lee MJ, Ancellin N, et al. (2000). "Sphingosine-1-phosphate ... Sphingosine-1-phosphate receptor 3 also known as S1PR3 is a human gene which encodes a G protein-coupled receptor which binds ... Spiegel S (2000). "Sphingosine 1-phosphate: a ligand for the EDG-1 family of G-protein-coupled receptors". Ann. N. Y. Acad. Sci ... 1999). "Differential coupling of the sphingosine 1-phosphate receptors Edg-1, Edg-3, and H218/Edg-5 to the G(i), G(q), and G(12 ...
2003). "Role of human sphingosine-1-phosphate phosphatase 1 in the regulation of intra- and extracellular sphingosine-1- ... Sphingosine-1-phosphate phosphatase 1 is an enzyme that in humans is encoded by the SGPP1 gene. ENSG00000285281 GRCh38: Ensembl ... "Entrez Gene: SGPP1 sphingosine-1-phosphate phosphatase 1". CS1 maint: discouraged parameter (link) Ogawa C, Kihara A, Gokoh M, ... 2004). "Role of sphingosine-1-phosphate phosphatase 1 in epidermal growth factor-induced chemotaxis". J. Biol. Chem. 279 (33): ...
Sphingosine kinase (SK) is a lipid kinase that catalyzes the conversion of sphingosine to sphingosine-1-phosphate (S1P). ... Upon activation, sphingosine kinase migrates from the cytosol to the plasma membrane where it transfers a γ phosphate (which is ... Neubauer, Heidi A.; Pitson, Stuart M. (November 2013). "Roles, regulation and inhibitors of sphingosine kinase 2". FEBS Journal ... In contrast, the dephosphorylated sphingosine promotes cell apoptosis, and it is therefore critical to understand the ...
... (ABC294640) is a drug which acts as an inhibitor of the enzyme sphingosine kinase 2. It is under development as a ... Lewis CS, Voelkel-Johnson C, Smith CD (2018). "Targeting Sphingosine Kinases for the Treatment of Cancer". Advances in Cancer ...
Sphingosine-1-phosphate receptor 4 also known as S1PR4 is a human gene which encodes a G protein-coupled receptor which binds ... 2003). "The sphingosine 1-phosphate receptor S1P4 regulates cell shape and motility via coupling to Gi and G12/13". J. Cell. ... "Entrez Gene: S1PR4 Sphingosine-1-phosphate receptor 4". Gräler MH, Bernhardt G, Lipp M (1998). "EDG6, a novel G-protein-coupled ... 2000). "Sphingosine-1-phosphate is a ligand for the G protein-coupled receptor EDG-6". Blood. 95 (8): 2624-9. doi:10.1182/blood ...
Most lymphocytes express sphingosine-1-phosphate receptors (S1P1-5), which are G protein-coupled receptors located in the cell ... Garris CS, Blaho VA, Hla T, Han MH (July 2014). "Sphingosine-1-phosphate receptor 1 signalling in T cells: trafficking and ... Cyster JG, Schwab SR (2012). "Sphingosine-1-phosphate and lymphocyte egress from lymphoid organs". Annual Review of Immunology ... membrane that bind to the ligand sphingosine-1-phosphate (S1P). S1P is a sphingolipid metabolite that is abundant in the ...
It is a structural analogue of sphingosine and is phosphorylated by sphingosine kinases in the cell (most importantly ... Paugh SW, Cassidy MP, He H, Milstien S, Sim-Selley LJ, Spiegel S, Selley DE (July 2006). "Sphingosine and its analog, the ... Lahiri S, Park H, Laviad EL, Lu X, Bittman R, Futerman AH (June 2009). "Ceramide synthesis is modulated by the sphingosine ... Its discovery and the following accelerated development of sphingosine 1-phosphate receptor agonists as immunomodulators based ...
This gene encodes one of two sphingosine kinase isozymes that catalyze the phosphorylation of sphingosine into sphingosine 1- ... "IgE-dependent activation of sphingosine kinases 1 and 2 and secretion of sphingosine 1-phosphate requires Fyn kinase and ... "Entrez Gene: Sphingosine kinase 2". Retrieved 2011-12-22. CS1 maint: discouraged parameter (link) Liu H, Sugiura M, Nava VE, ... Hait NC, Sarkar S, Le Stunff H, Mikami A, Maceyka M, Milstien S, Spiegel S (August 2005). "Role of sphingosine kinase 2 in cell ...
Its activity is inhibited by spermine, sphingosine, and several phospholipids. GRCh38: Ensembl release 89: ENSG00000161714 - ...
Taha TA, Mullen TD, Obeid LM (2006). "A house divided: ceramide, sphingosine, and sphingosine-1-phosphate in programmed cell ... Ceramide can be further hydrolyzed by acid ceramidase to form sphingosine and a free fatty acid, both of which are able to ... A ceramide is composed of sphingosine and a fatty acid. Ceramides are found in high concentrations within the cell membrane of ... Third, in the "salvage" pathway, sphingolipids that are broken down into sphingosine are reused by reacylation to form ceramide ...
... is an orally bioavailable selective agonist of sphingosine-1-phosphate receptor 5 (S1PR5) discovered at AbbVie. It was ... Roberts E, Guerrero M, Urbano M, Rosen H (Jul 2013). "Sphingosine 1-phosphate receptor agonists: a patent review (2010-2012)". ... "The use of selective sphingosine-1-phosphate receptor 5 agonists for the treatment of neurodegenerative disorders such as ... An Orally Bioavailable Selective Sphingosine-1-Phosphate Receptor 5 (S1P5) Agonist for the Potential Treatment of ...
"Regulation of autotaxin expression and secretion by lysophosphatidate and sphingosine 1-phosphate". Journal of Lipid Research. ... "Inhibition of autotaxin by lysophosphatidic acid and sphingosine 1-phosphate". The Journal of Biological Chemistry. 280 (22): ...
Sphingosine is the main long-chain base present in ceramide. Galactosylceramide is the principal glycosphingolipid in brain ... The lysosome breaks down the glycosphingolipid to its primary components, fatty acids, sphingosine, and saccharide. Analysis of ... intermolecular hydrogen bonds between the polar hydrogens of the sugar and the hydroxy and amide groups of the sphingosine base ...
Sphingosine kinases (SKs) catalyse the conversion of sphingosine to sphingosine 1-phosphate (S1P), a signalling lipid that is ... Post-translational regulation of sphingosine kinases.. Chan H1, Pitson SM.. Author information. 1. Molecular Signalling ...
Sphingosine kinase, sphingosine-1-phosphate, and apoptosis.. Maceyka M1, Payne SG, Milstien S, Spiegel S. ... The sphingolipid metabolites ceramide (Cer), sphingosine (Sph), and sphingosine-1-phosphate (S1P) play an important role in the ...
Sphingosine can be phosphorylated in vivo via two kinases, sphingosine kinase type 1 and sphingosine kinase type 2. This leads ... sphingosine and sphingosine-1-phosphate, are lipid signaling molecules involved in diverse cellular processes. Sphingosine is ... Structure of sphingosine. J. Biol. Chem. 170: 285-295 Sphingolipidoses General structures of sphingolipids Sphingosine at the ... Sphingosine (2-amino-4-trans-octadecene-1,3-diol) is an 18-carbon amino alcohol with an unsaturated hydrocarbon chain, which ...
0-Sphingosine ceramide analog. Join researchers using high quality Dodecyl sphingosine from Abcam and achieve your mission, ... N-Dodecanoyl-D-erythro-sphingosine (Dodecyl sphingosine), C12:0-Sphingosine ceramide analog (ab144144). ... n-dodecanoyl-d-erythro-sphingosine-dodecyl-sphingosine-c120-sphingosine-ceramide-analog-ab144144.pdf ... N-Dodecanoyl-D-erythro-sphingosine (Dodecyl sphingosine), C12:0-Sphingosine ceramide analog ...
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"The metabolism of sphingosine bases in Tetrahymena pyriformis Sphingosine kinase and sphingosine-1-phosphate lyase". Hoppe- ... from the precursor sphingolipid sphingosine. Sphingolipid metabolites, such as ceramide, sphingosine and sphingosine-1- ... Sphingosine kinase (SphK) is a conserved lipid kinase that catalyzes formation sphingosine-1-phosphate (S1P) ... Maceyka M, Milstien S, Spiegel S (September 2005). "Sphingosine kinases, sphingosine-1-phosphate and sphingolipidomics". ...
Studies of the last two decades have clearly established that sphingosine 1‐phosphate (S1P), considered for many years a mere ... Keywords: sphingosine 1‐phosphate; S1P receptors; G‐protein coupled receptors; sphingosine kinases; ceramide; HDL ; ApoM ; S1P ... 2011) Sphingosine‐1‐phosphate produced by sphingosine kinase 2 in mitochondria interacts with prohibitin 2 to regulate complex ... S1P is generated via phosphorylation of the amino alcohol sphingosine catalysed by sphingosine kinase (SphK), which exists in ...
... Slavica Ribar ; Medicinski fakultet Sveučilišta u Zagrebu, Zavod za kemiju i biokemiju, Šalata 3, ... Sphinganin and sphingosine were determined by means of high-performance liquid chromatography. The results of this research ... The aim of this study was to determine the concentrations of free and total sphinganine and sphingosine in milk (human, cows, ... The concentrations of free sphingosine and sphinganine in cows milk were lower than in human milk. In sheeps and goats milk ...
Sphingosine kinase 1 (SphK1) is a lipid kinase that catalyzes the conversion of sphingosine to sphingosine-1-phosphate (S1P), ... Sphingosine kinase 1 (SphK1) is a lipid kinase that catalyzes the conversion of sphingosine to sphingosine-1-phosphate (S1P), ... Sphingosine kinase 1. A, B, C. 360. Homo sapiens. Mutation(s): 0 Gene Names: SPHK1, SPHK, SPK, SK1. EC: 2.7.1.91 (PDB Primary ... Molecular Basis of Sphingosine Kinase 1 Substrate Recognition and Catalysis.. Wang, Z., Min, X., Xiao, S.H., Johnstone, S., ...
Liu et al. report that sphingosine kinase 2 (SphK2), despite its sequence similarity to SphK1, promotes apoptosis instead of ... NIH 3T3 fibroblasts transfected with either SphK1 or SphK2 showed increased sphingosine 1-phosphate (S1P) production, although ... Sphingosine kinase type 2 is a putative BH3-only protein that induces apoptosis. J. Biol. Chem. 278, 40330-40336 (2003). [ ...
... is a highly conserved lipid kinase that phosphorylates sphingosine to form sphingosine-1-phosphate (S1P). S1P/SphK has been ... Sphingosine kinase (SphK) is a highly conserved lipid kinase that phosphorylates sphingosine to form sphingosine-1-phosphate ( ... An oncogenic role of sphingosine kinase Curr Biol. 2000 Nov 30;10(23):1527-30. doi: 10.1016/s0960-9822(00)00834-4. ...
... pharmaceutical compositions containing them and their use as pharmaceuticals as modulators of sphingosine-1- ... Sphingosine-1 phosphate is stored in relatively high concentrations in human platelets, which lack the enzymes responsible for ... A group of novel azetidine derivatives, which are potent and selective sphingosine-1-phosphate modulators has been discovered. ... This invention describes compounds of Formula I, which have sphingosine-1-phosphate receptor biological activity. The compounds ...
... Z. Qu, Bernice L. Y. Cheuk, and ... Z. Qu, Bernice L. Y. Cheuk, and Stephen W. K. Cheng, "Differential Expression of Sphingosine-1-Phosphate Receptors in Abdominal ...
Sphingosine kinase 1 (SphK1) is a lipid kinase that catalyzes the conversion of sphingosine to sphingosine-1-phosphate (S1P), ... Sphingosine kinase 1 (SphK1) is a lipid kinase that catalyzes the conversion of sphingosine to sphingosine-1-phosphate (S1P), ... Sphingosine kinase 1. A, B, C, D, E, F. 361. Homo sapiens. Mutation(s): 0 Gene Names: SPHK1, SPHK, SPK, SK1. EC: 2.7.1.91 (PDB ... Molecular basis of sphingosine kinase 1 substrate recognition and catalysis.. Wang, Z., Min, X., Xiao, S.H., Johnstone, S., ...
sphingosine: A basic, long-chain, unsaturated amino alcohol, C18H37NO2, found combined with lipids in the brain and in nerve ... The results clearly show that both the sphingosine and fatty-acyl groups of liver c16 ceramide were mostly derived from DNL, ... Figure 7D, the extent of isotopic labeling in the sphingosine and fatty-acyl groups of ceramide molecules was analyzed, where ... The contribution of DNL-derived FA to ceramide synthesis was evaluated based on deuterium labeling of sphingosine - and acyl- ...
This study shows that elevated sphingosine-1-phosphate (S-1-P) levels resulting from increased activity of sphingosine kinase-1 ... Targeting sphingosine kinase-1 to inhibit melanoma Pigment Cell Melanoma Res. 2012 Mar;25(2):259-74. doi: 10.1111/j.1755-148X. ...
J:293101 Chen Q, et al., Angiocrine Sphingosine-1-Phosphate Activation of S1PR2-YAP Signaling Axis in Alveolar Type II Cells Is ... J:49744 Kohama T, et al., Molecular cloning and functional characterization of murine sphingosine kinase. J Biol Chem. 1998 Sep ...
Also acts on D-erythro-sphingosine and to a lesser extent sphinganine, but not other lipids, such as D,L-threo- ... Catalyzes the phosphorylation of sphingosine to form sphingosine 1-phosphate (SPP), a lipid mediator with both intra- and ... Catalyzes the phosphorylation of sphingosine to form sphingosine 1-phosphate (SPP), a lipid mediator with both intra- and ... Sphingosine kinase 1Add BLAST. 384. Amino acid modifications. Feature key. Position(s). DescriptionActions. Graphical view. ...
The sphingosine 1-phosphate receptor 1 (S1P1) and its ligand, sphingosine 1-phosphate (S1P), have now emerged as critical ... Structure of the First Sphingosine 1-Phosphate Receptor Message Subject. (Your Name) has forwarded a page to you from Science ... The lipid sphingosine 1-phosphate may laterally diffuse through the membrane to bind a receptor. ... The lipid sphingosine 1-phosphate may laterally diffuse through the membrane to bind a receptor. ...
Sphingosine kinase (SphK) 1 and 2 phosphorylate sphingosine to generate sphingosine-1-phosphate (S1P), a pluripotent lipophilic ... 2006) IgE-dependent activation of sphingosine kinases 1 and 2 and secretion of sphingosine 1-phosphate requires Fyn kinase and ... S1P is produced by phosphorylation of sphingosine by two related rate-limiting kinases, sphingosine kinase 1 (SphK1) and SphK2 ... 2003) Sphingosine kinase type 2 is a putative BH3-only protein that induces apoptosis. J Biol Chem 278:40330-40336. ...
We identified sphingosine-1-phosphate receptor 2 (S1PR2) as a sex- and strain-specific, disease-modifying molecule that ... Enhanced sphingosine-1-phosphate receptor 2 expression underlies female CNS autoimmunity susceptibility. ... Enhanced sphingosine-1-phosphate receptor 2 expression underlies female CNS autoimmunity susceptibility. ...
It is produced by the phosphorylation of sphingosine by sphingosine kinases (SphKs) and exported out of cells via transporters ... Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid metabolite involved in many critical cell processes. ... It is produced by the phosphorylation of sphingosine by sphingosine kinases (SphKs) and exported out of cells via transporters ... G. M. Strub, M. Paillard, J. Liang et al., "Sphingosine-1-phosphate produced by sphingosine kinase 2 in mitochondria interacts ...
Sphingosine-1-phosphate (S1P) is a lipid mediator that controls cell trafficking and activation. In this review, we focus on ... Immunological Function of Sphingosine 1-Phosphate in the Intestine. Jun Kunisawa 1,2,* and Hiroshi Kiyono 1,2,3,4,* ... Sphingosine-1-phosphate (S1P) is a lipid mediator that controls cell trafficking and activation. In this review, we focus on ... Kunisawa, J.; Kiyono, H. Immunological Function of Sphingosine 1-Phosphate in the Intestine. Nutrients 2012, 4, 154-166. ...
Sphingosine kinases (SphKs) catalyze the conversion of the sphingosine to the promitogenic/migratory product, sphingosine-1- ... Orr Gandy KA and Obeid LM: Targeting the sphingosine kinase/sphingosine 1-phosphate pathway in disease: Review of sphingosine ... Regulation of cellular sphingosine-1-phosphate by sphingosine kinase 1 and sphingosine-1-phopshate lyase determines ... Sphingosine can be phosphorylated by one of two SphKs (SphK1 and SphK2) to form sphingosine-1-phosphate (S1P). The only exit ...
Compare sphingosine-1-phosphate receptor 3 Biomolecules from DiscoverX from leading suppliers on Biocompare. View ... Your search returned 1 sphingosine-1-phosphate receptor 3 Biomolecules across 1 supplier. ...
... sphingosine explanation free. What is sphingosine? Meaning of sphingosine medical term. What does sphingosine mean? ... Looking for online definition of sphingosine in the Medical Dictionary? ... Related to sphingosine: cerebroside, ceramide, sphingomyelin. sphingosine. [sfing´go-sēn] a basic amino alcohol present in ... Sphingosine kinase expression increases intracellular sphingosine-1-phosphate and promotes cell growth and survival.. ...
Receptor for the lysosphingolipid sphingosine 1-phosphate (S1P). S1P is a bioactive lysophospholipid that elicits diverse ... Sphingosine 1-phosphate receptor 3Add BLAST. 378. Amino acid modifications. Feature key. Position(s). DescriptionActions. ... "Sphingosine 1-phosphate-induced cell proliferation, survival, and related signaling events mediated by G protein-coupled ... "Sphingosine 1-phosphate-induced cell proliferation, survival, and related signaling events mediated by G protein-coupled ...
anti-Sphingosine Kinase 1 (SPHK1) Antikörper. Bezeichnung:. anti-Sphingosine Kinase 1 Antikörper (SPHK1). Auf www.antikoerper- ... Mouse (Murine) Sphingosine Kinase 1 (SPHK1) Interaktionspartner * Sphingosine kinase 1 has distinct roles in the activation of ... Weitere Antikörper gegen Sphingosine Kinase 1 Interaktionspartner. Fruit Fly (Drosophila melanogaster) Sphingosine Kinase 1 ( ... Am meisten referenzierte anti-Sphingosine Kinase 1 Antikörper. Show all anti-Sphingosine Kinase 1 (SPHK1) Antikörper with ...
sphingosine, d-erythro-sphingosine, 4-sphingenine, d-sphingosine, sphing-4-enine, cerebroside, sphingenine, 4-trans-sphingenine ... sphingosine, d-erythro-sphingosine, 4-sphingenine, d-sphingosine, sphing-4-enine, cerebroside, sphingenine, 4-trans-sphingenine ... D-erythro-Sphingosine is used to inhibits protein kinase C and calmodulin-dependent enzymes, induces apoptosis. And also used ...
Sphingosine 1-phosphate (S1P) is a bioactive sphingolipid with well-established effects on angiogenesis, carcinogenesis and ... S1P is synthesized by sphingosine kinases (SphKs) and many of its actions are mediated by S1P specific cell surface receptors ( ... S1P is synthesized by sphingosine kinases (SphKs) and many of its actions are mediated by specific cell surface receptors ( ... Sphingosine 1-phosphate (S1P) is a bioactive sphingolipid with well-established effects on angiogenesis, carcinogenesis and ...
  • Sphingosine can be phosphorylated in vivo via two kinases, sphingosine kinase type 1 and sphingosine kinase type 2. (wikipedia.org)
  • Post-translational regulation of sphingosine kinases. (nih.gov)
  • Sphingosine kinases (SKs) catalyse the conversion of sphingosine to sphingosine 1-phosphate (S1P), a signalling lipid that is involved in a plethora of cellular processes including proliferation, apoptosis, calcium homeostasis, angiogenesis, vascular and neuronal maturation, cell migration and immune responses. (nih.gov)
  • Sphingosine kinases (SphKs) types 1 and 2, the two enzymes identified so far in mammals that produce S1P by ATP-dependent phosphorylation of sphingosine, have therefore received considerable interest. (wikipedia.org)
  • It is produced by the phosphorylation of sphingosine by sphingosine kinases (SphKs) and exported out of cells via transporters such as spinster homolog 2 (Spns2). (hindawi.com)
  • Sphingosine kinases (SphKs) catalyze the conversion of the sphingosine to the promitogenic/migratory product, sphingosine-1-phosphate (S1P). (spandidos-publications.com)
  • Sphingosine kinases (SphKs) are biological lipid kinases that regulate the sphingolipid metabolic pathway. (spandidos-publications.com)
  • S1P is synthesized by sphingosine kinases (SphKs) and many of its actions are mediated by S1P specific cell surface receptors (S1P 1-5 ), although different intracellular targets of S1P have been identified. (frontiersin.org)
  • Sphingosine 1-phosphate (S1P) is a bioactive lipid mediator, formed by the phosphorylation of sphingosine by sphingosine kinases (SphKs) 1 and 2, which participates in the regulation of a variety of biological activities in different cell types ( Pitson, 2011 ). (frontiersin.org)
  • Sphingosine kinases (SphKs) play key roles in cell proliferation, migration and inflammation by catalyzing the formation of sphingosine-1-phosphate (S1P). (aacrjournals.org)
  • Sphingosine 1-phosphate (S1P), a lysophospholipid mediator, is generated from sphingosine by sphingosine kinases and binds five known cell surface receptors. (mdpi.com)
  • FTY720 is effectively converted to an active metabolite, FTY720 phosphate (FTY720-P) by sphingosine kinases. (mdpi.com)
  • S1P levels inside cells are tightly regulated by the balance between its synthesis by sphingosine kinases and degradation. (aspetjournals.org)
  • an aliphatic 18-carbon amino alcohol with an unsaturated hydrocarbon chain), by sphingosine kinases ( Fig. 2 ). (aspetjournals.org)
  • 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. (uzh.ch)
  • This study investigated the role that sphingosine kinases (SPHK) and ceramide-derived sphingosine 1-phosphate (S1P) play in adipocyte terminal differentiation. (scirp.org)
  • Acid ceramidase, an enzyme of the sphingolipid metabolic pathway, hydrolyzes the antiproliferative sphingolipid ceramide, to sphingosine, which is a substrate for sphingosine kinases ( 3 ). (aacrjournals.org)
  • Consequently, sphingosine kinases as well as S1P itself have evolved as potential therapeutic targets ( 4-6 ). (aacrjournals.org)
  • BACKGROUND AND PURPOSE: Sphingosine kinases (SK) catalyse the formation of sphingosine 1-phosphate, which is a key lipid mediator regulating cell responses such as proliferation, survival and migration. (biomedsearch.com)
  • This shorter long chain base is considerably less hydrophobic which could significantly change the process of signal transduction.2 Lysosphingolipids (such as sphingosine) inhibit protein kinase C activity resulting in the pathogenesis of sphingolipidoses such as Krabbe's disease and Gaucher's disease but short-chain C12-sphingosine does not demonstrate this inhibitory action.3 Sphingosine can be phosphorylated via two kinases to form sphingosine-1-phosphate, which has important signaling functions. (matreya.com)
  • Lysosphingolipids (sphingolipids containing a free amine on carbon 3) inhibit protein kinase C activity resulting in the pathogenesis of sphingolipidoses such as Krabbe's disease and Gaucher's disease.3 Sphingosine can be phosphorylated via two kinases to form sphingosine-1-phosphate, which has important signaling functions. (matreya.com)
  • Sphingosine kinase (SphK) is a conserved lipid kinase that catalyzes formation sphingosine-1-phosphate (S1P) from the precursor sphingolipid sphingosine. (wikipedia.org)
  • S1P is generated via phosphorylation of the amino alcohol sphingosine catalysed by sphingosine kinase (SphK), which exists in two isoforms: SphK1 and SphK2. (els.net)
  • Sphingosine kinase (SphK) is a highly conserved lipid kinase that phosphorylates sphingosine to form sphingosine-1-phosphate (S1P). (nih.gov)
  • Sphingosine kinase (SphK) 1 and 2 phosphorylate sphingosine to generate sphingosine-1-phosphate (S1P), a pluripotent lipophilic mediator implicated in a variety of cellular events. (jneurosci.org)
  • We concluded: i) initial SphK inhibitors based on sphingosine have low specificity with several important off-targets. (spandidos-publications.com)
  • We have recently demonstrated that BM-MSCs are also able to produce S1P through sphingosine kinase (SphK) activation and to release it similarly to many other cell types [32]. (thefreelibrary.com)
  • Sphingosine 1-phosphate (S1P) is a bioactive sphingolipid produced by sphingosine kinase (SphK). (ovid.com)
  • Sphingolipid metabolites, such as ceramides, sphingosine and sphingosine-1-phosphate, are lipid signaling molecules involved in diverse cellular processes. (wikipedia.org)
  • Sphingosine is formed via degradation of sphingolipid in the lysosome. (wikipedia.org)
  • The sphingolipid metabolites ceramide (Cer), sphingosine (Sph), and sphingosine-1-phosphate (S1P) play an important role in the regulation of cell proliferation, survival, and cell death. (nih.gov)
  • Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid metabolite involved in many critical cell processes. (hindawi.com)
  • Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid mediator involved in many physiological processes including angiogenesis and immune responses [ 1 , 2 ]. (hindawi.com)
  • Sphingosine can be recycled into sphingolipid pathways by ceramide synthase or it can be phosphorylated by one of two SphKs (SphK1 and SphK2) to form sphingosine-1-phosphate (S1P). (spandidos-publications.com)
  • Sphingosine 1-phosphate (S1P) is a bioactive sphingolipid with well-established effects on angiogenesis, carcinogenesis and immunity. (frontiersin.org)
  • Sphingosine-1-phosphate (S1P) is a sphingolipid metabolite that regulates many cellular and physiological processes, including cell growth, survival, movement, angiogenesis, vascular maturation, immunity, and lymphocyte trafficking ( 4 - 6 ). (sciencemag.org)
  • Sphingosine kinase (SK) is an oncogenic sphingolipid-metabolizing enzyme that catalyzes the formation of the mitogenic second messenger sphingosine-1-phosphate (S1P) at the expense of proapoptotic ceramide. (aspetjournals.org)
  • A potential target for this type of cancer might be sphingosine kinase 1 (SphK1) which phosphorylates sphingosine to form sphingosine-1-phosphate (S1P) because it is a critical regulator of sphingolipid-mediated functions and the SphK1/S1P pathway has been implicated in several important biological functions including inflammation and carcinogenesis. (aacrjournals.org)
  • S1P is a signalling sphingolipid synthesized intracellularly from sphingosine via phosphorylation of its primary hydroxyl group. (europa.eu)
  • Sphingosine 1-phosphate (S1P) is a bioactive sphingolipid metabolite involved in many critical cellular processes including proliferation, survival, and migration, as well as angiogenesis and allergic responses. (aspetjournals.org)
  • Sphingosine-1-phosphate (S1P) is a biologically active sphingolipid that has pleiotropic effects in a variety of cell types including ECs, SMCs, and macrophages, all of which are central to the development of atherosclerosis. (jci.org)
  • For instance, the sphingosine-1-phosphate (S1P) is a circulating bioactive sphingolipid capable of triggering strong intracellular reactions through the family of S1P receptors (S1PRs) spread in several cell types and tissues. (americanelements.com)
  • Studies in Drosophila showed that genetic increase of the levels of the bioactive sphingolipid sphingosine-1-phosphate (S1P) or delivery of 2-acetyl-5-tetrahydroxybutyl imidazole (THI), an S1P lyase inhibitor, suppresses dystrophic muscle degeneration. (biologists.org)
  • Sphingosine 1-phosphate (S1P) is a bioactive sphingolipid that is critically involved in the embryonic development of the cardiovascular and central nervous systems. (unboundmedicine.com)
  • A1 - Brinkmann,Volker, Y1 - 2007/05/22/ PY - 2007/04/20/received PY - 2007/04/20/accepted PY - 2007/6/15/pubmed PY - 2007/9/27/medline PY - 2007/6/15/entrez SP - 84 EP - 105 JF - Pharmacology & therapeutics JO - Pharmacol Ther VL - 115 IS - 1 N2 - Sphingosine 1-phosphate (S1P) is a bioactive sphingolipid that is critically involved in the embryonic development of the cardiovascular and central nervous systems. (unboundmedicine.com)
  • Sphingolipid-derived products such as sphingosine and lysosphingolipids have been shown to exert selective actions on a variety of cell types, including neutrophils. (biochemj.org)
  • Catalyzes the phosphorylation of sphingosine to form sphingosine 1-phosphate (SPP), a lipid mediator with both intra- and extracellular functions. (uniprot.org)
  • SphKs are the only enzymes that catalyze ATP-dependent phosphorylation of sphingosine to S1P. (spandidos-publications.com)
  • NIH 3T3 fibroblasts transfected with either SphK1 or SphK2 showed increased sphingosine 1-phosphate (S1P) production, although cells transfected with SphK1 produced higher levels than cells expressing SphK2. (sciencemag.org)
  • Sphingosine (2-amino-4-trans-octadecene-1,3-diol) is an 18-carbon amino alcohol with an unsaturated hydrocarbon chain, which forms a primary part of sphingolipids, a class of cell membrane lipids that include sphingomyelin, an important phospholipid. (wikipedia.org)
  • The aim of this study was to determine the concentrations of free and total sphinganine and sphingosine in milk (human, cow's, sheep's, goat's, soy's) Sphingolipids were extracted from milk. (srce.hr)
  • Ceramide is the basic unit of sphingolipids and consists of a sphingosine attached to a long-chain fatty acyl group via its amino group. (hindawi.com)
  • Sphingosine and its derivative sphinganine are the major bases of the sphingolipids in mammals. (hmdb.ca)
  • Sphingosine 1-phosphate (S1P) 1 , originally considered to be merely the end metabolite of all sphingolipids, is now under the spotlight with important new roles as a signaling molecule ( Spiegel and Milstien, 2003 ) ( Fig. 1 ). (aspetjournals.org)
  • All sphingolipids contain a sphingoid longchain base (sphingosine) backbone, linked to a fatty acid molecule through an amide bond. (aspetjournals.org)
  • Sphingosine 1-phosphate (S1P) is a bioactive metabolic product of sphingolipids generated by sphingosine kinase. (ahajournals.org)
  • Sphingosine 1-phosphate (S1P)-metabolizing enzymes regulate the level of sphingolipids and have important biological functions. (asm.org)
  • One of the sphingolipids, sphingosine, and its downstream product sphingosine 1-phosphate (S1P), have emerged as the modulators of multiple cellular processes, such as cell growth, survival, differentiation, and migration, and have therapeutic potential. (asm.org)
  • Sphingolipids are composed of a backbone of sphingosine which is derived itself from glycerol. (oxforddictionaries.com)
  • Sphingosine is a characteristic structural unit of many sphingolipids such as ceramides, gangliosides, globosides, sulfatides, sphingomyelin, and others.1 It is most abundant in nervous tissue and cell membranes. (matreya.com)
  • The findings of the present study affirm the potential of sphingolipids including ceramide, S1P, and sphingosine to act, either exposed on cell surface or released in the microenvironment, as DAMPs in the response of tumors to PDT. (omicsonline.org)
  • An S , Zheng Y and Bleu T (2000) Sphingosine 1‐phosphate‐induced cell proliferation, survival, and related signaling events mediated by G protein‐coupled receptors Edg3 and Edg5. (els.net)
  • The present invention relates to novel azetidine derivatives, processes for preparing them, pharmaceutical compositions containing them and their use as pharmaceuticals as modulators of sphingosine-1-phosphate receptors. (freepatentsonline.com)
  • Z. Qu, Bernice L. Y. Cheuk, and Stephen W. K. Cheng, "Differential Expression of Sphingosine-1-Phosphate Receptors in Abdominal Aortic Aneurysms," Mediators of Inflammation , vol. 2012, Article ID 643609, 7 pages, 2012. (hindawi.com)
  • Gilenya (fingolimod), licensed from Mitsubishi Tanabe Pharma Corporation, is the first in a new class of drugs that modulates sphingosine 1-phosphate (S1P) receptors[1],[2]. (wordnik.com)
  • The pleiotropic lipid mediator sphingosine-1-phosphate (S1P) can act intracellularly independently of its cell surface receptors through unknown mechanisms. (sciencemag.org)
  • Activation of sphingosine kinase by a variety of agonists increases intracellular S1P, which in turn can function intracellularly as a second messenger or be secreted out of the cell and act extracellularly by binding to and signaling through S1P receptors in autocrine and/or paracrine manners. (aspetjournals.org)
  • In this review we summarize metabolism of S1P, mechanisms of sphingosine kinase activation, and S1P receptors and their downstream signaling pathways and examine relationships to multiple disease processes. (aspetjournals.org)
  • Sphingosine 1-phosphate (S1P) is a bioactive lipid that interacts with cell-surface receptors to exert different cellular responses. (jneurosci.org)
  • Fingolimod is the first oral disease-modifying therapy approved for relapsing forms of multiple sclerosis (MS). Following phosphorylation in vivo, the active agent, fingolimod phosphate (fingolimod-P), acts as a sphingosine 1-phosphate (S1P) receptor modulator, binding with high affinity to four of the five known S1P receptors (S1P1, S1P3, S1P4 and S1P5). (unboundmedicine.com)
  • 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. (uzh.ch)
  • 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. (uzh.ch)
  • Sphingosine 1-phosphate receptors (S1PRs) are expressed in preadipocytes and message expression declines markedly during adipocyte differentiation. (scirp.org)
  • This work establishes that sphingosine receptors were found to be expressed at the mRNA level in ES cell-derived neurons and primary rat megakaryocytes and reveals an unexpected complexity of FTY720 signalling in these cells. (bl.uk)
  • S1P (sphingosine 1-phosphate) is the ligand for a family of specific G-protein-coupled receptors that regulate a wide variety of important cellular functions, including vascular maturation, angiogenesis, cell growth, survival, cytoskeletal rearrangements and cell motility. (portlandpress.com)
  • Sphingosine-1-phosphate and its receptors may be involved in vascular smooth muscle cell (VSMC) proliferation following vascular injury. (strath.ac.uk)
  • Sphingosine-1-phosphate (S1P) regulates immune cell trafficking upon binding to G-protein-coupled receptors. (csic.es)
  • Sphingosine 1-phosphate (S1P) is a bioactive lysolipid with pleiotropic functions mediated through a family of G proteincoupled receptors, S1P 1,2,3,4,5 . (aspetjournals.org)
  • In this study, we investigated the effect of a sphingosine analog, AAL-R, on the host immunity of dendritic cell (DC) response upon the stimulation of toll-like receptors (TLRs) or a viral infection. (umsystem.edu)
  • Sphingosine 1-phosphate (S1P), a lysophospholipid, has gained relevance to multiple sclerosis through the discovery of FTY720 (fingolimod), recently approved as an oral treatment for relapsing forms of multiple sclerosis. (pnas.org)
  • The actions of FTY720 seem to involve at least two, paradoxically, opposite sphingosine 1-phosphate (S1P) receptor mechanisms operating in the immune system: agonism and functional antagonism. (pnas.org)
  • Fingolimod hydrochloride (FTY720) is a first-in-class, orally active, S1P receptor modulator with a structure closely related to sphingosine. (mdpi.com)
  • In particular, we describe recent preclinical and clinical trials of therapies targeting S1P signaling, including 2-amino-2-propane-1,3-diol hydrochloride (FTY720, fingolimod), S1P receptor agonists, sphingosine kinase inhibitors, and anti-S1P monoclonal antibody. (aspetjournals.org)
  • 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. (strath.ac.uk)
  • Background and Purpose- FTY720 is a known sphingosine 1-phosphate receptor agonist. (ahajournals.org)
  • Methods- One hundred eleven male rats were randomly assigned to sham-operated and MCAO treated with vehicle, 0.25 mg/kg and 1 mg/kg of FTY720, another selective sphingosine 1-phosphate receptor-1 agonist SEW2871 (5 mg/kg), or 0.25 mg/kg of FTY720 plus a sphingosine 1-phosphate antagonist, VPC23019 (0.5 mg/kg). (ahajournals.org)
  • Conclusions- These data suggest that activation of sphingosine 1-phosphate-1 by FTY720 reduces neuronal death after transient MCAO. (ahajournals.org)
  • For instance, a sphingosine analog, FTY720, is a promising biomedical drug candidate that is currently being tested in phase III clinical trials for the treatment of multiple sclerosis ( 20 ). (asm.org)
  • The sphingosine analogue fingolimod, also designated FTY720, is one of a still very small number of drugs readily diffusing into the brain and extensively used in humans following its approval for the treatment of multiple sclerosis. (bl.uk)
  • The sphingosine-1-phosphate receptor agonist FTY720 and FTY720-P have a wide variety of fundamental functions. (spandidos-publications.com)
  • This leads to the formation of sphingosine-1-phosphate, a potent signaling lipid. (wikipedia.org)
  • Sphingosine 1-phosphate stimulates TRAF2 E3 ubiquitin ligase activity, and promotes activation of NF-kappa-B in response to TNF signaling. (uniprot.org)
  • May play a role in attenuating intracellular sphingosine 1-phosphate (S1P) signaling. (hmdb.ca)
  • Rosen, H . Sphingosine-1-Phosphate Signaling in Immunology and Infectious Diseases. (uzh.ch)
  • Spiegel, S. and Milstien, S. (2000) Sphingosine-1-phosphate Signaling inside and out. (scirp.org)
  • This is a novel approach to the investigation of the neurovascular unit prompted by the discovery of a drug that influences sphingosine signaling and has been found to be effective in multiple sclerosis. (fondationleducq.org)
  • The protein kinase C (PKC) inhibitors H7 and staurosporine did not induce apoptosis in either cell line, suggesting that PKC-independent signaling is involved in apoptosis induced by sphingosine and DMS, although both sphingosine and DMS have been shown to down-regulate PKC. (aacrjournals.org)
  • Ceramide is broken down by ceramidases to sphingosine, which in turn is phosphorylated by one of two SphKs, SphK1 and SphK2, to generate S1P [ 12 ]. (hindawi.com)
  • Since the discovery that S1P is produced intracellularly by two closely related sphingosine kinase isoenzymes, SphK1 and SphK2, much has been learned about SphK1 and its functions, yet those of SphK2 remain enigmatic ( 7 ). (sciencemag.org)
  • The sphingosine kinase isozymes (SPHK1 and SPHK2) share significant homology but localize to different subcellular compartments and appear to have nonredundant biologic functions ( 7, 8 ). (aacrjournals.org)
  • Use of D-erythro-sphingosine as a pharmacological inhibitor of protein kinase C in human platelets. (abcam.com)
  • Zusätzlich bieten wir Ihnen Sphingosine Kinase 1 Kits (16) und Sphingosine Kinase 1 Proteine (14) und viele weitere Produktgruppen zu diesem Protein an. (antikoerper-online.de)
  • D-erythro-Sphingosine is used to inhibits protein kinase C and calmodulin-dependent enzymes, induces apoptosis. (fishersci.ca)
  • Using a combination of genetic approaches, organotypic cultures of embryonic pancreata, and genomics, we found that sphingosine-1-phosphate (S1p), signalling through the G protein coupled receptor (GPCR) S1pr2, plays a key role in pancreas development linking lineage allocation and specification. (sigmaaldrich.com)
  • S1PR2 encodes the protein known as Sphingosine-1-phosphate receptor 2 (S1P2), a Gprotein-coupled receptor which belongs to a sphingosine-1-phosphate receptor subfamily comprising five members (S1PR1-5). (cellsciences.com)
  • It acts as a functional antagonist on the G protein-coupled receptor sphingosine 1-phosphate receptor 1 (S1P1R) thereby preventing the exit of lymphocytes from lymph nodes. (bl.uk)
  • report that sphingosine kinase 2 (SphK2), despite its sequence similarity to SphK1, promotes apoptosis instead of promoting proliferation as SphK1 does. (sciencemag.org)
  • ABC294640 is a SphK2 selective inhibitor (IC 50 60μM), while ABC294735 (IC 50 SphK1 6μM, IC 50 SphK2 10μM) and SKI-II (IC 50 SphK1 2μM, IC 50 SphK2 1μM) are dual inhibitors in the presence of 10μM sphingosine as substrate. (aacrjournals.org)
  • Sphingosine kinase 2 (SphK2), one of the isoenzymes that generates S1P, was associated with histone H3 and produced S1P that regulated histone acetylation. (sciencemag.org)
  • In human MCF-7 breast cancer cells, SphK2 is predominantly localized to the nucleus ( 10 ), where it is enzymatically active and can produce S1P from sphingosine ( Fig. 1A ). (sciencemag.org)
  • The nucleus contained high amounts of sphingosine (table S1), and SphK2 expression significantly increased nuclear abundance of S1P by sixfold and dihydro-S1P, which lacks the trans double bond at the 4 position, by twofold ( Fig. 1A ). (sciencemag.org)
  • Sphingosine kinase 2 (Sphk2) regulates platelet biogenesis by providing intracellular sphingosine 1-phosphate (S1P). (harvard.edu)
  • Sphingosine-1-phosphate metabolism: can its enigmatic lyase promote the autophagy of fibrosis? (bmj.com)
  • The level of S1P is tightly regulated by the S1P-metabolizing enzymes sphingosine kinase (SK) and S1P lyase (SPL). (asm.org)
  • In 7 families with SRNS and facultative ichthyosis, adrenal insufficiency, immunodeficiency, and neurological defects, we identified 9 different recessive mutations in SGPL1, which encodes sphingosine-1-phosphate (S1P) lyase. (ovid.com)
  • Regulation of cell death by sphingosine 1-phosphate lyase. (inserm.fr)
  • By controlling sphingosine 1-phosphate (S1P) catabolism, S1P lyase (SPL) represents an undeniable candidate as potential regulator of a cancer cell's fate in response to stress. (inserm.fr)
  • Sphingosine kinase, sphingosine-1-phosphate, and apoptosis. (nih.gov)
  • Whereas ceramide and sphingosine are associated with cellular growth arrest and apoptosis, S1P is associated with cellular survival and suppression of apoptosis [ 11 ]. (hindawi.com)
  • Here, we evaluate the effect of d-erythro-N,N-dimethylsphingosine (DMS), a sphingosine kinase (SK) inhibitor, on VSMC proliferation, apoptosis and neointimal formation. (strath.ac.uk)
  • While sphingosines and ceramides can induce apoptosis,4 sphingosine-1-phosphate can promote cell survival or proliferation. (matreya.com)
  • In vitro and in vivo induction of apoptosis by sphingosine and N, N-dimethylsphingosine in human epidermoid carcinoma KB-3-1 and its multidrug-resistant cells. (aacrjournals.org)
  • On the other hand, 15 microM sphingosine or its methylated derivative N, N-dimethylsphingosine (DMS) induced apoptosis in both cell types in vitro. (aacrjournals.org)
  • These results suggested that KB-C2 MDR cells were resistant to apoptosis induction by ADM but sensitive to that by sphingosine and DMS. (aacrjournals.org)
  • Ceramide and sphingosine-1-phosphate, the initial metabolites of sphingosine, failed to induce apoptosis under the same experimental condition as sphingosine/DMS. (aacrjournals.org)
  • Because sphingosine and DMS induce apoptosis regardless of P-glycoprotein expression, they may provide a new strategy and a promising approach to the treatment of anticancer drug-resistant cancer. (aacrjournals.org)
  • Here, we present the crystal structures of human SphK1 in the apo form and in complexes with a substrate sphingosine-like lipid, ADP, and an inhibitor at 2.0-2.3 Å resolution. (rcsb.org)
  • Sphingosine kinase inhibitor (SKI) II (Sigma-Aldrich), SKI V (Sigma-Aldrich), N , N -dimethylsphingosine (DMS) (Cayman Chemical), β-secretase inhibitor IV (Calbiochem), S1P (Calbiochem), and 2-acetyl-4-tetrahydroxybutylimidazole (THI) (Matreya) were purchased from the indicated vendors. (jneurosci.org)
  • Fingolimod is a sphingosine 1-phosphate inhibitor that works by depriving naive and central memory T-cells of a signal to egress from secondary lymph organs. (thefreedictionary.com)
  • Tani, Tabuchi, Hara: Hair Cell Loss Induced by Sphingosine and a Sphingosine Kinase Inhibitor in the Rat Cochlea. (antikoerper-online.de)
  • The sphingosine kinase 2 inhibitor ABC294640 is undergoing clinical testing in cancer patients, and in this study we investigated the effects this first-in-class inhibitor in castration-resistant prostate cancer. (aacrjournals.org)
  • In summary, our results suggest that ABC294640 may reduce the proliferative capacity of castration-resistant prostate cancer cells through inhibition of both sphingosine kinase 2 and dihydroceramide desaturase, thereby providing a foundation for future exploration of this small-molecule inhibitor for the treatment of advanced disease. (aacrjournals.org)
  • Sphingosine-1-phosphate (S1P) is a lipid mediator that controls cell trafficking and activation. (mdpi.com)
  • Recently, sphingosine-1-phosphate (S1P) has emerged as a mediator of angiogenesis, and S1P-induced NO synthesis in endothelial cells (ECs) has been reported. (ahajournals.org)
  • Recently, sphingosine-1-phosphate (S1P), a bioactive lipid released by activated platelets, has emerged as an important mediator of angiogenesis. (ahajournals.org)
  • The results clearly show that both the sphingosine and fatty-acyl groups of liver c16 ceramide were mostly derived from DNL, whereas those of muscle c18 ceramide were derived from non-DNL sources, presumably dietary lipids. (wordnik.com)
  • 1 Recently, an important role for bioactive lipids such as sphingosine-1-phosphate (S1P) and lysophosphatidic acid (LPA), which have a diverse range of cellular functions including proliferation, cell death, adhesion and migration, has emerged. (bmj.com)
  • In addition, neither synthetic sphingosine nor psychosine affected either the formation or metabolism of leukotriene B4. (biochemj.org)
  • Pancreas lineage allocation and specification are regulated by sphingosine-1-phosphate signalling. (sigmaaldrich.com)
  • Sphingosine kinase expression increases intracellular sphingosine -1-phosphate and promotes cell growth and survival. (thefreedictionary.com)
  • Biotinylated sphingosine 1-phosphate (Biotin S1P) is produced by the phosphorylation of biotinyl sphingosine by recombinant human sphingosine kinase 1 and 2 (hSK1 and hSK2). (sigmaaldrich.com)
  • It is, in principle, possible that sphingosine could be involved in the regulation of gene expression and signal transduction. (oxforddictionaries.com)
  • Drought-induced guard cell signal transduction involves sphingosine-1-phosphate. (lancs.ac.uk)
  • We show that after drought treatment sphingosine-1-phosphate levels increase, and we present evidence that this molecule is involved in the signal-transduction pathway linking the perception of abscisic acid to reductions in guard cell turgor. (lancs.ac.uk)
  • The contribution of DNL-derived FA to ceramide synthesis was evaluated based on deuterium labeling of sphingosine - and acyl-groups (D), whereas non-DNL derived FA is illustrated with a blue column on the bottom of each bar. (wordnik.com)
  • Both S1P and LPA are increased within the bronchoalveolar lavage fluid of patients with IPF 2 , 3 and levels of sphingosine kinase1/2 (SPK1/2), which catalyses the synthesis of S1P from sphingosine, correlate negatively with survival in patients with IPF, 4 highlighting an important role in disease. (bmj.com)
  • Its synthesis from sphingosine is catalyzed by SK, while SPL catalyzes the degradation of S1P to phosphoethanolamine and hexadecanal ( 46 ). (asm.org)
  • Western Blot: Sphingosine 1 phosphate phosphatase 2 Antibody [NBP1-53181] - Titration: 2.5ug/ml Positive Control: HepG2 cell lysate. (novusbio.com)
  • Immunohistochemistry-Paraffin: Sphingosine 1 phosphate phosphatase 2 Antibody [NBP1-53181] - Human kidney Tissue, antibody concentration 4-8ug/ml. (novusbio.com)
  • which is mediated by the enzyme sphingosine-1-phosphate phosphatase 2. (hmdb.ca)
  • Fingolimod is in a class of medications called sphingosine l-phosphate receptor modulators. (thefreedictionary.com)
  • Studies of the last two decades have clearly established that sphingosine 1‐phosphate (S1P), considered for many years a mere by‐product of the membrane phospholipid sphingomyelin catabolism, serves indeed as powerful signalling molecule. (els.net)
  • We identified sphingosine-1-phosphate receptor 2 (S1PR2) as a sex- and strain-specific, disease-modifying molecule that regulates BBB permeability by destabilizing adherens junctions. (jci.org)
  • The report assesses the active Sphingosine 1-Phosphate (S1P) Receptor Agonist pipeline products by developmental stage, product type, molecule type, and administration route. (researchandmarkets.com)
  • Thus, sphingosine is considered to be a sphingoid base lipid molecule. (hmdb.ca)
  • Sphingosine is a very hydrophobic molecule, practically insoluble (in water), and relatively neutral. (hmdb.ca)
  • More recently the effects of the signalling molecule sphingosine-1-phosphate (S1P) on the endothelium have been studied [5]. (europa.eu)
  • Here we report that sphingosine-1-phosphate is a new calcium-mobilizing molecule in plants. (lancs.ac.uk)
  • One of the most attractive sites of intervention in this pathway is the conversion of sphingosine to sphingosine-1-phosphate (S1P) by the enzyme sphingosine kinase (SK) ( Spiegel and Milstien, 2003 ). (aspetjournals.org)
  • In particular, sphingosine can be converted into sphingosine 1-phosphate through its interaction with the enzyme sphingosine kinase 2. (hmdb.ca)
  • Ceramide, either synthesised de novo or formed by sphingomyelin catabolism, is the precursor of sphingosine, released by ceramidase‐dependent deacylation. (els.net)
  • or finally broken down by a ceramidase to form sphingosine ( 2 ). (spandidos-publications.com)
  • The data show that transcriptional up-regulation of the sphingosine kinase gene ( SPHK1 ) is a recurrent event associated with the tumorigenic phenotype of these transgenic proerythroblasts. (bloodjournal.org)
  • The transatlantic network led by Christer Betsholtz and Timothy Hla brings together experts in blood vessels, immunology and nervous system function to focus on the central role of sphingosine 1-phosphate (S1P) in the development and regulation of the neurovascular unit and blood brain barrier (BBB) in health and disease. (fondationleducq.org)
  • Here we show that torpor induces the storage of lymphocytes in secondary lymphoid organs in response to a temperature-dependent drop in plasma levels of sphingosine-1-phosphate (S1P). (rug.nl)
  • However, levels of sphingosine-1-phosphate (S1P) were significantly increased in Ormdl3 Δ2-3/Δ2-3 /CC10 mice as well as in airway epithelial cells in which ORMDL3 was inhibited with small interfering RNA. (jimmunol.org)
  • 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 capacity to act as danger-associated molecular patterns (DAMPs). (omicsonline.org)
  • The most frequent long-chain bases in most of the mammals are D-erythro-sphinganine and sphingosine. (srce.hr)
  • Analysis of tissues for sphinganine and sphingosine is not readily available. (oxforddictionaries.com)
  • Sphingosine analogs display immune suppressive activities and thus have therapeutic potential in the treatment of autoimmune diseases. (umsystem.edu)
  • In this study, we focused on a biologically active lipid metabolite, sphingosine-1-phosphate (S1P). (jneurosci.org)
  • Sphingosine may be a unique E. coli metabolite. (hmdb.ca)
  • Molecular fragments and ions of acyl - and sphingosine groups in TMS-derivatized ceramides (A) and their mass spectra (B). (wordnik.com)
  • Professor of biochemistry and associate director of the Institute for Stem Cell and Regenerative Medicine, Hannele Ruohola-Baker's lab originally identified the sphingosine 1-phosphate (S1P) pathway as a critical player in ameliorating muscular dystrophy in flies. (thefreedictionary.com)
  • We searched for novel autophagic pathways in primary neurons and identified the cytosolic sphingosine-1-phosphate (S1P) pathway as a regulator of neuronal autophagy. (rice.edu)
  • eEF1A1 is known to stimulate the proangiogenic sphingosine pathway that is located and activated around endothelial caveolae. (ahajournals.org)
  • Sphingosine kinase 1 (SphK1) is a lipid kinase that catalyzes the conversion of sphingosine to sphingosine-1-phosphate (S1P), which has been shown to play a role in lymphocyte trafficking, angiogenesis, and response to apoptotic stimuli. (rcsb.org)
  • Are more sphingosine 1-phosphate receptor agonists a better therapeutic option against multiple sclerosis? (bmj.com)
  • D-erythro-C12-sphingosine is a shortchain analog of natural sphingosine that exhibits different cellular effects from the long-chain sphingosines. (matreya.com)
  • Due to its natural stereochemistry and very similar physical characteristics to natural sphingosines this product represents the extraction and signal intensity of natural sphingosine in most applications making it a useful choice as an internal standard. (matreya.com)
  • This synthetic sphingosine contains an odd number of carbons with a natural D-erythro stereocenter making it an ideal internal standard for sphingolipidomic studies using HPLC and mass spectrometry. (matreya.com)
  • Wada A, Igarashi Y (2002) N-glycans of sphingosine 1-phosphate receptor Edg-1 regulate ligand-induced receptor internalization. (wordnik.com)
  • This inhibition results in accumulated sphingosine and sphingamine in serum, urine and tissues, and reduces the biosynthesis of sphingomyelin. (thefreedictionary.com)
  • Sphingosine 1-Phosphate (S1P) Receptor Agonist - Pipeline Insight, 2019" report offers comprehensive insights of the pipeline (under development) therapeutics scenario and growth prospects across "Sphingosine 1-Phosphate (S1P) Receptor Agonist development. (researchandmarkets.com)
  • Descriptive coverage of pipeline development activities for "Sphingosine 1-Phosphate (S1P) Receptor Agonist - Pipeline therapeutics development coverage provides descriptive product profiles including (but not limited to) drug description, product development and R&D activities encompassing clinical and pre-clinical studies, designations, collaborations, licensing deals, grants, technologies and patent details. (researchandmarkets.com)
  • Sphingosine, also known as (4E)-sphingenine or sphing-4-enine, belongs to the class of organic compounds known as 1,2-aminoalcohols. (hmdb.ca)
  • While no release of S1P was detected, elevated levels of its precursor sphingosine were found in the supernatants of PDT-treated cells. (omicsonline.org)
  • Sphingosine kinase 1 enables communication between melanoma cells and fibroblasts that provides a new link to metastasis. (thefreedictionary.com)
  • Billich, Urtz, Reuschel, Baumruker: Sphingosine kinase 1 is essential for proteinase-activated receptor-1 signalling in epithelial and endothelial cells. (antikoerper-online.de)
  • In contrast to that of SPL, the overexpression of S1P-producing sphingosine kinase 1 heightened the cells' susceptibility to influenza virus infection, an effect that was reversed by the inhibition of its kinase activity, representing opposed enzymatic activity. (asm.org)
  • Sphingosine 1-Phosphate Receptor 1 Is Required for MMP-2 Function in Bone Marrow Mesenchymal Stromal Cells: Implications for Cytoskeleton Assembly and Proliferation. (thefreelibrary.com)
  • In contrast, the increase of SM content in MEB4 cells to 6% by the addition of sphingosine did not affect the viability of the cells. (oxforddictionaries.com)
  • Loss of sphingosine kinase-1 in carcinoma cells increases formation of reactive oxygen species and sensitivity to doxorubicin-induced DNA damage. (biomedsearch.com)
  • Sphingosine has been shown to cause an increase in the cytoplasmic calcium level of cells. (matreya.com)
  • Mammalian cells contain mostly Derythro sphingosines having C18 and C20 bases with a smaller amount of C16 bases. (matreya.com)
  • Accurate quantification of sphingosine-1-phosphate in normal and Fabry disease plasma, cells and tissues by LC-MS/MS with (13)C-encoded natural S1P as internal standard. (leidenuniv.nl)
  • Altogether, these data suggest that overexpression of the sphingosine kinase may represent an oncogenic event during the multistep progression of an erythroleukemia. (bloodjournal.org)
  • The sphingosine 1-phosphate receptor 1 (S1P 1 ) and its ligand, sphingosine 1-phosphate (S1P), have now emerged as critical regulators of lymphocyte trafficking, vascular development and integrity, and immunity. (sciencemag.org)