8-11-14-eicosatrienoic-acid has been researched along with 5-hydroxy-6-8-11-14-eicosatetraenoic-acid* in 9 studies
9 other study(ies) available for 8-11-14-eicosatrienoic-acid and 5-hydroxy-6-8-11-14-eicosatetraenoic-acid
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Epoxyeicosatrienoic acid agonist regulates human mesenchymal stem cell-derived adipocytes through activation of HO-1-pAKT signaling and a decrease in PPARγ.
Human mesenchymal stem cells (MSCs) expressed substantial levels of CYP2J2, a major CYP450 involved in epoxyeicosatrienoic acid (EET) formation. MSCs synthesized significant levels of EETs (65.8 ± 5.8 pg/mg protein) and dihydroxyeicosatrienoic acids (DHETs) (15.83 ± 1.62 pg/mg protein), suggesting the presence of soluble epoxide hydrolase (sEH). The addition of an sEH inhibitor to MSC culture decreased adipogenesis. EETs decreased MSC-derived adipocytes in a concentration-dependent manner, 8,9- and 14,15-EET having the maximum reductive effect on adipogenesis. We examined the effect of 12-(3-hexylureido)dodec-8(Z)-enoic acid, an EET agonist, on MSC-derived adipocytes and demonstrated an increased number of healthy small adipocytes, attenuated fatty acid synthase (FAS) levels (P < 0.01), and reduced PPARγ, C/EBPα, FAS, and lipid accumulation (P < 0.05). These effects were accompanied by increased levels of heme oxygenase (HO)-1 and adiponectin (P < 0.05), and increased glucose uptake (P < 0.05). Inhibition of HO activity or AKT by tin mesoporphyrin (SnMP) and LY2940002, respectively, reversed EET-induced inhibition of adipogenesis, suggesting that activation of the HO-1-adiponectin axis underlies EET effect in MSCs. These findings indicate that EETs decrease MSC-derived adipocyte stem cell differentiation by upregulation of HO-1-adiponectin-AKT signaling and play essential roles in the regulation of adipocyte differentiation by inhibiting PPARγ, C/EBPα, and FAS and in stem cell development. These novel observations highlight the seminal role of arachidonic acid metabolism in MSCs and suggest that an EET agonist may have potential therapeutic use in the treatment of dyslipidemia, diabetes, and the metabolic syndrome. Topics: 8,11,14-Eicosatrienoic Acid; Adipocytes; Adipogenesis; Adiponectin; Arachidonic Acid; CCAAT-Enhancer-Binding Proteins; Chromones; Cytochrome P-450 CYP2J2; Cytochrome P-450 Enzyme System; Epoxide Hydrolases; Fatty Acid Synthases; Fatty Acids, Monounsaturated; Glucose; Heme Oxygenase-1; Humans; Hydroxyeicosatetraenoic Acids; Lipids; Mesenchymal Stem Cells; Metalloporphyrins; Morpholines; PPAR gamma; Proto-Oncogene Proteins c-akt; Signal Transduction | 2010 |
L-4F differentially alters plasma levels of oxidized fatty acids resulting in more anti-inflammatory HDL in mice.
To determine in vivo if L-4F differentially alters plasma levels of oxidized fatty acids resulting in more anti-inflammatory HDL. Injecting L-4F into apoE null mice resulted in a significant reduction in plasma levels of 15-HETE, 5-HETE, 13-HODE and 9-HODE. In contrast, plasma levels of 20-HETE were not reduced and plasma levels of 14,15-EET, which are derived from the cytochrome P450 pathway, were elevated after injection of L-4F. Injection of 13(S)-HPODE into wild-type C57BL/6J mice caused an increase in plasma levels of 13-HODE and 9-HODE and was accompanied by a significant loss in the anti-inflammatory properties of HDL. The response of atherosclerosis resistant C3H/HeJ mice to injection of 13(S)-HPODE was similar but much more blunted. Injection of L-4F at a site different from that at which the 13(S)-HPODE was injected resulted in significantly lower plasma levels of 13-HODE and 9-HODE and significantly less loss of HDL anti-inflammatory properties in both strains. i) L-4F differentially alters plasma levels of oxidized fatty acids in vivo. ii) The resistance of the C3H/HeJ strain to atherosclerosis may in part be mediated by a reduced reaction of this strain to these potent lipid oxidants. Topics: 8,11,14-Eicosatrienoic Acid; Animals; Anti-Inflammatory Agents; Apolipoproteins E; Atherosclerosis; Chromatography, Liquid; Enzyme-Linked Immunosorbent Assay; Fatty Acids; Female; Hydroxyeicosatetraenoic Acids; Injections, Subcutaneous; Linoleic Acids; Linoleic Acids, Conjugated; Lipid Peroxides; Lipoproteins, HDL; Mice; Mice, Inbred C3H; Mice, Inbred C57BL; Mice, Knockout; Oxidation-Reduction; Peptides; Species Specificity; Tandem Mass Spectrometry; Time Factors; Up-Regulation | 2010 |
Dietary (n-9) eicosatrienoic acid from a cultured fungus inhibits leukotriene B4 synthesis in rats and the effect is modified by dietary linoleic acid.
Eicosatrienoic acid (ETrA) is the (n-9) homologue of (n-6) arachidonic acid (AA) and (n-3) eicosapentaenoic acid (EPA). ETrA can be synthesized endogeneously, but tissue levels are normally undetectable except in essential fatty acid (EFA) deficiency. An ETrA-rich oil extracted from a cultured fungus was used to prepare diets which had varying levels of ETrA (0-8 g/kg diet) in combination with one of two levels of linoleic acid (LA, 2.2 or 9.5 g/kg diet). All diets were sufficient in essential fatty acids. Groups of rats were fed these diets for 4 wk after which leucocyte fatty acid content and leukotriene B4 (LTB4) synthesis were measured. The influence of dietary LA on ETrA accumulation in cells was studied and correlations with LTB4 synthesis determined. ETrA was efficiently incorporated into peritoneal exudate cell (PEC) phospholipids with no evident saturation being observed with levels up to 10 mol/100 mol total fatty acids in peritoneal exudate cells. Cellular ETrA levels were lower (P < 0.001) in rats fed the higher level of LA. ETrA accumulation in peritoneal exudate cells correlated (r(2) = 0.63, P < 0.05) with reduced LTB4 synthesis which was attributable to LTA hydrolase inhibition. Thus, dietary ETrA from a biological source can accumulate in leucocytes and suppress inflammatory eicosanoid synthesis. The findings justify further studies into the biochemical and anti-inflammatory effects of dietary ETrA, which could be incorporated into palatable food additives. Topics: 8,11,14-Eicosatrienoic Acid; Animals; Arachidonate 5-Lipoxygenase; Ascitic Fluid; Dietary Fats, Unsaturated; Female; Hydroxyeicosatetraenoic Acids; Leukotriene B4; Linoleic Acid; Linoleic Acids; Mucorales; Phospholipids; Rats | 1996 |
[A comparison of the effects of 5-hydroxyeicosatetraenoic acid and hepoxilin A3 on the plasticity of the snail neuronal cholinoreceptors].
The effects of two acyclic derivatives of arachidonic acid which are formed under the action of 5- and 12-lipoxygenases 5(S)-hydroxy-(6,8Z,11Z,14Z)-eicosatetraenoic acid (5-HETE) and (8R/S)-hydroxy-(11S,12S)-epoxy-5Z,9E,14Z-eicosatrienoi c acid (hepoxilin A3) on extinction of inward current evoked by local acetylcholine (ACh-current) application on soma of Helix lucorum RPa3 and LPa3 neurons were studied by the double-electrode voltage clamp technique. It was shown an increase in ACh-current extinction by 5-HETE. Hepoxilin A3 did not influence cholinoreceptor plasticity. The present results confirm earlier assumptions concerning the regulation of cholinoreceptor plasticity by acyclic eicosanoids which were formed from arachidonic acid under the influence of 5-lipoxygenase and the lack of 12-lipoxygenase metabolites in this regulation. Topics: 8,11,14-Eicosatrienoic Acid; Acetylcholine; Animals; Helix, Snails; Hydroxyeicosatetraenoic Acids; In Vitro Techniques; Membrane Potentials; Microelectrodes; Neuronal Plasticity; Neurons; Receptors, Cholinergic | 1993 |
5,6-Epoxyeicosatrienoic acid stimulates growth hormone release in rat anterior pituitary cells.
The effect of arachidonic acid and some of its metabolites have been examined in rat anterior pituitary cells for their ability to release growth hormone. The cytochrome P-450 metabolite, 5,6-epoxyeicosatrienoic acid is a much more effective growth-hormone releasing agent than 15-hydroxyeicosatetraenoic acid, 15-hydroxyeicosatetraenoic acid methyl ester, 5-hydroxyeicosatetraenoic acid or arachidonic acid. The release of growth hormone is rapid, dose-dependent and reaches an apparent saturation after eight minutes. These studies described herein provide evidence that lipoxygenase and cyclooxygenase products of arachidonic acid are less potent while cytochrome P-450 products are more potent in the release of growth hormone from anterior pituitary cells. Topics: 8,11,14-Eicosatrienoic Acid; Animals; Arachidonic Acids; Cells, Cultured; Fatty Acids, Unsaturated; Female; Growth Hormone; Hydroxyeicosatetraenoic Acids; Kinetics; Pituitary Gland, Anterior; Rats; Rats, Inbred F344 | 1989 |
Ability of 15-hydroxyeicosatrienoic acid (15-OH-20:3) to modulate macrophage arachidonic acid metabolism.
Mouse peritoneal macrophages metabolize dihomogammalinolenic acid (20:3n-6) primarily to 15-hydroxy-8,11,13-eicosatrienoic acid (15-OH-20:3). Since the biological properties of this novel trienoic eicosanoid remain poorly defined, the effects of increasing concentrations of 15-OH-20:3 and its arachidonic acid (20:4n-6) derived analogue. 15-hydroxy-5,8,11,13-eicosatetraenoic acid (15-HETE), on mouse macrophage 20:4n-6 metabolism were investigated. Resident peritoneal macrophages were prelabeled with [3H]-20:4n-6 and subsequently stimulated with zymosan in the presence of either 15-OH-20:3 or 15-HETE (1-30 microM). After 1 hr, the radiolabeled soluble metabolites were analyzed by reverse phase high performance liquid chromatography. 15-OH-20:3 inhibited zymosan-induced leukotriene C4 (IC50 = 2.4 microM) and 5-HETE (IC50 = 3.1 microM) synthesis. In contrast to the inhibition of macrophage 5-lipoxygenase, 15-OH-20:3 enhanced 12-HETE synthesis (5-30 microM) and had no measurable effect on cyclooxygenase metabolism (1-10 microM) i.e., 6-keto-prostaglandin F1 alpha and prostaglandin E2 synthesis. Addition of exogenous 15-HETE produced similar effects. These results suggest that the manipulation of macrophage 15-OH-20:3n-6 levels may provide a measure of cellular control over 20:4n-6 metabolism, specifically, leukotriene production. Topics: 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; 8,11,14-Eicosatrienoic Acid; Animals; Arachidonic Acid; Arachidonic Acids; Fatty Acids, Unsaturated; Hydroxy Acids; Hydroxyeicosatetraenoic Acids; Macrophages; Mice; SRS-A | 1988 |
Preferential incorporation of eicosanoid precursor fatty acids into human umbilical vein endothelial cell phospholipids.
We have examined the preferential incorporation of specific fatty acids into phospholipid classes of cultured human umbilical vein endothelial cells. Pulse-labeling of human umbilical vein endothelial cell phospholipids with radiolabeled fatty acids and inhibition of radiolabeled fatty acid incorporation by competition with excess, unlabeled fatty acids in pair-wise combinations revealed two distinct classes of esterification systems into human umbilical vein endothelial cell phospholipids. The eicosanoid precursor fatty acids, including arachidonate, 8,11,14-eicosatrienoate (ETA) and 5,8,11,14,17-eicosapentaenoate (EPA), exhibited high affinity incorporation into total phospholipids, whereas other fatty acids, including docosahexaenoate and monohydroxy eicosatetraenoates, showed low affinity incorporation. The relative degree of incorporation of eicosanoid precursor fatty acids into phospholipid classes was phosphatidylcholine (PC) greater than phosphatidylethanolamine (PE) greater than phosphatidylinositol (PI) greater than phosphatidylserine (PS). The specific activity of [14C]arachidonic acid-labeled PI was two times higher than that of any other radiolabeled phospholipids. When competitive incorporation of eicosanoid precursor fatty acids into phospholipid classes was studied, they were found to be acylated into different phospholipid classes at different rates. Although eicosanoid precursor fatty acids were not preferentially incorporated into PC, arachidonic acid was preferentially incorporated into the other phospholipids and exhibited particular selectivity in comparison with the other eicosanoid precursor fatty acids for incorporation into PI. These results demonstrate that human umbilical vein endothelial cells possess selective incorporation mechanisms for specific fatty acids into various phospholipids via the deacylation-reacylation pathway. Topics: 8,11,14-Eicosatrienoic Acid; Docosahexaenoic Acids; Eicosanoic Acids; Eicosapentaenoic Acid; Endothelium, Vascular; Fatty Acids; Humans; Hydroxyeicosatetraenoic Acids; Phospholipids; Umbilical Veins | 1987 |
Epoxy derivatives of arachidonic acid are potent stimulators of prolactin secretion.
Arachidonic acid is metabolized to three distinct classes of metabolites: cyclooxygenase produces prostaglandins, prostacyclins, and thromboxanes; lipoxygenase produces hydroperoxyeicosatetraenoic acids and, epoxygenase, a NADPH-dependent cytochrome P-450 enzyme, produces epoxyeicosatrienoic acids. Addition of 5,6-epoxyeicosatrienoic acid (5,6-EET) to GH3 cells, a rat anterior pituitary cell line, produces a rapid, dose-dependent stimulation of prolactin (PRL) release. Incubation with arachidonic acid (AA) was ineffective at increasing PRL release. The lipoxygenase metabolite 5-hydroxyeicosatetraenoic acid (5-HETE), however, increased PRL release from GH3 cells but with a much lower maximal response than 5,6-EET. We examined the role of metabolism inhibitors in 5,6-EET-mediated PRL release. Microsomal and cytosolic epoxide hydrolase (EH) inhibitors do not alter 5,6-EET-induced PRL release, suggesting that EH does not play a significant role in 5,6-EET mediated PRL release from GH3 cells. A chemical analog of 5,6-EET wherein the epoxide oxygen is replaced with a sulfur to afford 5,6-thioepoxyeicosatrienoic acid was also tested and found to stimulate the release of PRL, although not to the same extent as 5,6-EET. Although 5-HETE tends to increase PRL release from GH3 cells, 5,6-EET is significantly more potent at the stimulation of PRL release from GH3 cells. Topics: 8,11,14-Eicosatrienoic Acid; Animals; Arachidonic Acids; Cell Line; Epoxide Hydrolases; Epoxy Compounds; Hydroxyeicosatetraenoic Acids; Pituitary Gland, Anterior; Prolactin; Rats | 1987 |
An analysis of the relationship between 5-lipoxygenase product generation and the secretion of preformed mediators from mouse bone marrow-derived mast cells.
The quantitative relationships between the secretion of a granule-associated mediator, beta-hexosaminidase, and the oxidative metabolism of arachidonic acid by the 5-lipoxygenase pathway were analyzed for a homogeneous population of T cell-dependent, bone marrow-derived, murine mast cells. The mast cells were either sensitized with a monoclonal IgE and challenged with specific antigen, or to bypass a transmembrane signal, were stimulated with calcium ionophore A23187. The released products of the 5-lipoxygenase pathway were quantitated by integrated ultraviolet absorbance after resolution by reverse phase-high performance liquid chromatography in the case of 5-hydroxy-eicosatetraenoic acid (5-HETE), and by separate radioimmunoassays for leukotriene C4 (LTC4) and leukotriene B4 (LTB4). The activation-release response of the cells was perturbated by the introduction of three pharmacologic agents, each directed to different steps in the 5-lipoxygenase pathway of arachidonic acid metabolism, and the action of each agent was determined for separate cell samples while present and after its removal by washing. 5,6-Dehydroarachidonic acid (5,6-DHA), an irreversible inhibitor of 5-lipoxygenase, prevented formation of 5-HETE from exogenous [14C]arachidonic acid and from membrane-derived arachidonic acid in a dose-related fashion when sensitized mast cells, preincubated with drug, were washed before antigen activation. Release of 5-HETE, LTC4, and LTB4 was inhibited by 5,6-DHA in a corresponding dose-related fashion, with a minimal preincubation period of 1 to 5 min before the cells were washed and subjected to antigen-dependent activation. In contrast, the inhibitory effect of 5,6-DHA on beta-hexosaminidase release was lost after three washes and was not evident after one wash unless the preincubation period was extended to 15 min. The capacity of 5,6-DHA to prevent leukotriene generation without altering beta-hexosaminidase release was also observed with ionophore-activated mast cells. Preincubation of sensitized cells with diethylcarbamazine (DEC), followed by a wash before antigen-dependent activation, produced inhibition of leukotriene generation, no effect on beta-hexosaminidase release, and augmentation of 5-HETE release at the maximum dose studied; thus, DEC interrupts the pathway distal to the formation of 5-hydroperoxy-eicosatetraenoic acid (5-HPETE) from arachidonic acid by 5-lipoxygenase. Preincubation of sensitized cells with incremental amounts of the Topics: 8,11,14-Eicosatrienoic Acid; Animals; Arachidonate Lipoxygenases; Arachidonic Acids; beta-N-Acetylhexosaminidases; Bone Marrow Cells; Diethylcarbamazine; Hexosaminidases; Hydroxyeicosatetraenoic Acids; Immunoglobulin E; Leukotriene B4; Lipoxygenase; Lipoxygenase Inhibitors; Male; Mast Cells; Mice; Mice, Inbred BALB C; SRS-A | 1984 |