Arachidonic Acid: An unsaturated, essential fatty acid. It is found in animal and human fat as well as in the liver, brain, and glandular organs, and is a constituent of animal phosphatides. It is formed by the synthesis from dietary linoleic acid and is a precursor in the biosynthesis of prostaglandins, thromboxanes, and leukotrienes.Arachidonic AcidsPhospholipases A2: Phospholipases that hydrolyze the acyl group attached to the 2-position of PHOSPHOGLYCERIDES.Phospholipases A: Phospholipases that hydrolyze one of the acyl groups of phosphoglycerides or glycerophosphatidates.Hydroxyeicosatetraenoic Acids: Eicosatetraenoic acids substituted in any position by one or more hydroxy groups. They are important intermediates in a series of biosynthetic processes leading from arachidonic acid to a number of biologically active compounds such as prostaglandins, thromboxanes, and leukotrienes.Lipoxygenase: An enzyme of the oxidoreductase class primarily found in PLANTS. It catalyzes reactions between linoleate and other fatty acids and oxygen to form hydroperoxy-fatty acid derivatives.12-Hydroxy-5,8,10,14-eicosatetraenoic Acid: A lipoxygenase metabolite of ARACHIDONIC ACID. It is a highly selective ligand used to label mu-opioid receptors in both membranes and tissue sections. The 12-S-HETE analog has been reported to augment tumor cell metastatic potential through activation of protein kinase C. (J Pharmacol Exp Ther 1995; 274(3):1545-51; J Natl Cancer Inst 1994; 86(15):1145-51)Masoprocol: A potent lipoxygenase inhibitor that interferes with arachidonic acid metabolism. The compound also inhibits formyltetrahydrofolate synthetase, carboxylesterase, and cyclooxygenase to a lesser extent. It also serves as an antioxidant in fats and oils.5,8,11,14-Eicosatetraynoic Acid: A 20-carbon unsaturated fatty acid containing 4 alkyne bonds. It inhibits the enzymatic conversion of arachidonic acid to prostaglandins E(2) and F(2a).8,11,14-Eicosatrienoic Acid: A 20-carbon-chain fatty acid, unsaturated at positions 8, 11, and 14. It differs from arachidonic acid, 5,8,11,14-eicosatetraenoic acid, only at position 5.Lipoxygenase Inhibitors: Compounds that bind to and inhibit that enzymatic activity of LIPOXYGENASES. Included under this category are inhibitors that are specific for lipoxygenase subtypes and act to reduce the production of LEUKOTRIENES.Prostaglandins: A group of compounds derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway. They are extremely potent mediators of a diverse group of physiological processes.Eicosanoids: A class of compounds named after and generally derived from C20 fatty acids (EICOSANOIC ACIDS) that includes PROSTAGLANDINS; LEUKOTRIENES; THROMBOXANES, and HYDROXYEICOSATETRAENOIC ACIDS. They have hormone-like effects mediated by specialized receptors (RECEPTORS, EICOSANOID).Arachidonate Lipoxygenases: Enzymes catalyzing the oxidation of arachidonic acid to hydroperoxyarachidonates. These products are then rapidly converted by a peroxidase to hydroxyeicosatetraenoic acids. The positional specificity of the enzyme reaction varies from tissue to tissue. The final lipoxygenase pathway leads to the leukotrienes. EC 1.13.11.- .Arachidonate 5-Lipoxygenase: An enzyme that catalyzes the oxidation of arachidonic acid to yield 5-hydroperoxyarachidonate (5-HPETE) which is rapidly converted by a peroxidase to 5-hydroxy-6,8,11,14-eicosatetraenoate (5-HETE). The 5-hydroperoxides are preferentially formed in leukocytes.Prostaglandin-Endoperoxide Synthases: Enzyme complexes that catalyze the formation of PROSTAGLANDINS from the appropriate unsaturated FATTY ACIDS, molecular OXYGEN, and a reduced acceptor.Leukotrienes: A family of biologically active compounds derived from arachidonic acid by oxidative metabolism through the 5-lipoxygenase pathway. They participate in host defense reactions and pathophysiological conditions such as immediate hypersensitivity and inflammation. They have potent actions on many essential organs and systems, including the cardiovascular, pulmonary, and central nervous system as well as the gastrointestinal tract and the immune system.Group IV Phospholipases A2: A cytosolic phospholipase A2 group that plays an important role in the release of free ARACHIDONIC ACID, which in turn is metabolized to PROSTAGLANDINS by the CYCLOOXYGENASE pathway and to LEUKOTRIENES by the 5-LIPOXYGENASE pathway.Indomethacin: A non-steroidal anti-inflammatory agent (NSAID) that inhibits the enzyme cyclooxygenase necessary for the formation of prostaglandins and other autacoids. It also inhibits the motility of polymorphonuclear leukocytes.Fatty Acids, Unsaturated: FATTY ACIDS in which the carbon chain contains one or more double or triple carbon-carbon bonds.Quinacrine: An acridine derivative formerly widely used as an antimalarial but superseded by chloroquine in recent years. It has also been used as an anthelmintic and in the treatment of giardiasis and malignant effusions. It is used in cell biological experiments as an inhibitor of phospholipase A2.Dinoprostone: The most common and most biologically active of the mammalian prostaglandins. It exhibits most biological activities characteristic of prostaglandins and has been used extensively as an oxytocic agent. The compound also displays a protective effect on the intestinal mucosa.Calcimycin: An ionophorous, polyether antibiotic from Streptomyces chartreusensis. It binds and transports CALCIUM and other divalent cations across membranes and uncouples oxidative phosphorylation while inhibiting ATPase of rat liver mitochondria. The substance is used mostly as a biochemical tool to study the role of divalent cations in various biological systems.Leukotriene B4: The major metabolite in neutrophil polymorphonuclear leukocytes. It stimulates polymorphonuclear cell function (degranulation, formation of oxygen-centered free radicals, arachidonic acid release, and metabolism). (From Dictionary of Prostaglandins and Related Compounds, 1990)Thromboxane B2: A stable, physiologically active compound formed in vivo from the prostaglandin endoperoxides. It is important in the platelet-release reaction (release of ADP and serotonin).4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine: A dual inhibitor of both cyclooxygenase and lipoxygenase pathways. It exerts an anti-inflammatory effect by inhibiting the formation of prostaglandins and leukotrienes. The drug also enhances pulmonary hypoxic vasoconstriction and has a protective effect after myocardial ischemia.Cyclooxygenase Inhibitors: Compounds or agents that combine with cyclooxygenase (PROSTAGLANDIN-ENDOPEROXIDE SYNTHASES) and thereby prevent its substrate-enzyme combination with arachidonic acid and the formation of eicosanoids, prostaglandins, and thromboxanes.Prostaglandins E: (11 alpha,13E,15S)-11,15-Dihydroxy-9-oxoprost-13-en-1-oic acid (PGE(1)); (5Z,11 alpha,13E,15S)-11,15-dihydroxy-9-oxoprosta-5,13-dien-1-oic acid (PGE(2)); and (5Z,11 alpha,13E,15S,17Z)-11,15-dihydroxy-9-oxoprosta-5,13,17-trien-1-oic acid (PGE(3)). Three of the six naturally occurring prostaglandins. They are considered primary in that no one is derived from another in living organisms. Originally isolated from sheep seminal fluid and vesicles, they are found in many organs and tissues and play a major role in mediating various physiological activities.Arachidonate 12-Lipoxygenase: An enzyme that catalyzes the oxidation of arachidonic acid to yield 12-hydroperoxyarachidonate (12-HPETE) which is itself rapidly converted by a peroxidase to 12-hydroxy-5,8,10,14-eicosatetraenoate (12-HETE). The 12-hydroperoxides are preferentially formed in PLATELETS.Eicosanoic Acids: 20-carbon saturated monocarboxylic acids.Phospholipids: Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides see GLYCEROPHOSPHOLIPIDS) or sphingosine (SPHINGOLIPIDS). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system.Docosahexaenoic Acids: C22-unsaturated fatty acids found predominantly in FISH OILS.Fatty Acids: Organic, monobasic acids derived from hydrocarbons by the equivalent of oxidation of a methyl group to an alcohol, aldehyde, and then acid. Fatty acids are saturated and unsaturated (FATTY ACIDS, UNSATURATED). (Grant & Hackh's Chemical Dictionary, 5th ed)Linoleic Acid: A doubly unsaturated fatty acid, occurring widely in plant glycosides. It is an essential fatty acid in mammalian nutrition and is used in the biosynthesis of prostaglandins and cell membranes. (From Stedman, 26th ed)Cyclooxygenase 2: An inducibly-expressed subtype of prostaglandin-endoperoxide synthase. It plays an important role in many cellular processes and INFLAMMATION. It is the target of COX2 INHIBITORS.Cyclooxygenase 1: A constitutively-expressed subtype of prostaglandin-endoperoxide synthase. It plays an important role in many cellular processes.Eicosapentaenoic Acid: Important polyunsaturated fatty acid found in fish oils. It serves as the precursor for the prostaglandin-3 and thromboxane-3 families. A diet rich in eicosapentaenoic acid lowers serum lipid concentration, reduces incidence of cardiovascular disorders, prevents platelet aggregation, and inhibits arachidonic acid conversion into the thromboxane-2 and prostaglandin-2 families.SRS-A: A group of LEUKOTRIENES; (LTC4; LTD4; and LTE4) that is the major mediator of BRONCHOCONSTRICTION; HYPERSENSITIVITY; and other allergic reactions. Earlier studies described a "slow-reacting substance of ANAPHYLAXIS" released from lung by cobra venom or after anaphylactic shock. The relationship between SRS-A leukotrienes was established by UV which showed the presence of the conjugated triene. (From Merck Index, 11th ed)Epoprostenol: A prostaglandin that is a powerful vasodilator and inhibits platelet aggregation. It is biosynthesized enzymatically from PROSTAGLANDIN ENDOPEROXIDES in human vascular tissue. The sodium salt has been also used to treat primary pulmonary hypertension (HYPERTENSION, PULMONARY).6-Ketoprostaglandin F1 alpha: The physiologically active and stable hydrolysis product of EPOPROSTENOL. Found in nearly all mammalian tissue.Linoleic Acids: Eighteen-carbon essential fatty acids that contain two double bonds.Cytochrome P-450 Enzyme System: A superfamily of hundreds of closely related HEMEPROTEINS found throughout the phylogenetic spectrum, from animals, plants, fungi, to bacteria. They include numerous complex monooxygenases (MIXED FUNCTION OXYGENASES). In animals, these P-450 enzymes serve two major functions: (1) biosynthesis of steroids, fatty acids, and bile acids; (2) metabolism of endogenous and a wide variety of exogenous substrates, such as toxins and drugs (BIOTRANSFORMATION). They are classified, according to their sequence similarities rather than functions, into CYP gene families (>40% homology) and subfamilies (>59% homology). For example, enzymes from the CYP1, CYP2, and CYP3 gene families are responsible for most drug metabolism.Blood Platelets: Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation.Arachidonate 15-Lipoxygenase: An enzyme that catalyzes the oxidation of arachidonic acid to yield 15-hydroperoxyarachidonate (15-HPETE) which is rapidly converted to 15-hydroxy-5,8,11,13-eicosatetraenoate (15-HETE). The 15-hydroperoxides are preferentially formed in NEUTROPHILS and LYMPHOCYTES.Phospholipases: A class of enzymes that catalyze the hydrolysis of phosphoglycerides or glycerophosphatidates. EC 3.1.-.Platelet Aggregation: The attachment of PLATELETS to one another. This clumping together can be induced by a number of agents (e.g., THROMBIN; COLLAGEN) and is part of the mechanism leading to the formation of a THROMBUS.Group VI Phospholipases A2: A calcium-independent phospholipase A2 group that may play a role in membrane phospholipid remodeling and homeostasis by controling the levels of PHOSPHATIDYLCHOLINE in mammalian cell membranes.Prostaglandins F: (9 alpha,11 alpha,13E,15S)-9,11,15-Trihydroxyprost-13-en-1-oic acid (PGF(1 alpha)); (5Z,9 alpha,11,alpha,13E,15S)-9,11,15-trihydroxyprosta-5,13-dien-1-oic acid (PGF(2 alpha)); (5Z,9 alpha,11 alpha,13E,15S,17Z)-9,11,15-trihydroxyprosta-5,13,17-trien-1-oic acid (PGF(3 alpha)). A family of prostaglandins that includes three of the six naturally occurring prostaglandins. All naturally occurring PGF have an alpha configuration at the 9-carbon position. They stimulate uterine and bronchial smooth muscle and are often used as oxytocics.Calcium: 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.Fatty Acids, Omega-6: FATTY ACIDS which have the first unsaturated bond in the sixth position from the omega carbon. A typical American diet tends to contain substantially more omega-6 than OMEGA-3 FATTY ACIDS.Cells, Cultured: 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.Phospholipases A2, Cytosolic: A subcategory of phospholipases A2 that occur in the CYTOSOL.Prostaglandins H: A group of physiologically active prostaglandin endoperoxides. They are precursors in the biosynthesis of prostaglandins and thromboxanes. The most frequently encountered member of this group is the prostaglandin H2.Thromboxanes: Physiologically active compounds found in many organs of the body. They are formed in vivo from the prostaglandin endoperoxides and cause platelet aggregation, contraction of arteries, and other biological effects. Thromboxanes are important mediators of the actions of polyunsaturated fatty acids transformed by cyclooxygenase.Prostaglandin Endoperoxides: Precursors in the biosynthesis of prostaglandins and thromboxanes from arachidonic acid. They are physiologically active compounds, having effect on vascular and airway smooth muscles, platelet aggregation, etc.Prostaglandin H2: A cyclic endoperoxide intermediate produced by the action of CYCLOOXYGENASE on ARACHIDONIC ACID. It is further converted by a series of specific enzymes to the series 2 prostaglandins.Prostaglandins G: A group of physiologically active prostaglandin endoperoxides. They are precursors in the biosynthesis of prostaglandins and thromboxanes. Most frequently encountered member of this group is the prostaglandin G2.Chromatography, High Pressure Liquid: Liquid chromatographic techniques which feature high inlet pressures, high sensitivity, and high speed.Isoenzymes: Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.Thromboxane A2: An unstable intermediate between the prostaglandin endoperoxides and thromboxane B2. The compound has a bicyclic oxaneoxetane structure. It is a potent inducer of platelet aggregation and causes vasoconstriction. It is the principal component of rabbit aorta contracting substance (RCS).Alkane 1-Monooxygenase: A P450 oxidoreductase that catalyzes the hydroxylation of the terminal carbon of linear hydrocarbons such as octane and FATTY ACIDS in the omega position. The enzyme may also play a role in the oxidation of a variety of structurally unrelated compounds such as XENOBIOTICS, and STEROIDS.ZymosanEnzyme Activation: 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.Pyrones: Keto-pyrans.Leukotriene A4: (2S-(2 alpha,3 beta(1E,3E,5Z,8Z)))-3-(1,3,5,8-Tetradecatetraenyl)oxiranebutanoic acid. An unstable allylic epoxide, formed from the immediate precursor 5-HPETE via the stereospecific removal of a proton at C-10 and dehydration. Its biological actions are determined primarily by its metabolites, i.e., LEUKOTRIENE B4 and cysteinyl-leukotrienes. Alternatively, leukotriene A4 is converted into LEUKOTRIENE C4 by glutathione-S-transferase or into 5,6-di-HETE by the epoxide-hydrolase. (From Dictionary of Prostaglandins and Related Compounds, 1990)Cytosol: Intracellular fluid from the cytoplasm after removal of ORGANELLES and other insoluble cytoplasmic components.Phospholipase A2 Inhibitors: Compounds that inhibit or block the activity of a PHOSPHOLIPASE A2 enzyme.Neutrophils: Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes.Thromboxane-A Synthase: An enzyme found predominantly in platelet microsomes. It catalyzes the conversion of PGG(2) and PGH(2) (prostaglandin endoperoxides) to thromboxane A2. EC 5.3.99.5.Kinetics: The rate dynamics in chemical or physical systems.Platelet Activating Factor: A phospholipid derivative formed by PLATELETS; BASOPHILS; NEUTROPHILS; MONOCYTES; and MACROPHAGES. It is a potent platelet aggregating agent and inducer of systemic anaphylactic symptoms, including HYPOTENSION; THROMBOCYTOPENIA; NEUTROPENIA; and BRONCHOCONSTRICTION.Fatty Acids, Essential: Long chain organic acid molecules that must be obtained from the diet. Examples are LINOLEIC ACIDS and LINOLENIC ACIDS.Aspirin: The prototypical analgesic used in the treatment of mild to moderate pain. It has anti-inflammatory and antipyretic properties and acts as an inhibitor of cyclooxygenase which results in the inhibition of the biosynthesis of prostaglandins. Aspirin also inhibits platelet aggregation and is used in the prevention of arterial and venous thrombosis. (From Martindale, The Extra Pharmacopoeia, 30th ed, p5)Rabbits: The species Oryctolagus cuniculus, in the family Leporidae, order LAGOMORPHA. Rabbits are born in burrows, furless, and with eyes and ears closed. In contrast with HARES, rabbits have 22 chromosome pairs.Dinoprost: A naturally occurring prostaglandin that has oxytocic, luteolytic, and abortifacient activities. Due to its vasocontractile properties, the compound has a variety of other biological actions.Fatty Acids, Omega-3: A group of fatty acids, often of marine origin, which have the first unsaturated bond in the third position from the omega carbon. These fatty acids are believed to reduce serum triglycerides, prevent insulin resistance, improve lipid profile, prolong bleeding times, reduce platelet counts, and decrease platelet adhesiveness.Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.DiglyceridesMicrosomes: Artifactual vesicles formed from the endoplasmic reticulum when cells are disrupted. They are isolated by differential centrifugation and are composed of three structural features: rough vesicles, smooth vesicles, and ribosomes. Numerous enzyme activities are associated with the microsomal fraction. (Glick, Glossary of Biochemistry and Molecular Biology, 1990; from Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed)Protein Kinase C: 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.Prostaglandins D: Physiologically active prostaglandins found in many tissues and organs. They show pressor activity, are mediators of inflammation, and have potential antithrombotic effects.Group II Phospholipases A2: A subcategory of secreted phospholipases A2 that includes enzymes isolated from a variety of sources. The creation of this group is based upon similarities in the structural determinants of the enzymes including a negatively charged carboxy-terminal segment.Gas Chromatography-Mass Spectrometry: A microanalytical technique combining mass spectrometry and gas chromatography for the qualitative as well as quantitative determinations of compounds.Phosphatidylinositols: Derivatives of phosphatidic acids in which the phosphoric acid is bound in ester linkage to the hexahydroxy alcohol, myo-inositol. Complete hydrolysis yields 1 mole of glycerol, phosphoric acid, myo-inositol, and 2 moles of fatty acids.Lipid Peroxides: Peroxides produced in the presence of a free radical by the oxidation of unsaturated fatty acids in the cell in the presence of molecular oxygen. The formation of lipid peroxides results in the destruction of the original lipid leading to the loss of integrity of the membranes. They therefore cause a variety of toxic effects in vivo and their formation is considered a pathological process in biological systems. Their formation can be inhibited by antioxidants, such as vitamin E, structural separation or low oxygen tension.Tetradecanoylphorbol Acetate: A phorbol ester found in CROTON OIL with very effective tumor promoting activity. It stimulates the synthesis of both DNA and RNA.Bradykinin: A nonapeptide messenger that is enzymatically produced from KALLIDIN in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from MAST CELLS during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter.gamma-Linolenic Acid: An omega-6 fatty acid produced in the body as the delta 6-desaturase metabolite of linoleic acid. It is converted to dihomo-gamma-linolenic acid, a biosynthetic precursor of monoenoic prostaglandins such as PGE1. (From Merck Index, 11th ed)Fatty Acid Desaturases: A family of enzymes that catalyze the stereoselective, regioselective, or chemoselective syn-dehydrogenation reactions. They function by a mechanism that is linked directly to reduction of molecular OXYGEN.Lysophosphatidylcholines: Derivatives of PHOSPHATIDYLCHOLINES obtained by their partial hydrolysis which removes one of the fatty acid moieties.Phosphatidylcholines: Derivatives of phosphatidic acids in which the phosphoric acid is bound in ester linkage to a choline moiety. Complete hydrolysis yields 1 mole of glycerol, phosphoric acid and choline and 2 moles of fatty acids.Epoxide Hydrolases: Enzymes that catalyze reversibly the formation of an epoxide or arene oxide from a glycol or aromatic diol, respectively.5-Lipoxygenase-Activating Proteins: Scaffolding proteins that play an important role in the localization and activation of 5-LIPOXYGENASE.Phosphatidic Acids: 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.Cyclohexanones: Cyclohexane ring substituted by one or more ketones in any position.Melitten: Basic polypeptide from the venom of the honey bee (Apis mellifera). It contains 26 amino acids, has cytolytic properties, causes contracture of muscle, releases histamine, and disrupts surface tension, probably due to lysis of cell and mitochondrial membranes.Glycerides: GLYCEROL esterified with FATTY ACIDS.Linolenic Acids: Eighteen-carbon essential fatty acids that contain three double bonds.Lipoxins: Trihydroxy derivatives of eicosanoic acids. They are primarily derived from arachidonic acid, however eicosapentaenoic acid derivatives also exist. Many of them are naturally occurring mediators of immune regulation.Cell Line: Established cell cultures that have the potential to propagate indefinitely.alpha-Linolenic Acid: A fatty acid that is found in plants and involved in the formation of prostaglandins.Type C Phospholipases: 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.Ionophores: Chemical agents that increase the permeability of biological or artificial lipid membranes to specific ions. Most ionophores are relatively small organic molecules that act as mobile carriers within membranes or coalesce to form ion permeable channels across membranes. Many are antibiotics, and many act as uncoupling agents by short-circuiting the proton gradient across mitochondrial membranes.Linoleoyl-CoA Desaturase: An enzyme that catalyzes the syn-dehydrogenation of linoleol-CoA gamma-linolenoyl-CoA. It was formerly characterized as EC 1.14.99.25.Oxygenases: Oxidases that specifically introduce DIOXYGEN-derived oxygen atoms into a variety of organic molecules.Intramolecular Oxidoreductases: Enzymes of the isomerase class that catalyze the oxidation of one part of a molecule with a corresponding reduction of another part of the same molecule. They include enzymes converting aldoses to ketoses (ALDOSE-KETOSE ISOMERASES), enzymes shifting a carbon-carbon double bond (CARBON-CARBON DOUBLE BOND ISOMERASES), and enzymes transposing S-S bonds (SULFUR-SULFUR BOND ISOMERASES). (From Enzyme Nomenclature, 1992) EC 5.3.Prostaglandin Endoperoxides, Synthetic: Synthetic compounds that are analogs of the naturally occurring prostaglandin endoperoxides and that mimic their pharmacologic and physiologic activities. They are usually more stable than the naturally occurring compounds.Cyclooxygenase 2 Inhibitors: A subclass of cyclooxygenase inhibitors with specificity for CYCLOOXYGENASE-2.Rats, Sprague-Dawley: A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.Rats, Inbred Strains: Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding.Receptors, Thromboxane: Cell surface proteins that bind THROMBOXANES with high affinity and trigger intracellular changes influencing the behavior of cells. Some thromboxane receptors act via the inositol phosphate and diacylglycerol second messenger systems.Naphthalenes: Two-ring crystalline hydrocarbons isolated from coal tar. They are used as intermediates in chemical synthesis, as insect repellents, fungicides, lubricants, preservatives, and, formerly, as topical antiseptics.Signal Transduction: 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.Thrombin: An enzyme formed from PROTHROMBIN that converts FIBRINOGEN to FIBRIN.Endocannabinoids: Fatty acid derivatives that have specificity for CANNABINOID RECEPTORS. They are structurally distinct from CANNABINOIDS and were originally discovered as a group of endogenous CANNABINOID RECEPTOR AGONISTS.15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid: A stable prostaglandin endoperoxide analog which serves as a thromboxane mimetic. Its actions include mimicking the hydro-osmotic effect of VASOPRESSIN and activation of TYPE C PHOSPHOLIPASES. (From J Pharmacol Exp Ther 1983;224(1): 108-117; Biochem J 1984;222(1):103-110)Fish Oils: Oils high in unsaturated fats extracted from the bodies of fish or fish parts, especially the LIVER. Those from the liver are usually high in VITAMIN A. The oils are used as DIETARY SUPPLEMENTS. They are also used in soaps and detergents and as protective coatings.Dietary Fats, Unsaturated: Unsaturated fats or oils used in foods or as a food.N-Formylmethionine Leucyl-Phenylalanine: A formylated tripeptide originally isolated from bacterial filtrates that is positively chemotactic to polymorphonuclear leucocytes, and causes them to release lysosomal enzymes and become metabolically activated.Lipoxygenases: Dioxygenases that catalyze the peroxidation of methylene-interrupted UNSATURATED FATTY ACIDS.Phosphatidylethanolamines: Derivatives of phosphatidic acids in which the phosphoric acid is bound in ester linkage to an ethanolamine moiety. Complete hydrolysis yields 1 mole of glycerol, phosphoric acid and ethanolamine and 2 moles of fatty acids.Seminal Vesicles: A saclike, glandular diverticulum on each ductus deferens in male vertebrates. It is united with the excretory duct and serves for temporary storage of semen. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)Prostaglandin D2: The principal cyclooxygenase metabolite of arachidonic acid. It is released upon activation of mast cells and is also synthesized by alveolar macrophages. Among its many biological actions, the most important are its bronchoconstrictor, platelet-activating-factor-inhibitory, and cytotoxic effects.Anthralin: An anthracene derivative that disrupts MITOCHONDRIA function and structure and is used for the treatment of DERMATOSES, especially PSORIASIS. It may cause FOLLICULITIS.Oleic Acid: An unsaturated fatty acid that is the most widely distributed and abundant fatty acid in nature. It is used commercially in the preparation of oleates and lotions, and as a pharmaceutical solvent. (Stedman, 26th ed)Ibuprofen: A nonsteroidal anti-inflammatory agent with analgesic properties used in the therapy of rheumatism and arthritis.Prostaglandin Antagonists: Compounds that inhibit the action of prostaglandins.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Isoprostanes: A series of prostaglandin-like compounds that are produced by the attack of free-radical species on unsaturated fatty acids, especially ARACHIDONIC ACID, of cellular MEMBRANES. Once cleaved from the lipid membrane by the action of phospholipases they can circulate into various bodily fluids and eventually be excreted. Although these compounds resemble enzymatically synthesized prostaglandins their stereoisometric arrangement is usually different than the "naturally occurring" compounds.Chromatography, Gas: Fractionation of a vaporized sample as a consequence of partition between a mobile gaseous phase and a stationary phase held in a column. Two types are gas-solid chromatography, where the fixed phase is a solid, and gas-liquid, in which the stationary phase is a nonvolatile liquid supported on an inert solid matrix.NitrobenzenesInositol Phosphates: Phosphoric acid esters of inositol. They include mono- and polyphosphoric acid esters, with the exception of inositol hexaphosphate which is PHYTIC ACID.Macrophages: The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.)TritiumMembrane Lipids: Lipids, predominantly phospholipids, cholesterol and small amounts of glycolipids found in membranes including cellular and intracellular membranes. These lipids may be arranged in bilayers in the membranes with integral proteins between the layers and peripheral proteins attached to the outside. Membrane lipids are required for active transport, several enzymatic activities and membrane formation.Carbon Radioisotopes: Unstable isotopes of carbon that decay or disintegrate emitting radiation. C atoms with atomic weights 10, 11, and 14-16 are radioactive carbon isotopes.Polyunsaturated Alkamides: Amides composed of unsaturated aliphatic FATTY ACIDS linked with AMINES by an amide bond. They are most prominent in ASTERACEAE; PIPERACEAE; and RUTACEAE; and also found in ARISTOLOCHIACEAE; BRASSICACEAE; CONVOLVULACEAE; EUPHORBIACEAE; MENISPERMACEAE; POACEAE; and SOLANACEAE. They are recognized by their pungent taste and for causing numbing and salivation.Peroxides: A group of compounds that contain a bivalent O-O group, i.e., the oxygen atoms are univalent. They can either be inorganic or organic in nature. Such compounds release atomic (nascent) oxygen readily. Thus they are strong oxidizing agents and fire hazards when in contact with combustible materials, especially under high-temperature conditions. The chief industrial uses of peroxides are as oxidizing agents, bleaching agents, and initiators of polymerization. (From Hawley's Condensed Chemical Dictionary, 11th ed)Erucic Acids: cis-13-Docosenoic Acids. 22-Carbon monounsaturated, monocarboxylic acids.Mortierella: A genus of zygomycetous fungi of the family Mortierellaceae, order MUCORALES. Its species are abundant in soil and can cause rare infections in humans and animals. Mortierella alpinais is used for production of arachidonic acid.Plasmalogens: GLYCEROPHOSPHOLIPIDS in which one of the two acyl chains is attached to glycerol with an ether alkenyl linkage instead of an ester as with the other glycerophospholipids.Pyrazoles: Azoles of two nitrogens at the 1,2 positions, next to each other, in contrast with IMIDAZOLES in which they are at the 1,3 positions.Chromatography, Thin Layer: 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)Leukotriene C4: The conjugation product of LEUKOTRIENE A4 and glutathione. It is the major arachidonic acid metabolite in macrophages and human mast cells as well as in antigen-sensitized lung tissue. It stimulates mucus secretion in the lung, and produces contractions of nonvascular and some VASCULAR SMOOTH MUSCLE. (From Dictionary of Prostaglandins and Related Compounds, 1990)Lipid Metabolism: Physiological processes in biosynthesis (anabolism) and degradation (catabolism) of LIPIDS.Terpenes: A class of compounds composed of repeating 5-carbon units of HEMITERPENES.Endothelium, Vascular: Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components.Platelet Activation: A series of progressive, overlapping events, triggered by exposure of the PLATELETS to subendothelial tissue. These events include shape change, adhesiveness, aggregation, and release reactions. When carried through to completion, these events lead to the formation of a stable hemostatic plug.Rats, Wistar: A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.1-Acylglycerophosphocholine O-Acyltransferase: An enzyme localized predominantly within the plasma membrane of lymphocytes. It catalyzes the transfer of long-chain fatty acids, preferentially unsaturated fatty acids, to lysophosphatides with the formation of 1,2-diacylglycero-3-phosphocholine and CoA. EC 2.3.1.23.Stearic Acids: A group of compounds that are derivatives of octadecanoic acid which is one of the most abundant fatty acids found in animal lipids. (Stedman, 25th ed)Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.Proadifen: An inhibitor of drug metabolism and CYTOCHROME P-450 ENZYME SYSTEM activity.Mass Spectrometry: An analytical method used in determining the identity of a chemical based on its mass using mass analyzers/mass spectrometers.Guinea Pigs: A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research.Virulence Factors, Bordetella: A set of BACTERIAL ADHESINS and TOXINS, BIOLOGICAL produced by BORDETELLA organisms that determine the pathogenesis of BORDETELLA INFECTIONS, such as WHOOPING COUGH. They include filamentous hemagglutinin; FIMBRIAE PROTEINS; pertactin; PERTUSSIS TOXIN; ADENYLATE CYCLASE TOXIN; dermonecrotic toxin; tracheal cytotoxin; Bordetella LIPOPOLYSACCHARIDES; and tracheal colonization factor.AcetophenonesF2-Isoprostanes: Isoprostanes derived from the free radical oxidation of ARACHIDONIC ACID. Although similar in structure to enzymatically synthesized prostaglandin F2alpha (DINOPROST), they occur through non-enzymatic oxidation of cell membrane lipids.Catechols: A group of 1,2-benzenediols that contain the general formula R-C6H5O2.Cyclic AMP: An adenine nucleotide containing one phosphate group which is esterified to both the 3'- and 5'-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and ACTH.Substrate Specificity: A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.Muscle, Smooth, Vascular: The nonstriated involuntary muscle tissue of blood vessels.Stereoisomerism: The phenomenon whereby compounds whose molecules have the same number and kind of atoms and the same atomic arrangement, but differ in their spatial relationships. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 5th ed)Cattle: Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor.Pertussis Toxin: 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.Second Messenger Systems: 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.Alkaloids: Organic nitrogenous bases. Many alkaloids of medical importance occur in the animal and vegetable kingdoms, and some have been synthesized. (Grant & Hackh's Chemical Dictionary, 5th ed)Sulfonamides: A group of compounds that contain the structure SO2NH2.Anti-Inflammatory Agents, Non-Steroidal: Anti-inflammatory agents that are non-steroidal in nature. In addition to anti-inflammatory actions, they have analgesic, antipyretic, and platelet-inhibitory actions.They act by blocking the synthesis of prostaglandins by inhibiting cyclooxygenase, which converts arachidonic acid to cyclic endoperoxides, precursors of prostaglandins. Inhibition of prostaglandin synthesis accounts for their analgesic, antipyretic, and platelet-inhibitory actions; other mechanisms may contribute to their anti-inflammatory effects.Superoxides: Highly reactive compounds produced when oxygen is reduced by a single electron. In biological systems, they may be generated during the normal catalytic function of a number of enzymes and during the oxidation of hemoglobin to METHEMOGLOBIN. In living organisms, SUPEROXIDE DISMUTASE protects the cell from the deleterious effects of superoxides.Egtazic Acid: A chelating agent relatively more specific for calcium and less toxic than EDETIC ACID.Group V Phospholipases A2: A subcategory of secreted phospholipases A2 that contains both a negatively charged carboxy-terminal segment and interfacial-binding region specific for PHOSPHATIDYL CHOLINE-containing membranes. This enzyme group may play a role in the release of ARACHIDONIC ACID from phospholipid membranes.Kidney: Body organ that filters blood for the secretion of URINE and that regulates ion concentrations.RNA, Messenger: RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.Lipid Peroxidation: Peroxidase catalyzed oxidation of lipids using hydrogen peroxide as an electron acceptor.Cell Membrane: The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.Endothelium: A layer of epithelium that lines the heart, blood vessels (ENDOTHELIUM, VASCULAR), lymph vessels (ENDOTHELIUM, LYMPHATIC), and the serous cavities of the body.Lipids: A generic term for fats and lipoids, the alcohol-ether-soluble constituents of protoplasm, which are insoluble in water. They comprise the fats, fatty oils, essential oils, waxes, phospholipids, glycolipids, sulfolipids, aminolipids, chromolipids (lipochromes), and fatty acids. (Grant & Hackh's Chemical Dictionary, 5th ed)Mixed Function Oxygenases: Widely distributed enzymes that carry out oxidation-reduction reactions in which one atom of the oxygen molecule is incorporated into the organic substrate; the other oxygen atom is reduced and combined with hydrogen ions to form water. They are also known as monooxygenases or hydroxylases. These reactions require two substrates as reductants for each of the two oxygen atoms. There are different classes of monooxygenases depending on the type of hydrogen-providing cosubstrate (COENZYMES) required in the mixed-function oxidation.Oxidation-Reduction: A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471).Aristolochic Acids: Nitro-phenanthrenes occurring in ARISTOLOCHIACEAE and other plants. They derive from stephanine (APORPHINES) by oxidative ring cleavage. The nitro group is a reactive alkylator (ALKYLATING AGENTS) that binds to biological macromolecules. Ingestion by humans is associated with nephropathy (NEPHRITIS). There is no relationship to the similar named aristolochene (SESQUITERPENES).Receptors, Prostaglandin: Cell surface receptors that bind prostaglandins with high affinity and trigger intracellular changes which influence the behavior of cells. Prostaglandin receptor subtypes have been tentatively named according to their relative affinities for the endogenous prostaglandins. They include those which prefer prostaglandin D2 (DP receptors), prostaglandin E2 (EP1, EP2, and EP3 receptors), prostaglandin F2-alpha (FP receptors), and prostacyclin (IP receptors).Enzyme Induction: An increase in the rate of synthesis of an enzyme due to the presence of an inducer which acts to derepress the gene responsible for enzyme synthesis.Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.Prostaglandins, Synthetic: Compounds obtained by chemical synthesis that are analogs or derivatives of naturally occurring prostaglandins and that have similar activity.Liver: A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.Biological Factors: Endogenously-synthesized compounds that influence biological processes not otherwise classified under ENZYMES; HORMONES or HORMONE ANTAGONISTS.Group X Phospholipases A2: A secreted phospholipase A2 subtype that contains a interfacial-binding region with specificity for PHOSPHATIDYLCHOLINE. This enzyme group may play a role in eliciting ARACHIDONIC ACID release from intact cellular membranes and from LOW DENSITY LIPOPROTEINS. Members of this group bind specifically to PHOSPHOLIPASE A2 RECEPTORS.Fatty Acids, Nonesterified: FATTY ACIDS found in the plasma that are complexed with SERUM ALBUMIN for transport. These fatty acids are not in glycerol ester form.Potassium Channels, Tandem Pore Domain: Potassium channels that contain two pores in tandem. They are responsible for baseline or leak currents and may be the most numerous of all K channels.Meclofenamic Acid: A non-steroidal anti-inflammatory agent with antipyretic and antigranulation activities. It also inhibits prostaglandin biosynthesis.Stimulation, Chemical: The increase in a measurable parameter of a PHYSIOLOGICAL PROCESS, including cellular, microbial, and plant; immunological, cardiovascular, respiratory, reproductive, urinary, digestive, neural, musculoskeletal, ocular, and skin physiological processes; or METABOLIC PROCESS, including enzymatic and other pharmacological processes, by a drug or other chemical.Receptors, Eicosanoid: Cell surface proteins that bind eicosanoids with high affinity and trigger intracellular changes influencing the behavior of cells. Among the eicosanoid receptors are receptors for the prostaglandins, thromboxanes, and leukotrienes.Phospholipases A2, Secretory: A subcategory of phospholipases A2 that are secreted from cells. They are 14 kDa proteins containing multiple disulfide-bonds and access their substrate via an interfacial binding site that interacts with phospholipid membranes. In addition specific PHOSPHOLIPASE A2 RECEPTORS can bind to and internalize the enzymes.Phospholipase D: 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.Autacoids: A chemically diverse group of substances produced by various tissues in the body that cause slow contraction of smooth muscle; they have other intense but varied pharmacologic activities.Flurbiprofen: An anti-inflammatory analgesic and antipyretic of the phenylalkynoic acid series. It has been shown to reduce bone resorption in periodontal disease by inhibiting CARBONIC ANHYDRASE.Tin Compounds: Inorganic compounds that contain tin as an integral part of the molecule.Plant Oils: Oils derived from plants or plant products.Isomerism: The phenomenon whereby certain chemical compounds have structures that are different although the compounds possess the same elemental composition. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 5th ed)

Mechanisms of prostaglandin E2 release by intact cells expressing cyclooxygenase-2: evidence for a 'two-component' model. (1/4381)

Prostaglandin (PG) release in cells expressing constitutive cyclooxygenase-1 is known to be regulated by liberation of arachidonic acid by phospholipase A2 followed by metabolism by cyclooxygenase. However, the relative contribution of phospholipase A2 to the release of PGs in cells expressing cyclooxygenase-2 is not clear. We addressed this question by using radioimmunoassay to measure PGE2 release by human cells (A549) induced to express cyclooxygenase-2 (measured by Western blot analysis) by interleukin-1beta. Cells were either unstimulated or stimulated with agents known to activate phospholipase A2 (bradykinin, Des-Arg10-kallidin, or the calcium ionophore A23187) or treated with exogenous arachidonic acid. When cells were treated to express cyclooxygenase-2, the levels of PGE2 released over 15 min were undetectable; however, in the same cells stimulated with bradykinin, A23187, or arachidonic acid, large amounts of prostanoid were produced. Using selective inhibitors/antagonists, we found that the effects of bradykinin were mediated by B2 receptor activation and that prostanoid release was due to cyclooxygenase-2, and not cyclooxygenase-1, activity. In addition, we show that the release of PGE2 stimulated by either bradykinin, A23187, or arachidonic acid was inhibited by the phospholipase A2 inhibitor arachidonate trifluoromethyl ketone. Hence, we have demonstrated that PGE2 is released by two components: induction of cyclooxygenase-2 and supply of substrate, probably via activation of phospholipase A2. This is illustrated in A549 cells by a clear synergy between the cytokine interleukin-1beta and the kinin bradykinin.  (+info)

Pharmacology of LY315920/S-5920, [[3-(aminooxoacetyl)-2-ethyl-1- (phenylmethyl)-1H-indol-4-yl]oxy] acetate, a potent and selective secretory phospholipase A2 inhibitor: A new class of anti-inflammatory drugs, SPI. (2/4381)

LY315920 is a potent, selective inhibitor of recombinant human, group IIA, nonpancreatic secretory PLA2 (sPLA2). In a chromogenic isolated enzyme assay, LY315920 inhibited sPLA2 activity with an IC50 of 9 +/- 1 nM or 7.3 x 10(-6) mole fraction, which approached the stiochiometric limit of this assay. The true potency of LY315920 was defined using a deoxycholate/phosphatidylcholine assay with a mole fraction of 1.5 x 10(-6). LY315920 was 40-fold less active against human, group IB, pancreatic sPLA2 and was inactive against cytosolic PLA2 and the constitutive and inducible forms of cyclooxygenase. Human sPLA2-induced release of thromboxane A2 (TXA2) from isolated guinea pig lung bronchoalveolar lavage cells was inhibited by LY315920 with an IC50 of 0.79 microM. The release of TXA2 from these cells by N-formyl-methionyl-leucyl-phenylalanine or arachidonic acid was not inhibited. The i.v. administration of LY315920, 5 min before harvesting the bronchoalveolar lavage cells, resulted in the inhibition of sPLA2-induced production of TXA2 with an ED50 of 16.1 mg/kg. Challenge of guinea pig lung pleural strips with sPLA2 produced contractile responses that were suppressed in a concentration-dependent manner by LY315920 with an apparent KB of 83 +/- 14 nM. Contractile responses induced by arachidonic acid were not altered. Intravenous or oral administration of LY315920 to transgenic mice expressing the human sPLA2 protein inhibited serum sPLA2 activity in a dose-related manner over a 4-h time course. LY315920 is a potent and selective sPLA2 inhibitor and represents a new class of anti-inflammatory agent designated SPI. This agent is currently undergoing clinical evaluation and should help to define the role of sPLA2 in various inflammatory disease states.  (+info)

Calcium responses induced by acetylcholine in submucosal arterioles of the guinea-pig small intestine. (3/4381)

1. Calcium responses induced by brief stimulation with acetylcholine (ACh) were assessed from the fluorescence changes in fura-2 loaded submucosal arterioles of the guinea-pig small intestine. 2. Initially, 1-1.5 h after loading with fura-2 (fresh tissues), ACh increased [Ca2+]i in a concentration-dependent manner. This response diminished with time, and finally disappeared in 2-3 h (old tissues). 3. Ba2+ elevated [Ca2+]i to a similar extent in both fresh and old tissues. ACh further increased the Ba2+-elevated [Ca2+]i in fresh tissues, but reduced it in old tissues. Responses were not affected by either indomethacin or nitroarginine. 4. In fresh mesenteric arteries, mechanical removal of endothelial cells abolished the ACh-induced increase in [Ca2+]i, with no alteration of [Ca2+]i at rest and during elevation with Ba2+. 5. In the presence of indomethacin and nitroarginine, high-K+ solution elevated [Ca2+]i in both fresh and old tissues. Subsequent addition of ACh further increased [Ca2+]i in fresh tissues without changing it in old tissues. 6. Proadifen, an inhibitor of the enzyme cytochrome P450 mono-oxygenase, inhibited the ACh-induced changes in [Ca2+]i in both fresh and Ba2+-stimulated old tissues. It also inhibited the ACh-induced hyperpolarization. 7. In fresh tissues, the ACh-induced Ca2+ response was not changed by apamin, charybdotoxin (CTX), 4-aminopyridine (4-AP) or glibenclamide. In old tissues in which [Ca2+]i had previously been elevated with Ba2+, the ACh-induced Ca2+ response was inhibited by CTX but not by apamin, 4-AP or glibenclamide. 8. It is concluded that in submucosal arterioles, ACh elevates endothelial [Ca2+]i and reduces muscular [Ca2+]i, probably through the hyperpolarization of endothelial or smooth muscle membrane by activating CTX-sensitive K+ channels.  (+info)

The cyclo-oxygenase-dependent regulation of rabbit vein contraction: evidence for a prostaglandin E2-mediated relaxation. (4/4381)

1. Arachidonic acid (0.01-1 microM) induced relaxation of precontracted rings of rabbit saphenous vein, which was counteracted by contraction at concentrations higher than 1 microM. Concentrations higher than 1 microM were required to induce dose-dependent contraction of vena cava and thoracic aorta from the same animals. 2. Pretreatment with a TP receptor antagonist (GR32191B or SQ29548, 3 microM) potentiated the relaxant effect in the saphenous vein, revealed a vasorelaxant component in the vena cava response and did not affect the response of the aorta. 3. Removal of the endothelium from the venous rings, caused a 10 fold rightward shift in the concentration-relaxation curves to arachidonic acid. Whether or not the endothelium was present, the arachidonic acid-induced relaxations were prevented by indomethacin (10 microM) pretreatment. 4. In the saphenous vein, PGE2 was respectively a 50 and 100 fold more potent relaxant prostaglandin than PGI2 and PGD2. Pretreatment with the EP4 receptor antagonist, AH23848B, shifted the concentration-relaxation curves of this tissue to arachidonic acid in a dose-dependent manner. 5. In the presence of 1 microM arachidonic acid, venous rings produced 8-10 fold more PGE2 than did aorta whereas 6keto-PGF1alpha and TXB2 productions remained comparable. 6. Intact rings of saphenous vein relaxed in response to A23187. Pretreatment with L-NAME (100 microM) or indomethacin (10 microM) reduced this response by 50% whereas concomitant pretreatment totally suppressed it. After endothelium removal, the remaining relaxing response to A23187 was prevented by indomethacin but not affected by L-NAME. 7. We conclude that stimulation of the cyclo-oxygenase pathway by arachidonic acid induced endothelium-dependent, PGE2/EP4 mediated relaxation of the rabbit saphenous vein. This process might participate in the A23187-induced relaxation of the saphenous vein and account for a relaxing component in the response of the vena cava to arachidonic acid. It was not observed in thoracic aorta because of the lack of a vasodilatory receptor and/or the poorer ability of this tissue than veins to produce PGE2.  (+info)

Plasmalogen status influences docosahexaenoic acid levels in a macrophage cell line. Insights using ether lipid-deficient variants. (5/4381)

Previously, this laboratory reported the isolation of variants, RAW. 12 and RAW.108, from the macrophage-like cell line RAW 264.7 that are defective in plasmalogen biosynthesis [Zoeller, R.A. et al. 1992. J. Biol. Chem. 267: 8299-8306]. Fatty acid analysis showed significant changes in the mutants in the ethanolamine phospholipids (PE), the only phospholipid class in which the plasmalogen species, plasmenylethanolamine, contributes significantly. Within the PE fraction, docosapentaenoic (DPA; 22:5n-3) and docosahexaenoic (DHA; 22:6n-3) acids were reduced by approximately 50% in the variants while the levels of arachidonic acid (AA; 20:4n-6) remained unaffected. The decrease in DHA was accompanied by a 50% decrease in labeling PE with [3H]DHA over a 90-min period. Restoration of plasmenylethanolamine by supplementing the growth medium with sn -1-hexadecylglycerol (HG) completely reversed these changes in RAW. 108. Pre-existing pools of plasmenylethanolamine were not required for restoration of normal [3H]DHA labeling; addition of HG only during the labeling period was sufficient. Due to the loss of Delta1'-desaturase in RAW.12, HG supplementation resulted in the accumulation of plasmenylethanolamine's immediate biosynthetic precursor, plasmanylethanolamine. Even though this latter phospholipid contained only the ether functionality (lacking the vinyl ether double bond) it was sufficient to restore wild type-like fatty acid composition and DHA labeling of the ethanolamine phospholipids, identifying the ether bond as a structural determinant for this specificity. In summary, we have used these mutants to establish that the plasmalogen status of a cell can influence the levels of certain polyunsaturated fatty acids. These results support the notion that certain polyunsaturated fatty acids, such as DHA, can be selectively targeted to plasmalogens and that this targeting occurs during de novo biosynthesis, or shortly thereafter, through modification of nascent plasmalogen pools.  (+info)

Arachidonic acid in platelet microparticles up-regulates cyclooxygenase-2-dependent prostaglandin formation via a protein kinase C/mitogen-activated protein kinase-dependent pathway. (6/4381)

Activation of platelets results in shedding of membrane microparticles (MP) with potentially bioactive properties. Platelet MP modulate platelet, monocyte, and vascular endothelial cell function, both by direct effects of MP arachidonic acid (AA) and by its metabolism to bioactive prostanoids. We have previously reported that platelet MP induce expression of cyclooxygenase (COX)-2 and prostacyclin production in monocytes and endothelial cells. To elucidate further the molecular mechanisms that underlie MP-induced up-regulation of COX-2 expression, we investigated the response of a human monocytoid (U-937) cell line to platelet MP stimulation. In U-937 cells, MP-induced COX-2 expression and eicosanoid formation is prevented by pharmacological inhibitors of protein kinase C (PKC), PI 3-kinase, mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase, and p38 kinase. Treatment with the PI 3-kinase inhibitors wortmannin and LY294002 also blocked MP-induced p42/p44 MAPK, p38, and JNK1 phosphorylation. Conversely, platelet MP stimulation of U-937 cells results in direct activation of PKC, p42/p44 MAPK, p38 kinase, and c-Jun N-terminal kinase (JNK) as well as activation of the transcription factors c-Jun and Elk-1. However, MP failed to activate the cAMP response element. Activation of U-937 cells by MP induces translocation of classical (PKCbeta), novel (PKCdelta) and atypical (PKCzeta and PKClambda) isozymes of PKC from the cytosol to the membrane, with concomitant activation of downstream MAPK. While MP-induced activation of p42/p44 MAPK and p38 kinase is transient, a sustained activation of JNK1 was observed. Although PKC activation is required for MP-induced p42/p44 MAPK, activation of the stress kinases p38 and JNK1 was PKC-independent. The fatty acid fraction of the MP accounted for these effects, which were mimicked by MP AA. Rather than acting directly via nuclear receptors, MP AA activates COX-2-dependent prostaglandin production by a PKC/p42/p44 MAPK/p38 kinase-sensitive pathway in which PI 3-kinase plays a significant role. MP AA also stimulates transcriptional activation of COX-2 as well as c-Jun and Elk-1.  (+info)

Effect of prostanoids and their precursors on the aggregation of rainbow trout thrombocytes. (7/4381)

The role of prostanoids and their precursor fatty acids in the aggregatory response of thrombocytes (platelet equivalents of fish) from the rainbow trout, Oncorhynchus mykiss, was studied. Aggregation of these cells was induced by the thromboxane mimetic U-46619 or arachidonic acid (AA) in the presence of human or trout fibrinogen. The production of TXB2/3 by thrombocytes in response to stimulation with AA was inhibited by aspirin, ibuprofen, and indomethacin. However, thrombocyte aggregation in response to AA stimulation was not significantly altered by these agents at the concentrations tested (10-100 microM), with the exception of indomethacin at 20 and 40 microM. Effects on cytosolic calcium concentration have been suggested as an alternative mechanism for the inhibitory action of indomethacin on human platelet aggregation. The present study, however, failed to identify this as a mechanism for the inhibition of U-46619-induced trout thrombocyte aggregation by indomethacin. The polyunsaturated fatty acids docosahexaenoic acid and eicosapentaenoic acid both exhibited an inhibitory effect on U-46619-induced thrombocyte aggregation similar to that observed with mammalian platelets. Unlike the case in mammalian hemostasis, prostacyclin inhibited thrombocyte aggregation only at high concentrations (>5 microM). Prostaglandin E2, however, inhibited thrombocyte aggregation at much lower concentrations (>0.01 microM), suggesting that it may be the major inhibitory eicosanoid in trout.  (+info)

Endothelin-1 and CYP450 arachidonate metabolites interact to promote tissue injury in DOCA-salt hypertension. (8/4381)

Inhibition of cytochrome P-450 (CYP450) enzymes with cobalt chloride (CoCl2) prevented hypertension, organ hypertrophy, and renal injury induced by DOCA and salt (1% NaCl) in uninephrectomized (UNx) rats. Systolic blood pressure (SBP) rose to 193 +/- 6 mmHg by day 21 from control levels of 150 +/- 7 mmHg in response to DOCA-salt treatment, a rise that was prevented by CoCl2 (24 mg. kg-1. 24 h-1). The effects of DOCA-salt treatment, which increased protein excretion to 88.3 +/- 6.9 mg/24 h on day 21 from 9.0 +/- 1.1 mg/24 h on day 3, were prevented by CoCl2. CoCl2 also attenuated the renal and left ventricular hypertrophy and the increase in media-to-lumen ratio in hypertensive rats. DOCA-salt treatment increased excretion of endothelin (ET)-1 from 81 +/- 17 to 277 +/- 104 pg. 100 g body wt-1. 24 h-1 associated with a fourfold increase in 20-hydroxyeicosatetraenoic acid (20-HETE) excretion from 3.0 +/- 1.1 to 12.2 +/- 1.9 ng. 100 g body wt-1. 24 h-1 (days 3 vs. 21). CoCl2 blunted these increases by 58 and 72%, respectively. In aortic rings pulsed with [3H]thymidine, ET-1 increased its incorporation. Dibromododec-11-enoic acid, an inhibitor of 20-HETE synthesis, attenuated ET-1-induced increases in [3H]thymidine incorporation. We distinguished effects of CoCl2 acting via CO generation vs. suppression of CYP450-arachidonic acid metabolism by treating UNx-salt-DOCA rats with 1-aminobenzotriazole (ABT), which suppresses CYP450 enzyme activity, and compared these results to those produced by CoCl2. ABT reduced hypertension, as did CoCl2. Unlike CoCl2, ABT did not prevent organ hypertrophy and proteinuria, suggesting that these effects were partially related to CO formation. Blockade of the ETA receptor with BMS-182874 reduced SBP, organ hypertrophy, and proteinuria, indicating the importance of ET-initiated abnormalities to the progression of lesions in UNx-salt-DOCA.  (+info)

It is well recognized that the CYP-derived eicosanoids constitute a new member of the arachidonic acid cascade with important implications in the regulation of physiological and pathophysiological processes. These metabolites are formed endogenously in various tissues and exert potent biological effects on cellular functions. Studies of their role in normal and diseased cells and tissues are impeded by the difficulty in selectively targeting their synthesis or their effects, because these metabolites are generated from multiple closely related proteins of the CYP superfamily. Consequently, the development of enzyme inhibitors that target specific isoforms/reactions should aid in the study of their pathophysiological roles.. We have synthesized a series of fatty acid/arachidonic acid analogs and tested their potency and selectivity in inhibiting arachidonic acid epoxidation and ω-hydroxylation reactions in rat renal microsomes. Our study confirms that the widely used, terminal acetylenic ...
Although lithium has been used therapeutically to treat patients with bipolar disorder for over 50 years, its mechanism of action, as well as that of other drugs used to treat bipolar disorder, is not agreed upon. In the present paper, I review studies in unanaesthetized rats using a neuropharmacological approach, combined with kinetic, biochemical and molecular biology techniques, demonstrating that chronic administration of three commonly used mood stabilizers (lithium, valproic acid and carbamazepine), at therapeutically relevant doses, selectively target the brain arachidonic acid cascade. Upon chronic administration, lithium and carbamazepine decrease the binding activity of activator protein-2 and, in turn, the transcription, translation and activity of its arachidonic acid-selective calcium-dependent phospholipase A2 gene product, whereas chronic valproic acid non-competitively inhibits long-chain acyl-CoA synthetase. The net overlapping effects of the three mood stabilizers are decreased ...
Definition of Arachidonic acid cascade with photos and pictures, translations, sample usage, and additional links for more information.
Arachidonic acid supplementation in daily doses of 1,000-1,500 mg for 50 days has been well tolerated during several clinical studies, with no significant side effects reported. All common markers of health, including kidney and liver function,[35] serum lipids,[39] immunity,[40] and platelet aggregation[34] appear to be unaffected with this level and duration of use. Furthermore, higher concentrations of ARA in muscle tissue may be correlated with improved insulin sensitivity.[41] Arachidonic acid supplementation of the diets of healthy adults appears to offer no toxicity or significant safety risk. While studies looking at arachidonic acid supplementation in sedentary subjects have failed to find changes in resting inflammatory markers in doses up to 1,500 mg daily, strength-trained subjects may respond differently. One study reported a significant reduction in resting inflammation (via marker IL-6) in young men supplementing 1,000 mg/day of arachidonic acid for 50 days in combination with ...
TY - JOUR. T1 - Mechanism of thrombin-induced arachidonic acid release in osteoblast-like cells. AU - Suzuki, A.. AU - Kozawa, O.. AU - Shinoda, J.. AU - Watanabe-Tomita, Y.. AU - Saito, H.. AU - Oiso, Y.. PY - 1997/6. Y1 - 1997/6. N2 - In a previous study, we have reported that thrombin stimulates phosphatidylcholine hydrolysis by phospholipase (PL) D, but has little effect on phosphoinositide hydrolysis by PLC in osteoblast-like MC3T3-E1 cells. In the present study, we investigated the mechanism of the thrombin-induced arachidonic acid (AA) release in MC3T3-E1 cells. Thrombin stimulated AA release dose dependently in the range between 0.1 and 1 U/ml. Quinacrine, a PLA2 inhibitor, suppressed the thrombin-induced AA release. In addition, quinacrine also suppressed the thrombin-induced prostaglandin E2 synthesis in these cells. On the other hand, propranolol, which is known to inhibit phosphatidic acid phosphohydrolase, did not affect the thrombin-induced AA release. ...
Purified human monocytes release and metabolize endogenous arachidonic acid (20:4) from phospholipid stores when challenged with particulate inflammatory stimuli or the calcium ionophore A23187. Using radiolabeled cultures, the percentage of total [3H]20:4 released was similar with each type of stimulus. However, the spectrum of 20:4 metabolites differed. With opsonized zymosan (OpZ) or Sephadex beads coated with IgG immune complexes (Ig-beads), the predominant product was thromboxane (25% of the total) together with smaller amounts of other cyclo-oxygenase products and lipoxygenase metabolites. Levels of thromboxane synthesis by monocytes were comparable to those by platelets, as measured by radioimmunoassay. In contrast, exposure to the nonspecific agent A23187 led to mainly lipoxygenase products (70% of the total). Monocytes isolated from mononuclear cell fractions of peripheral blood contain platelets specifically rosetted to their surfaces. These platelet contaminants were removed by ...
Arachidonic acid may trigger brain inflammation. High blood levels have been associated with a greater risk of suicide and depressive episodes. On the other hand, diets high in carbohydrate and low in fat and protein (with little or no arachidonic acid) may be associated with lower levels of anxiety and depression, according to epidemiological studies.. In one study, overweight or diabetic employees who went on a whole food, plant-based diet reported increased energy, better sleep patterns and improved mental health compared to a control group given no diet restrictions. Their work productivity also showed improvement.. A similar subsequent study of employees at 10 corporate sites showed notable improvements in depression, anxiety and emotional well-being among those following a meat-free, plant-based diet.. ...
Fas-mediated apoptosis of human leukemic U937 cells was accompanied by increased arachidonic acid (AA) and oleic acid release from membrane glycerophospholipids, indicating phospholipase A2 (PLA2) activation. During apoptosis, type IV cytosolic PLA2 (cPLA2), a PLA2 isozyme with an apparent molecular mass of 110 kDa critical for stimulus-coupled AA release, was converted to a 78-kDa fragment with concomitant loss of catalytic activity. Cleavage of cPLA2 correlated with increased caspase-3-like protease activity in apoptotic cells and was abrogated by a caspase-3 inhibitor. A mutant cPLA2 protein in which Asp522 was replaced by Asn, which aligns with the consensus sequence of the caspase-3 cleavage site (DXXD downward arrowX), was resistant to apo-ptosis-associated proteolysis. Moreover, a COOH-terminal deletion mutant of cPLA2 truncated at Asp522 comigrated with the 78-kDa fragment and exhibited no enzymatic activity. Thus, caspase-3-mediated cPLA2 cleavage eventually leads to destruction of a catalytic
TY - JOUR. T1 - Cyclooxygenase-2-mediated metabolism of arachidonic acid to 15-oxo-eicosatetraenoic acid by rat intestinal epithelial cells. AU - Seon, Hwa Lee. AU - Rangiah, Kannan. AU - Williams, Michelle V.. AU - Wehr, Angela Y.. AU - DuBois, Raymond N.. AU - Blair, Ian A.. PY - 2007/11. Y1 - 2007/11. N2 - Rat intestinal epithelial cells mat permanently express the cyclooxygenase-2 (COX-2) gene (RIES cells) were used to investigate COX-2-mediated arachidonic acid (AA) metabolism. A targeted chiral lipidomics approach was employed to quantify AA metabolites that were secreted by the cells into the culture media. When intact RIES cells were treated with calcium ionophore A-23187 (1 μM) for 1 h, 11-(R)-hydroxyeicosatetraenoic acid (HETE) was the most abundant metabolite, followed by prostaglandin (PG) E2, 15-(S)-HETE, 15-oxo-eicosatetraenoic acid (ETE), and 15-(R)-HETE. Incubation for a further 23 h after the calcium ionophore was removed resulted in a substantial increase in PGE2 ...
A complex structurally diverse series of eicosanoids arises from the metabolism of arachidonic acid. The metabolic profile is further complicated by the enantioselectivity of eicosanoid formation and the variety of regioisomers that arise. In order to investigate the metabolism of arachidonic acid in vitro or in vivo, targeted methods are advantageous in order to distinguish between the complex isomeric mixtures that can arise by different metabolic pathways. Over the last several years this targeted approach has become more popular, although there are still relatively few examples where chiral targeted approaches have been employed to directly analyze complex enantiomeric mixtures. To efficiently conduct targeted eicosanoid analyses, LC separations are coupled with collision induced dissociation (CID) and tandem mass spectrometry (MS/MS). Product ion profiles are often diagnostic for particular regioisomers. The highest sensitivity that can be achieved involves the use of selected reaction monitoring
The prostaglandins (PG) are a group of physiologically active lipid compounds called eicosanoids[1] having diverse hormone-like effects in animals. Prostaglandins have been found in almost every tissue in humans and other animals. They are derived enzymatically from the fatty acid arachidonic acid.[2] Every prostaglandin contains 20 carbon atoms, including a 5-carbon ring. They are a subclass of eicosanoids and of the prostanoid class of fatty acid derivatives. The structural differences between prostaglandins account for their different biological activities. A given prostaglandin may have different and even opposite effects in different tissues in some cases. The ability of the same prostaglandin to stimulate a reaction in one tissue and inhibit the same reaction in another tissue is determined by the type of receptor to which the prostaglandin binds. They act as autocrine or paracrine factors with their target cells present in the immediate vicinity of the site of their secretion. ...
Fat is back. Not that it ever really went away. Even when very low-fat diets were all the rage, experts recognized that certain fats were more harmful than others and some were even beneficial.. A common misperception is that omega-6 polyunsaturated fats, which are found in abundant amounts in most oils, including soybean oil, are pro-inflammatory. Meanwhile, it is thought that omega-3 polyunsaturated fats protect against inflammation. Chronic inflammation is believed to be a key process underlying many chronic diseases.. Back in the late 1970s, researchers suggested that the low incidence of heart disease among the Inuit of Canada and Alaska was related to their fat intake.1 Specifically, this population eats a diet high in the omega-3 fatty acid eicosanoic acid from fish and low in the omega-6 fatty acid arachidonic acid which is found in other types of meat.. The findings put omega-3 fats in the spotlight, giving rise to the popularity of fish oil supplements. But evidence in support of the ...
BioAssay record AID 3623 submitted by ChEMBL: Inhibition of [14C]arachidonic acid conversion to 5-HETE by broken cell 5-LO isolated from guinea pig PMN.
In the present study, we investigated whether the protective effect of FK506 and cyclosporin A (CsA) against in vitro ischemic injury of astrocytes might be mediated through attenuation of cytosolic isoform of phospholipase A(2) (cPLA(2)) expression and activity as well as inhibition of arachidonic acid (AA) release. On the 21st day in vitro, cultures of rat astrocytes were subjected to ischemia-simulating conditions (combined oxygen glucose deprivation) for 8 h and exposed to FK506 (10 - 1,000 nM) and CsA (0.25 - 10 microM). Obtained data suggest the cross-talk between the action of 0.25 - 10 microM CsA as well as 1 microM FK506 on calcineurin (CaN) and cPLA(2) in anti-apoptotic signal transduction pathways. Moreover, we have shown that immunosuppressants at these concentrations protected glial cells against ischemia-induced apoptosis through the increase of cell viability, mitochondrial function restoration, and attenuation of oxidative stress. Finally, in our study, low concentrations of FK506 (10
Topical corticosteroids and topical nonsteroidal antiinflammatory drugs (NSAIDs) are the two main options at surgeons disposal for controlling postoperative ocular inflammation. While both drug classes decrease inflammation, they have different properties and different mechanisms of action.Steroids block the inflammatory cascade at an early stage: the arachidonic acid pathway activated by tissue damage. But to be effective, steroids need to pass through cell membranes and enter the nucleus, which is limited because of their lipophobic nature. In addition, steroid side effects include intraocular pressure (IOP) elevation, delayed wound healing, and increased susceptibility to infection.NSAIDs block cyclooxygenase (COX-1 and COX-2), enzymes that convert arachidonic acid into the prostaglandins that directly mediate inflammation. NSAIDs enter cells readily and effectively shut down prostaglandin formation; within its class, the brominated NSAID bromfenac penetrates cells particularly well. ...
Prostaglandins act as short-lived localized hormones that can be released by any cell of the body during tissue, chemical, or traumatic injury, and can induce fever, inflammation, and pain, once they are present in the intercellular space. Thromboxanes, which are also hormone activators, can regulate blood vessel tone, platelet aggregation, and clot formation to increase the inflammatory response.[92,82] The inflammatory pathway is a complex biochemical pathway which, once stimulated by injury, leads to the production of these and other inflammatory mediators whose initial effect is pain and tissue destruction, followed by healing and recovery.[34,51] A major component of the inflammatory pathway is called the arachidonic acid pathway because arachidonic acid is immediately released from traumatized cellular membranes. Membrane-based arachidonic acid is transformed into prostaglandins and thromboxanes partly through the enzymatic action of cyclooxygenase (COX)[34,57]. There are two types of COX ...
Prostaglandins act as short-lived localized hormones that can be released by any cell of the body during tissue, chemical, or traumatic injury, and can induce fever, inflammation, and pain, once they are present in the intercellular space. Thromboxanes, which are also hormone activators, can regulate blood vessel tone, platelet aggregation, and clot formation to increase the inflammatory response.[92,82] The inflammatory pathway is a complex biochemical pathway which, once stimulated by injury, leads to the production of these and other inflammatory mediators whose initial effect is pain and tissue destruction, followed by healing and recovery.[34,51] A major component of the inflammatory pathway is called the arachidonic acid pathway because arachidonic acid is immediately released from traumatized cellular membranes. Membrane-based arachidonic acid is transformed into prostaglandins and thromboxanes partly through the enzymatic action of cyclooxygenase (COX)[34,57]. There are two types of COX ...
The primary American source of dietary arachidonic acid is eating meat. Meat is not bad per se. Meat becomes bad when the animal is fed junk food that makes it fat and sick. Economically, our food animals are fed the food that is most fattening. Thats because they are sold by the pound. Fatter animals are worth more in the marketplace. Our food animals are proven to become really fat on a diet of corn and/or soybeans.. Of course, fattening animal feed is a poor economic choice unless it is also cheap feed. In todays political environment, the cheapest feed is the food that is subsidized by the taxpayers; and it makes so much sense: lobbying our politicians to use taxpayer dollars to grow corn and soybeans creates a win-win situation for all, cheap meat (this is sarcasm, as noted below).. Meat, a source of complete proteins, historically was an expensive and therefore rare commodity (at least since the Agricultural Revolution, beginning about 10,000 years ago). Animals become big and fat on a ...
BioAssay record AID 274914 submitted by ChEMBL: Activity at COX1 assessed as inhibition of arachidonic acid-induced PGE2 production in J774 cells at 0.01 uM.
just read a article about arachidonic acid,,,had sum great info on it,,,,was wondering if anyone here uses it while on / off cycle and does it really work or is
In addition to conventional treatment, there are also nutritional means to deal with inflammation. In my practice, I have helped many individuals complaining of pain from various itis diseases. We address the source of the inflammation, rather than attempting to inhibit an enzyme. The real problem may be the over-abundance of Arachidonic acid that is available to enter the PGE2 inflammatory pathway. Therefore, the first step should be to reduce the dietary consumption of Arachidonic acid, which is only found in animal products. Secondly, supplementing with the omega3 fatty acids, such as DHA and EPA, commonly found in fish oil is also beneficial. One important role of omega3 fatty acids is to keep Arachidonic acids from escaping from our own cell membranes. This may account for the anti-inflammatory role that omega three fatty acids are credited with. I have even seen dramatic results when fish oil is used topically over an inflamed area. For example, many have found relief from the pain ...
This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This protein localizes to the endoplasmic reticulum and is thought to be the predominant enzyme responsible for epoxidation of endogenous arachidonic acid in cardiac tissue. Multiple transcript variants have been found for this gene. [provided by RefSeq, Jan 2016 ...
In contrast with mammalian cells, little is known about the control of Ca2+ entry into primitive protozoans. Here we report that Ca2+ influx in pathogenic Trypanosoma brucei can be regulated by phospholipase A2 (PLA2) and the subsequent release of arachidonic acid (AA). Several PLA2 inhibitors blocked Ca2+ entry; 3-(4-octadecyl)-benzoylacrylic acid (OBAA; IC50 0.4+/-0.1 microM) was the most potent. We identified in live trypanosomes PLA2 activity that was sensitive to OBAA and could be stimulated by Ca2+, suggesting the presence of positive feedback control. The cell-associated PLA2 activity was able to release [14C]AA from labelled phospholipid substrates. Exogenous AA (5-50 microM) also initiated Ca2+ entry in a manner that was inhibited by the Ca2+ antagonist La3+ (100 microM). Ca2+ entry did not depend on AA metabolism or protein kinase activation. The cell response was specific for AA, and fatty acids with greater saturation than tetraeicosanoic acid (AA) or with chain lengths less than C20 ...
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Arachidonic Acids Role in Stress and Shock April 3, 2012 Posted in General.. Comments Off on Arachidonic Acids Role in Stress and Shock ...
Series three - made from EPA. The number one function of series 3 prostaglandins is to save you Arachidonic Acid release from cells.. Arachidonic Acid passing thru this pathway will increase irritation and the other problems noted in Series 2. Anything we will do to decrease interest because of the AA pathway is beneficial.. Remember that Omega-threes & Omega-6s can undergo the equal pathway. The Omega-3s are transformed at a lower charge resulting in a decrease quantity. The merchandise of this pathway are then degraded by enzymes.. This machine, like many in the frame, is in constant stability. However, once in a while the manufacturing exceeds metabolism resulting in accelerated inflammation. Omega-3s are inflammatory but to a lesser quantity. Additionally, theyre produced slower ensuing in fewer numbers. This is one of the many blessings of Omega-three fatty acids.. ...
A compound of the formula ##STR1## wherein n is an integer from 2 to 4; m is an integer from 3 to 5; R is OM, OR1 or NR2 R3 where M is a pharmaceutically acceptable cation; R1, R2 and R3 are the same or different and selected from the group consisting of hydrogen, C1 -C12 branched, unbranched or cyclic alkyl, aryl and aralkyl; or R2 and R3 taken together form a group of the formula ##STR2## can be used as an inhibitor of the lipoxygenase pathway of the arachidonic acid cascade in animals.
Principal Investigator:MAIZUMI Yuji, Project Period (FY):1998 - 1999, Research Category:Grant-in-Aid for Scientific Research (C), Section:一般, Research Field:Biological pharmacy
Scientists in Cambridge have discovered that a brain protein called syntaxin enables fatty molecules, used widely in health supplements, to work in the brain to make it function properly. Lead Scientist, Dr Bazbek Davletov and his colleague Dr Colin Rickman from the Medical Research Council (MRC) Laboratory of Molecular Biology in Cambridge, UK report their findings in the journal Chemistry and Biology.. ...
Dumex Dulac Boouc 1 information about active ingredients, pharmaceutical forms and doses by Danone, Dumex Dulac Boouc 1 indications, usages and related health products lists
AuxInfo=1/1/N:1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22/E:(21,22)/rA:22nCCCCCCCCCCCCCCCCCCCCOO/rB:s1;s2;s3;s4;s5;d6;s7;s8;d9;s10;s11;d12;s13;s14;d15;s16;s17;s18;s19;s20;d20;/rC:-7.3658,-.6188,0;-6.6513,-.2062,0;-5.9368,-.6188,0;-5.2224,-.2062,0;-4.5079,-.6188,0;-3.7934,-.2062,0;-2.9684,-.2062,0;-2.2539,-.6188,0;-1.5395,-.2062,0;-.7145,-.2062,0;0,-.6188,0;.7145,-.2062,0;1.5395,-.2062,0;2.2539,-.6188,0;2.9684,-.2062,0;3.7934,-.2062,0;4.5079,-.6188,0;5.2224,-.2062,0;5.9368,-.6188,0;6.6513,-.2062,0;7.3658,-.6188,0;6.6513,.6188,0 ...
EaseFlex PLUS Chews with Green Lipped Mussel supplementation is for the ageing dog or active youngster that has loss of mobility through reduced joint function with Omega-3 Polyunsaturated Fatty Acids (PUFAs) which structurally mimic Arachidonic Acid metabolites.
Thromboxane A2 (TXA2) is an arachidonic acid metabolite that is released during tissue trauma and elicits platelet aggregation and vascular smooth muscle contraction. Previous research has shown that TXA2 stimulates pulmonary ...
(2011) Ugajin et al. American Journal of Pathology. Prostaglandin (PG) D2 and PGE2 are arachidonic acid metabolites that are generated though an isomerization reaction catalyzed by PG synthases. PGs have been implicated in immunologic reactions in addition to a wide range of physiological functio...
CYCLOOXYGENASE-2: Cyclooxygenase (COX), first purified in 1976 and cloned in 1988, is the key enzyme in the synthesis of prostaglandins (PGs) from arachidonic acid. In 1991, several laboratories identified a product from a second gene with COX activity and called it COX-2. However, COX-2 was inducible, and the inducing stimuli included pro-inflammatory cytokines and growth factors, implying a role for COX-2 in both inflammation and control of cell growth. The two isoforms of COX are almost identical in structure but have important differences in substrate and inhibitor selectivity and in their intracellular locations. Protective PGs, which preserve the integrity of the stomach lining and maintain normal renal function in a compromised kidney, are synthesized by COX-1. In addition to the induction of COX-2 in inflammatory lesions, it is present constitutively in the brain and spinal cord, where it may be involved in nerve transmission, particularly that for pain and fever. PGs made by COX-2 are ...
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The present study investigated the role of arachidonic acid and acetylcholine in mediating endothelium-dependent relaxations of rabbit aorta. Isolated thoracic aortic rings were precontracted with a submaximal concentration of norepinephrine, and the effect of various agents on arachidonic acid- and acetylcholine-induced relaxations was examined. Arachidonic acid elicited a concentration-related relaxation that was potentiated by the cyclooxygenase inhibitor indomethacin. Treatment with the lipoxygenase inhibitor nordihydroguaiaretic acid completely blocked but the cytochrome P450 inhibitor metyrapone had no effect on arachidonic acid-induced relaxation. NG-Monomethyl-L-arginine and nitro-L-arginine, compounds that inhibit the nitric oxide-like endothelium-derived relaxing factor, had little or no effect on arachidonic acid-induced relaxations. In contrast, nordihydroguaiaretic acid, metyrapone, NG-monomethyl-L-arginine, and nitro-L-arginine all attenuated the relaxation to acetylcholine; ...
The physiological roles of highly unsaturated fatty acids (HUFA), mainly arachidonic acid (AA, 20:4ω6) and docosahexaenoic acid (DHA, 22:6ω3), are not completely understood. In order to study specific functions for AA and DHA, a delta-6 desaturase knockout (D6D-/-) mouse was created. D6D is a key enzyme in synthesizing HUFA from the precursor dietary essential fatty acids, linoleic acid (LA, 18:2ω6) or α-linolenic acid (ALA, 18:3ω3). By disrupting D6D expression, LA and ALA provided in the diet will not be metabolized to HUFA. Phenotype of the D6D-/- mouse is therefore specific to lack of AA and/or DHA and consists of ulcerative dermatitis, male infertility, gastrointestinal ulcers, and hepatic lipidosis. New insight on specific AA and DHA roles was established through dietary prevention of HUFA deficiency phenotype. The absence of a D6D isozyme had to be assessed before further characterizing HUFA roles with the D6D-/- mouse model. The presence of a D6D isozyme would interfere with the ...
1. Since ageing has been associated with a decrease in both immune responses and antioxidant defences, this study was undertaken to compare the glutathione peroxidase activity in peripheral blood mononuclear cells of healthy elderly and young donors. The mean value of glutathione peroxidase activity was significantly lower in the aged group (−36%) than that observed in the young control group (n = 10).. 2. This defect was accompanied by a marked increase (+106%) in the oxygenated metabolism of endogenous arachidonic acid by lipoxygenases as judged by the radiolabel associated with hydroxyeicosatetraenoic acids in [3H]arachidonic acid-prelabelled peripheral blood mononuclear cells, whereas the cyclo-oxygenase activity, estimated by the radiolabel associated with thromboxane B2, was not significantly altered.. 3. Upon stimulation by the mitogenic lectin concanavalin A, the radioactivity associated with total eicosanoids (free arachidonic acid plus hydroxyeicosatetraenoic acids plus thromboxane ...
TY - JOUR. T1 - Candida albicans stimulates arachidonic acid liberation from alveolar macrophages through α-mannan and β-glucan cell wall components. AU - Castro, M.. AU - Ralston, N. V C. AU - Morgenthaler, Timothy Ian. AU - Rohrbach, M. S.. AU - Limper, Andrew Harold. PY - 1994. Y1 - 1994. N2 - Candida albicans is an increasingly important fungal pathogen. Alveolar macrophages respond to fungal components such as zymosan by releasing arachidonic acid (AA) and AA metabolites. However, few studies have evaluated the effect of whole fungi on macrophage eicosanoid metabolism. We hypothesized that macrophages respond to C. albicans by releasing AA and generating AA metabolites as a consequence of interaction of mannose and β- glucan receptors with fungal cell wall components. [14C]AA-labeled rabbit alveolar macrophages released AA following stimulation with either live or heat-killed C. albicans. High-pressure liquid chromatography analysis revealed that 55% of the AA released was metabolized ...
The effect of ethanol feeding on the essential fatty acid content of tissues has been contradictory. To define the effect, we analyzed fatty acid profiles in various tissues from five miniature pigs fed daily 105 kJ basal diet/kg body wt and 146 kJ e
A recognized feature of psoriasis and other proliferative dermatoses is accumulation in your skin from the unusual arachidonic acidity metabolite, 12hydrogen through the 10-carbon of arachidonate. included regions of epidermis in psoriasis possess PPARG improved concentrations of free of charge arachidonic acid and 12-HETE markedly. Chiral analysis from the 12-HETE in psoriasis revealed that the major enantiomer is 12390C404, encompassing the major M-PFB ions at 391 (unlabeled HETE) and 399 (d8 analogue), essentially as described previously (28). Experiments with Stereospecifically Labeled Arachidonic Acids. The specific activities of the two 10-3H-labeled arachidonic acids were approximately 10,000C20,000 disintegrations per min 3H per g. The pro-[10-3H]arachidonic acid was enriched in tritium by incubation with an 8as described in principle before (29). The stereospecifically labeled arachidonic acids were admixed with [14C]arachidonic acid, which served as an internal standard for measurement ...
Arachidonate metabolites are important regulators of human breast cancer cells. Production of bioactive lipids are frequently initiated by the enzyme phospholipase A2 which releases arachidonic acid (AA) that is rapidly metabolized by cyclooxygenases (COX) or lipoxygenases (LO) to other highly potent lipids. In this study we screened a number of inhibitors which blocked specific pathways of AA metabolism for their antiproliferative activity on MCF-7 wild type and MCF-7 ADR drug resistant breast cancer cells. The toxicity of these inhibitors was further tested on human bone marrow cell proliferation. Inhibitors of LO pathways (specifically the 5-LO pathway) were most effective in blocking proliferation. Inhibitors of platelet activating factor, a byproduct of arachidonate release, were also effective antiproliferative agents. Curcumin, an inhibitor of both COX and LO pathways of eicosanoid metabolism, was 12-fold more effective in blocking proliferation of the MCF-7 ADRs cells compared to MCF-7 wild type
The phorbol ester tumor promoter (12-0-tetradecanoyl-phorbol-13-acetate (10-7-10-9 M) caused a rapid (1-3 hr after addition) release of arachidonic acid and prostaglandins E2 and F2α from chick embryo fibroblasts. This effect was inhibited by cycloheximide and puromycin. Prostaglandin release was more sensitive to inhibition than was arachidonic acid release. Indomethacin, a cyclooxygenase inhibitor, completely blocked TPA-induced prostaglandin synthesis and slightly enhanced arachidonic acid release. Despite the complete suppression of prostaglandin synthesis, indomethacin caused only a 20-30% inhibition of TPA induction of plasminogen activator. Phorbol 12,13-didecanoate, phorbol-l2,13-dibenzoate and mezerein were also potent inducers of arachidonic acid and prostaglandin release, while phorbol and 4α phorbol didecanoate were inactive. All trans retinoic acid (10-5-10-6 M) inhibited TPA-induced arachidonic acid and prostaglandin release; retinyl palmitate and β-carotene were less effective ...
The Brain Physiology and Metabolism Section (BPMS) of the National Institute on Aging (NIA) and the Clinical Neuroscience Program (CNP) of the National Institute of Neurological Disorders and Stroke (NINDS) propose to study regional brain phospholipid metabolism in young and old normal volunteers and in patients with Alzheimer disease. The method to be employed, developed from animal studies, involves the intravenous injection of a radiolabeled polyunsaturated fatty acid, [11C]arachidonic acid and measuring regional brain radioactivity using positron emission tomography (PET). A mathematical model is used to calculate regional brain incorporation coefficients k* of [11C]arachidonate into brain. These reflect brain signal transduction and membrane turnover involving phospholipids and the signal transduction and membrane turnover involving phospholipids and the activation of the enzyme, phospholipase A2. PET also will be used in the same subjects to measure regional cerebral blood flow (rCBF), a ...
The Brain Physiology and Metabolism Section (BPMS) of the National Institute on Aging (NIA) and the Clinical Neuroscience Program (CNP) of the National Institute of Neurological Disorders and Stroke (NINDS) propose to study regional brain phospholipid metabolism in young and old normal volunteers and in patients with Alzheimer disease. The method to be employed, developed from animal studies, involves the intravenous injection of a radiolabeled polyunsaturated fatty acid, [11C]arachidonic acid and measuring regional brain radioactivity using positron emission tomography (PET). A mathematical model is used to calculate regional brain incorporation coefficients k* of [11C]arachidonate into brain. These reflect brain signal transduction and membrane turnover involving phospholipids and the signal transduction and membrane turnover involving phospholipids and the activation of the enzyme, phospholipase A2. PET also will be used in the same subjects to measure regional cerebral blood flow (rCBF), a ...
The cooxidative metabolism of the urinary bladder carcinogen benzidine was examined using renal inner medullary microsomes. The products of [14C]benzidine metabolism were recovered in the aqueous but not in the organic soluble fraction of reaction mixtures. The reactive metabolites formed during cooxidative metabolism of benzidine bound to DNA and transfer RNA. Cooxidative metabolism of benzidine and subsequent binding to nucleic acids was dependent upon specific fatty acid substrates and was blocked by inhibitors of prostaglandin endoperoxide synthetase. The ratio of the rates of benzidine product formation was approximately 10:3:1 (trichloroacetic acid precipitable:non-trichloroacetic acid precipitable:transfer RNA bound) over a wide range of arachidonic acid concentrations. Cumene hydroperoxide also initiated cooxidative metabolism of benzidine but was less effective than was arachidonic acid. In contrast to arachidonic acid, cumene hydroperoxide-mediated metabolism of benzidine and guaiacol ...
Interest in the modulation of renal diseases by polyunsaturated fatty acids (PUFA) led this group to examine the effects of borage oil (BO) and corn oil (CO) in the rat 5/6-renal-ablation model. BO is a rich source of gamma-linolenic acid (GLA; 18:3n
Our previous studies suggested that enhanced pulmonary artery contractions to arachidonic acid in females compared with males were mediated by an LO metabolite.6 The purpose of the current study was to systematically characterize the LO pathways in female and male pulmonary arteries. First, it was shown that the protein expression of both 15- and 5-LO was greater in females compared with males. Although pulmonary arteries from both male and females produced the corresponding LO metabolites, 15- and 5-HETE, only the synthesis of 15-HETE was enhanced in females. The increase in 15-HETE was correlated with an increased 15-HETE-mediated pulmonary artery vasoconstriction in females compared with males. These findings are significant because it is the first report that the 15-LO pathway is regulated in a sex-specific way. These results may impact what is known about the sex differences in the incidence of PAH.. The enhanced vasoconstriction in females compared with males could be because of increased ...
Effect of docosapentaenoic acid (DPA) on arachidonic acid (AA) stimulated production of MMP-9. MonoMac 6 cells (0.8 × 106 cells/ml in X-Vivo 15) were incubated
In the present study, we demonstrate that both native and synthetic Pardaxin trigger the AA cascade in PC12 cells. This stimulation is mediated by activation of PLA2, as reflected in the massive release of AA and various eicosanoids. Stimulation of the AA cascade in PC12 cells by Pardaxin was blocked by a variety of AA cascade inhibitors.. The activation of cellular phospholipases is thought to mediate signal transduction of certain receptors, and it has been related to a variety of cellular events (Serhan et al., 1996). A moderate increase in AA release is observed after receptor-mediated PLA2 activation by different ligands such as nerve growth factor (Fink and Guroff, 1990), ACh (Felder et al., 1990a), serotonin (Felder et al., 1990b), histamine (Murayamaet al., 1990), bradykinin (Allen et al., 1992) and epidermal growth factor (Schalkwijk et al., 1995). In the present study, we found that Pardaxin-induced AA release in PC12 cells was up to 10-fold greater than that in the control. Such ...
Cytosolic phospholipase A2 is an enzyme that in humans is encoded by the PLA2G4A gene. This gene encodes a member of the cytosolic phospholipase A2 group IV family. The enzyme catalyzes the hydrolysis of membrane phospholipids to release arachidonic acid which is subsequently metabolized into eicosanoids. Eicosanoids, including prostaglandins and leukotrienes, are lipid-based cellular hormones that regulate hemodynamics, inflammatory responses, and other intracellular pathways. The hydrolysis reaction also produces lysophospholipids that are converted into platelet-activating factor. The enzyme is activated by increased intracellular Ca2+ levels and phosphorylation, resulting in its translocation from the cytosol and nucleus to perinuclear membrane vesicles. PLA2G4A has been shown to interact with HTATIP. Mutations in this gene have been associated with multifocal stenosing ulceration of the small intestine. GRCh38: Ensembl release 89: ENSG00000116711 - Ensembl, May 2017 GRCm38: Ensembl release ...
Yau, T M. and Sun, G Y., "The metabolism of (1-14c)arachidonic acid in the neutral glycerides and phosphoglycerides of mouse brain." (1974). Subject Strain Bibliography 1974. 89 ...
Lipoxygenases (LOs) constitute a heterogeneous family of enzymes that catalyze the stereoselective dioxygenation of polyunsaturated fatty acids to their corresponding hydroperoxy derivatives.1,2 In mammals, LOs are categorized with respect to their positional specificity of arachidonic acid oxygenation into 5-, 8-, 12-, and 15-LOs.1-3 These enzymes induce structural and metabolic changes in cells during a wide variety of physiological and pathological processes, such as differentiation, carcinogenesis, inflammation, and atherogenesis. Accumulating studies have suggested diverse and opposing roles for the various LO pathways in the pathogenesis of human diseases, particularly cancer and atherosclerosis.2-5 Consistent with the existence of multiple isoforms of LOs, a variety of intermediate and end products of arachidonic acids are found in various cell types, and they in turn activate diverse signaling cascades, resulting in diverse outcomes. Therefore, sophisticated understanding of the ...
Non-heme iron-containing dioxygenase that catalyzes the stereo-specific peroxidation of free and esterified polyunsaturated fatty acids generating a spectrum of bioactive lipid mediators. Mainly converts arachidonic acid to (12R)-hydroperoxyeicosatetraenoic acid/(12R)-HPETE and minor stereoisomers. In the skin, acts upstream of ALOXE3 on the lineolate moiety of esterified omega-hydroxyacyl-sphingosine (EOS) ceramides to produce an epoxy-ketone derivative, a crucial step in the conjugation of omega-hydroxyceramide to membrane proteins. Therefore plays a crucial role in the synthesis of corneocytes lipid envelope and the establishment of the skin barrier to water loss. May also play a role in the regulation of the expression of airway mucins ...
BECA, T; HERNANDEZ, G y BASCONES, A. NSAIDs in the treatment of periodontal disease. Avances en Periodoncia [online]. 2007, vol.19, n.2, pp.101-113. ISSN 2340-3209.. SUMMARY A review about the application of antiinflammatories as an aid for the periodontal treatment is presented. After a brief introduction, we explain the immunological bases of periodontal inflamation and tissue destruction, focusing on arachidonic acid metabolism and the four most important inflammatory mediators now in periodontal tissue resorption: prostaglandin E2 (PGE2), prostaglandin F2a(PGF2a), leucotriene B4 (LTB4) and platelet activation factor (PAF), and explaining their actions and role in inflammation through matrix metalloproteinase (MMPs) and their relation with some other mediators in the inflammatory chain also related with tissue resorption. After, we expound some of the most used drugs for the inhibition of all of these mediators (non-steroid antiinflammatory drugs or NSAIDs, omega3 fatty acids, tetracyclines ...
We have recently reported that cyclooxygenase (COX)-2-deficiency affects brain upstream and downstream enzymes in the arachidonic acid (AA) metabolic pathway to prostaglandin E2 (PGE2), as well as enzyme activity, protein and mRNA levels of the reciprocal isozyme, COX-1. To gain a better insight into the specific roles of COX isoforms and characterize the interactions between upstream and downstream enzymes in brain AA cascade, we examined the expression and activity of COX-2 and phospholipase A2 enzymes (cPLA2 and sPLA2), as well as the expression of terminal prostaglandin E synthases (cPGES, mPGES-1, and − 2) in wild type and COX-1-/- mice. We found that brain PGE2 concentration was significantly increased, whereas thromboxane B2 (TXB2) concentration was decreased in COX-1-/- mice. There was a compensatory up-regulation of COX-2, accompanied by the activation of the NF-κB pathway, and also an increase in the upstream cPLA2 and sPLA2 enzymes. The mechanism of NF-κB activation in the ...
Mamil Nite Special Formula information about active ingredients, pharmaceutical forms and doses by Dumex, Mamil Nite Special Formula indications, usages and related health products lists
Now that you understand the mechanism of chemotherapys actions, we can better deal with its side effects. Starting with a proper nutritional foundation can help the body to better cope with illness. Tumor cells are very active metabolically and most of their energy requirements are diverted to the sole purpose of mitosis (cell division). A source of quick energy for tumor cells is provided by glucose. That explains why tumor cells are voracious sugar feeders. Another nutrient they need is fat, in the form of fatty acids, to maintain the structure of their cell membranes. An omega-6 fatty acid called arachidonic acid is particularly essential to tumor cells. Since they lack the enzyme to synthesize it, tumor cells may obtain it from your dietary intake. Arachidonic acid is found in animal products. If this fatty acid is not provided, tumor cells must substitute other forms of fatty acids from the omega-6 family. This can result in a weakened tumor cell membrane that may be less resistant to drug ...
Arachidonic Acid, Phospholipase, Cells, Coa, Mass Spectrometry, Phospholipids, Spectrometry, Macrophages, Inhibition, Acyltransferases, Eicosanoids, Glycerophospholipids, Human, Monocytes, Phospholipase A2, Zymosan, Choline, Phosphatidylinositol, Calcium, Innate Immune Responses
Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a receptor for prostaglandin E2, a metabolite of arachidonic acid which has different biologic activities in a wide range of tissues. Mutations in this gene are associated with aspirin-induced susceptibility to asthma. [provided by RefSeq, Oct 2009 ...
Why do people who eat more plants get less cancer? The largest prospective study of diet and cancer in history, for example, found that vegetarians had lower levels of all cancers combined. This could be due to what they eat less of: animal protein arachidonic acid endotoxins heme iron heterocyclic amines industrial
TY - JOUR. T1 - Arachidonic acid inhibits luteinizing hormone-stimulated progesterone production in hen granulosa cells. AU - Johnson, A. L.. AU - Tilly, J. L.. PY - 1990/1/1. Y1 - 1990/1/1. N2 - Arachidonic acid has been proposed to function as a hormone-induced second messenger in a variety of mammalian endocrine tissues. The present studies were conducted to evaluate whether arachidonic acid, either added exogenously or released endogenously following treatment with physiologic (phospholipase A2) or pharmacologic (melittin) agents, influences basal and/or luteinizing hormone (LH)-induced cyclic adenosine 3,5-monophosphate (cAMP) and progesterone production in granulosa cells from domestic hens. Phospholipase A2 (PLA2) and melittin treatments failed to alter basal concentrations of progesterone, whereas arachidonic acid had a slight stimulatory effect (only at the 50-μM dose) on progesterone levels, and no effect on cAMP. By contrast, arachidonic acid, PLA2, and melittin each inhibited ...
Arachidonic acid is arguably the most important PUFA associated with membrane phospholipids. Upon release, AA can be enzymatically metabolized to a myriad of bioactive derivatives, eicosanoids, known to contribute to a variety of chronic diseases, but are also known to be involved in tissue homeostasis and the resolution of inflammation [1-4, 22]. The relative abundance of AA in membrane phospholipids positively influences eicosanoid production [23]. It is well known that dietary PUFA can affect tissue AA levels; however, what is uncertain and controversial is whether modifying current intakes of dietary LA will result in concomitant changes in tissue AA content, i.e., increasing LA intake results in an increase in tissue AA content and decreasing LA has the opposite effect [8]. The goal of this paper was to ascertain the relationship between dietary LA and tissue AA content (phospholipid pools of plasma/serum and erythrocytes) in adults consuming a Western-style background diet. It was not ...
TY - JOUR. T1 - Chronic exposure to sidestream smoke adversely alters 14C-(AA) arachidonic acid metabolism in platelets and aortas from rats. AU - Lubawy, W. C.. AU - Valentovic, M. A.. PY - 1984/1/1. Y1 - 1984/1/1. UR - http://www.scopus.com/inward/record.url?scp=0021149080&partnerID=8YFLogxK. M3 - Article. AN - SCOPUS:0021149080. VL - 43. SP - no. 2785. JO - Federation Proceedings. JF - Federation Proceedings. SN - 0014-9446. IS - 3. ER - ...
LIQUID CHROMATOGRAPHY-MASS SPECTROMETRY FOR THE STUDY OF ARACHIDONIC ACID METABOLITES Xiaojing Liu Ian A. Blair, PhD Arachidonic acid (AA) oxidation metabolism has been an important research topic for decades, and numerous oxidation products as well as enzymes involved in AA metabolism together with their downstream metabolites have been identified, although unknown pathways still remain to be characterized. In the present a study a new AA metabolite, 11-oxo-eicosatetraenoic acid (ETE), generated from a major product of cyclooxygenase (COX-2), 11(R)-hydroxyeicosatetraenoic acid (HETE), through 15-hydroxyprostaglandine dehydrogenase (15-PGDH)-mediated oxidation. 11-Oxo-ETE was found to have an anti-proliferative effect on human umbilical vein endothelial cells (HUVECs), with a similar IC50 to a well- known anti-inflammatory mediator, 15-deoxy-12,14-prostaglandin J2 (15d-PGJ2). It was also found that 11-oxo-ETE could be inactivated through the glutathione-S-transferase (GST)/glutathione (GSH) pathway
Eicosanoids are lipid mediators synthesized by the arachidonic acid (AA) cascade from membrane polyunsaturated fatty acids (PUFA) trough three distinct pathways: cyclooxygenase, lipooxygenase (LOX) and cytochrome P450 pathways. Eicosapentaenoic acid, an n-3 PUFA, is also substrate of the enzymes of the AA cascade. Thus, 5-LOX gives rise to the 5-series leukotrienes, and 12-LOX generates 12-HEPE, the homologue of 12-HETE when the source is AA. Fish oil supplementation has been used as a preventive measure against a number of diseases including coronary heart disease, cancer, and inflammatory bowel disease (IBD). IBD and other intestinal diseases are associated with the disruption of epithelial barrier function( 1 ). In this sense, we recently demonstrated that PGE2, which is increased in the mucosa of IBD patients, induces the disruption of this barrier in differentiated Caco-2 cells( 2 ). In this line, the present study aims to investigate the potential of 12-LOX derived eicosanoids 12-HETE and ...
Welcome to the Eicosanoid Core Laboratory! Eicosanoid is an umbrella term used to describe any oxidized derivative of arachidonic acid, a ubiquitous polyunsaturated fatty acid (PUFA) in humans. Arachidonic acid can be oxidized in vivo via both enzymatic and non-enzymatic mechanisms to yield bioactive lipid mediators that are of central importance to human physiology and pathophysiology. The Eicosanoid Core Laboratory at Vanderbilt University was established in 1988 in order to provide investigators at the university with a central location for the analysis of oxidized fatty acids and their metabolites including isoprostanes, prostaglandins, leukotrienes, hydroxy-PUFAs (HETEs), and epoxy-PUFAs (EETs). Today the Eicosanoid Core Laboratory serves investigators not only at Vanderbilt but indeed around the world. Click here for available assays. The Eicosanoid Core Lab provides services in three general areas: Isoprostanes Prostaglandins Leukotrienes Here you can find the Eicosanoid Cores Shipping
Welcome to the Eicosanoid Core Laboratory! Eicosanoid is an umbrella term used to describe any oxidized derivative of arachidonic acid, a ubiquitous polyunsaturated fatty acid (PUFA) in humans. Arachidonic acid can be oxidized in vivo via both enzymatic and non-enzymatic mechanisms to yield bioactive lipid mediators that are of central importance to human physiology and pathophysiology. The Eicosanoid Core Laboratory at Vanderbilt University was established in 1988 in order to provide investigators at the university with a central location for the analysis of oxidized fatty acids and their metabolites including isoprostanes, prostaglandins, leukotrienes, hydroxy-PUFAs (HETEs), and epoxy-PUFAs (EETs). Today the Eicosanoid Core Laboratory serves investigators not only at Vanderbilt but indeed around the world. Click here for available assays. The Eicosanoid Core Lab provides services in three general areas: Isoprostanes Prostaglandins Leukotrienes Here you can find the Eicosanoid Cores Shipping
TG(18:0/20:4(5Z,8Z,11Z,14Z)/20:4(5Z,8Z,11Z,14Z))[iso3] is a diarachidonic acid triglyceride. Triglycerides (TGs) are also known as triacylglycerols or triacylglycerides, meaning that they are glycerides in which the glycerol is esterified with three fatty acid groups (i.e. fatty acid tri-esters of glycerol). TGs may be divided into three general types with respect to their acyl substituents. They are simple or monoacid if they contain only one type of fatty acid, diacid if they contain two types of fatty acids and triacid if three different acyl groups. Chain lengths of the fatty acids in naturally occurring triglycerides can be of varying lengths and saturations but 16, 18 and 20 carbons are the most common. TG(18:0/20:4(5Z,8Z,11Z,14Z)/20:4(5Z,8Z,11Z,14Z))[iso3], in particular, consists of one chain of stearic acid at the C-1 position, one chain of arachidonic acid at the C-2 position and one chain of arachidonic acid at the C-3 position. TGs are the main constituent of vegetable oil and animal ...
There has been a considerable increase in our understanding of the role of arachidonic acid metabolites in asthma over the last decade. Arachidonic acid provides a source for both leukotrienes and prostanoids which have a diverse range of properties that are important in regulating the airway inflammatory response. It is clear that cysteinyl leukotrienes are important pro-inflammatory mediators in asthma which act to enhance bronchoconstriction. This has led to the development of a number of agents which either target the enzymes involved in leukotriene synthesis or are antagonists at specific leukotriene receptors. The development of these agents has allowed the role of leukotrienes in different variants of asthma to be studied. The other arm of arachidonic acid metabolism is the cyclo-oxygenase pathway. Cyclo-oxygenase exists in two forms-a constitutive form, COX-1, responsible for the production of housekeeping prostaglandins, and an inducible form, COX-2, which is involved in inflammatory ...
Genes Encoding Enzymatic Activities Implicated in the Eicosanoid Cascade of Arachidonic Acid and their Receptors are Expressed at mRNA Levels in Human Meningiomas Abstract.
Introduction:. Excessive menstrual bleeding, or menorrhagia, is a common female complaint that may be entirely prevented by a simple herbal prescription - capsules of ginger. The chief cause of functional menorrhagia (i.e., not caused by the presence of uterine fibroids or endometriosis) involves abnormalities in the biochemical processes of the endometrium (the lining of the uterus).. One abnormality commonly found is an alteration in arachidonic acid metabolism. This fatty acid is derived from meat and dairy sources and is converted to hormone-like compounds known as prostaglandins. The endometrium of women who have menorrhagia concentrates arachidonic acid to a much greater extent than normal. The increased arachidonic acid release during menstruation results in increased production of prostaglandin E2 (PGE2), which not only leads to excessive bleeding, but also menstrual cramps.. Background Data:. Historically, the majority of complaints for which ginger (Zingiber officinale) was used ...
Prostaglandins - biologically active substances produced in cells from arachidonic and some other unsaturated fatty acids (thomayerova) contained in the phospholipids of membranes. Depending on the pathways of enzymatic biotransformation arachidonic acid can be formed not only GHG (including prostacyclin and thromboxane of the corresponding synthase), and leukotrienes (products of oxidation of 5-lipooksigenaznomu mechanism).. The peculiarities of the chemical structure of PG is divided into groups, with Latin indices A, b, E, F, etc., and subgroup, denoted by Arabic numerals (PGE1, PGE2, etc.), according to the number of double bonds in the molecule ...
Introduction. 15-lipoxygenase-2 (15-LOX-2) is a lipid oxidizing enzyme which converts the unsaturated fatty acids (Arachidonic and linoleic acid) to bioactive lipids with anti-inflammatory properties. Abundantly expressed in normal prostate, 15-LOX-2 expression and activities were found reduced in prostate tumors. 15-LOX-2 has been suggested as functional tumor suppressor since restoration of its expression was found to reduce prostate tumor formation and growth and induce tumor dormancy. However, it is unknown how 15-LOX-2 modulates prostate tumor progression and metastasis.. Methods. Silico analyses of gene array data, Inducible Tet-on system to express 15-LOX-2 in PC3MM cells in an inducible manner, qPCR to check the expressions, western blot, wound healing assay, immunohistochemistry.. Result. Through in silico analyses of gene array data, we found 15-LOX-2 expression was markedly reduced in metastatic prostate tumors when compared to normal or primary prostate tumor tissues. To determine ...
Deregulation of the oxidative cascade of poly-unsaturated fatty acids (PUFAs) has been associated with several cancers, including chronic lymphocytic leukemia (B-CLL). Leukotriene B4 (LTB4), a metabolite of arachidonic acid (AA), is produced by B-CLL and contributes to their survival. The aim of the present study was to analyze the activity of the oxidative cascade of PUFAs in B-CLL. Purified B cells from patients and normal B CD5 positive cells were subjected to flow cytometry, Western-blot and RT-qPCR analyses. LTB4 plasma and intracellular concentrations were determined by ELISA. Our results showed that aggressive B-CLL tumor cells, i.e. cells with an annual proliferation index above 2, over-expressed calcium-dependent and calcium-independent phospholipases A2 (cPLA2-alpha and iPLA2-beta, respectively), 5-lipoxygenase (5LOX) and leukotriene A4 hydroxylase (LTA4H). Intracellular LTB4 levels were lower in the most aggressive cells than in cells with a smaller proliferation index, despite equivalent
The hospitalization rate for acute coronary syndrome (ACS) for people aged ≤50 has remained stable over the past decade. Increased serum levels of n-3 polyunsaturated fatty acids (PUFAs), such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are associated with a decreased incidence of cardiovascular events and mortality in older patients; however, it is currently unknown whether reduced serum levels of n-3 PUFAs is also a risk factor for ACS in patients aged ≤50 years. We retrospectively reviewed 102 (male/ female 73/29) Japanese ACS patients whose serum levels of EPA/arachidonic acid (AA) and DHA/AA were evaluated on admission. The EPA/AA ratio was the lowest in patients aged ≤50 compared to patients aged 51-74 and ≥75. Pearson correlation analysis showed that early ACS onset was associated with low EPA/AA and DHA/AA ratios, and multiple regression analysis determined that decreased ratios of EPA/AA and DHA/AA, and male sex, current smoker status, increased body mass index and
2Endogenous membrane bound phospholipase A2 was measured with labelled phospholipids used as substrates. The enzyme activity with phosphatidylcholine and phosphatidylethanolamine as substrates was inhibited by 27.0 ± 8.3% and 23.3 ± 11.1% (n = 4) respectively, in dexamethasone-treated macrophages compared to control cells. Neither the distribution of radiolabelled arachidonic acid among the different phospholipid species nor the release of arachidonic acid from prelabelled cells were significantly impaired by pretreatment of the macrophages with dexamethasone (1 μm ...
Chemicals. Retinol, retinal, retinoic acid, and arachidonic acid were purchased from Sigma-Aldrich (St. Louis. MO). 14C-labeled substrates were purchased from PerkinElmer Life and Analytical Sciences (Boston, MA), and 3H-DMBA was obtained from Amersham Biosciences Inc. (Piscataway, NJ). Complete Protease Inhibitor Tablets were obtained from Roche Diagnostics (Indianapolis, IN). The QuikChange Site-Directed Mutagenesis Kit was obtained from Stratagene (La Jolla, CA). Human CYP1A1 and CYP1B1 Supersomes were obtained from BD Gentest (Woburn, MA). Arachidonate metabolite standards 20-HETE, 15-HETE, 11-HETE, 9-HETE, 5-HETE, 8-HETE, and 12-HETE; and 14,15-EET, 11,12-EET, 8,9-EET, and 5,6-EET were obtained from Cayman Chemical (Ann Arbor, MI).. Expression and Purification of CYP1B1 and Cyp1b1. Human CYP1B1 was expressed and purified as described earlier (Jansson et al., 2001). The mouse Cyp1b1 transcript was prepared from a cDNA library using primers with modification at the 5′ end containing the ...
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While reading up on vitamin K2 recently, Ive noticed a number of connections that have me wondering if one of the culprits behind several widely occurring neurological diseases might be a relative scarcity of this vitamin in many peoples diets. … Continue reading →. ...
O. Arditti. - "Un nouvel algorithme de recherche dun ordre induit par des comparaisons par paires", in Data Analysis and Informatics III, E. Diday et autres edit., North-Holland, 1984 (323-343). , Zbl 0565.90030 M. Barbut. - Médianes, Condorcet et Kendall, Note SEMA, Paris, 1967, et Math. Sci. hum. 69 (1980) 5-13. , Numdam , MR 571612 , Zbl 0437.90010 M. Barbut et B. Monjardet. - Ordre et classification, Algèbre et Combinatoire, 2 tomes, Hachette, Paris, 1970. , Zbl 0267.06001 J.P. Barthelemy. - "Caractérisations axiomatiques de la distance de la différence symétrique entre des relations binaires", Math. Sci. Hum. 67 (1979) 85 -114. , Numdam , Zbl 0418.06003 J.P. Barthelemy, C1. FLAMENT et B. Monjardet. - "Ordered sets and social sciences", in Ordered sets, I. Rival edit., D. Reidel, 1982 (721-758). , MR 661311 , Zbl 0493.90005 J.P. Barthelemy et B. Monjardet. - "The median procedure in cluster analysis and social choice theory", Math. Soc. Sci., 1, 3 (1981) 235-267. , MR 616379 , Zbl ...
The major metabolite in neutrophil polymorphonuclear leukocytes. It stimulates polymorphonuclear cell function (degranulation, formation of oxygen-centered free radicals, arachidonic acid release, and metabolism). (From Dictionary of Prostaglandins and Related Compounds, 1990 ...
AACOCF₃ - CAS 149301-79-1 - Calbiochem CAS 149301-79-1 A cell-permeable trifluoromethyl ketone analog of arachidonic acid. - Find MSDS or SDS, a COA, data sheets and more information.
Eicosanoids are metabolites of Arachidonic acid which is a fatty acid component of phospholipids in plasma membrane of almost all cells. They primarily play a critical role in cardiovascular, inflammatory and reproductive physiology.
In this study the, in vitro, influence of arachidonic acid metabolites on human β-adrenoceptors was investigated. Incubation of normal human pulmonary membranes with PAF, LTB4 and LTC4 affected...
A 1 g oral dose of AA can raise plasma AA to 130 µmol/L within an hour and such doses at intervals of about two hours throughout the day can maintain ~230 µmol AA/L.5 Similar levels could also be achieved by use of sustained-release AA tablets. This AA concentration would induce an approximate 0.7 depression in GHb. The GHb assay used in our study, affinity chromatography, is not affected by the presence of AA.3 Thus, unlike the case with Hb D Punjab, our results were not caused by analytical method artifact. More likely, the decreased GHb associated with AA supplementation appears related to an in vivo inhibition of glycation by the elevated plasma AA levels, and not a decrease in average plasma glucose.3 If this is true, the effect has implications not only for interpretation of GHb but also for human ageing, in which glycation of proteins plays a prominent role in age-related degenerative changes ...
ethyl arachidonate 1808-26-0 NMR spectrum, ethyl arachidonate H-NMR spectral analysis, ethyl arachidonate C-NMR spectral analysis ect.
The chemical reactions and pathways involving leukotriene, a pharmacologically active substance derived from a polyunsaturated fatty acid, such as arachidonic acid.
A prostaglandin is one of several hormone-like substances that participate in a wide range of body functions. For example, its involved in contracting and relaxing smooth muscle; dilating and constricting blood vessels; control of blood pressure; and modulation of inflammation. Prostaglandins are derived from a chemical called arachidonic acid.. ...
LTC4, LTD4, and LTE4 are leukotrienes (cys-LTs) derived from arachidonic acid as a result of immune or inflammatory stimuli. The above mentioned…
Hill, D J. and Borysenko, J Z., "Restriction of patching of bound concanavalin a after incorporation of arachidonic acid into the plasma membrane of virally transformed fibroblasts." (1979). Subject Strain Bibliography 1979. 3532 ...
COMMON DYSREGULATION AMONG ALLERGIC CONDITIONS. Allergic asthma, allergic rhinitis and atopic dermatitis are prevalent allergic diseases. These diseases can be distinguished by the location of their most important symptoms; lungs, sinuses and skin respectively.. They also share many characteristics, including the same underlying immune system dysregulation as evidenced by inappropriate T-cell mediated responses to innocuous antigens, peripheral eosinophilia, elevated serum IgE levels, chronic immune system activation, and over-production of inflammatory mediators, including leukotrienes, cytokines and chemokines.. LEUKOTRIENES AND INFLAMMATION IN ALLERGIC DISEASES. Leukotrienes are eicosanoid lipid mediators and are derived from the essential fatty acid arachidonic acid (AA), which is concentrated in the membrane phospholipids of cells of the immune system. The role of inflammatory mediators (leukotrienes) in allergic diseases is well characterized. In particular, leukotrienes play a significant ...
TY - JOUR. T1 - Arachidonic acid increases intracellular calcium in erythrocytes. AU - Soldati, Laura. AU - Lombardi, Cinzia. AU - Adamo, Donatella. AU - Terranegra, Annalisa. AU - Bianchin, Cristiana. AU - Bianchi, Giuseppe. AU - Vezzoli, Giuseppe. PY - 2002. Y1 - 2002. N2 - Recently, we have measured in erythrocytes a voltage-modulated and dihydropyridine-inhibited calcium influx. Since arachidonic acid and other polyunsaturated fatty acids influence the activities of most ion channels, we studied their effects on the erythrocyte Ca2+ influx. It was measured on fresh erythrocytes, isolated from healthy donors, using the fluorescent dye Fura 2 as indicator of [Ca2+]i. AA (5-50 μM) and EPA (20-30 μM) stimulated a concentration-dependent increase in [Ca2+]i, deriving from extracellular calcium (1 mM), without affecting the intra- and extracellular pH and membrane voltage. The Ca2+ influx rate varied from 0.5 to 3 nM Ca2+/s in the presence of AA and from 0.9 to 1.7 nM Ca2+/s with EPA. The Ca2+ ...
TY - JOUR. T1 - Platelet membrane glycoprotein IV (CD36) is involved in arachidonic acid induced-platelet aggregation. AU - Dutta-Roy, Asim K. AU - Crosbie, Lynn. AU - Gordon, Margaret Jane. AU - Campbell, Fiona Margaret. PY - 1996/5/1. Y1 - 1996/5/1. KW - Antibodies, Monoclonal. KW - Antigens, CD. KW - Antigens, CD36. KW - Arachidonic Acid. KW - Blood Platelets. KW - Humans. KW - Platelet Aggregation. M3 - Article. C2 - 8736825. VL - 24. SP - 167S. JO - Biochemical Society Transactions. JF - Biochemical Society Transactions. SN - 0300-5127. IS - 2. ER - ...
Antibodies for proteins involved in arachidonic acid epoxygenase activity pathways, according to their Panther/Gene Ontology Classification
Neuroinflammation plays a vital role in Alzheimers disease and other neurodegenerative conditions. Microglia are the resident mononuclear immune cells of the central nervous system, and they play essential roles in the maintenance of homeostasis and responses to neuroinflammation. The orphan G-protein-coupled receptor 55 (GPR55) has been reported to modulate inflammation and is expressed in immune cells such as monocytes and microglia. However, its effects on neuroinflammation, mainly on the production of members of the arachidonic acid pathway in activated microglia, have not been elucidated in detail. In this present study, a series of coumarin derivatives, that exhibit GPR55 antagonism properties, were designed. The effects of these compounds on members of the arachidonic acid cascade were studied in lipopolysaccharide (LPS)-treated primary rat microglia using Western blot, qPCR, and ELISA. We demonstrate here that the various compounds with GPR55 antagonistic activities significantly inhibited the
FungiEicosanoids were first discovered in fungi in the early 1990s through investigation of fungal fatty acid production in environmental fungi (64). Since that time, eicosanoid and oxylipin production has been observed in a number of fungal species. A survey of both pathogenic and nonpathogenic fungal species reveals that all species produce detectable amounts of both cyclooxygenase and lipoxygenase products endogenously and from arachidonic acid (97). Investigations of fungal eicosanoid products and their pathways indicate a role in sexual maturation and life cycle control as well as in pathogenesis of virulent fungi.. The arachidonic acid metabolites PGF2α and PGF2α-lactone have been detected in a number of environmental yeasts of the Lipomycetaceae family (Dipodascopsis, Lipomyces, Zygozyma, and Myxozyma), as well as Saccharomyces cerevisiae (64). Fungal extracts inhibit blood platelet aggregation, a well-known function of PGF2α, and the production of these compounds can be inhibited by ...
Arachidonic acid[edit]. ALOX5 metabolizes the omega-6 fatty acid, Arachidonic acid (AA, i.e. 5Z,8Z,11Z,15Z-eicosatrienoic acid ... Eicosapentaenoic acid[edit]. ALOX5 metabolizes the omega-3 fatty acid, Eicosapentaenoic acid (EPA, i.e. 4Z,8Z,11Z,14Z,17Z- ... Mead acid[edit]. Mead acid (i.e. 5Z,8Z,11Z-eicosatrienoic acid) is identical to AA except that has a single rather than double ... Docosahexaenoic acid[edit]. ALOX5 acts in series with ALOX15 to metabolize the omega 3 fatty acid, docosahexaenoic acid (DHA, i ...
General: Arachidonic acid. *DAG (PKC, TRPC). *IP3 (IP3R, RyR) ... Vedaprofen; Anthranilic acids (fenamic acids): Etofenamic acid ... Since diacylglycerol is synthesized via phosphatidic acid, it will usually contain a saturated fatty acid at the C-1 position ... or free fatty acids.(See Dietary sources of fatty acids, their digestion, absorption, transport in the blood and storage for ... to form lysophosphatidic acid, which is then acylated with another molecule of acyl-CoA to yield phosphatidic acid. ...
... -A synthase, an enzyme found in platelets, converts the arachidonic acid derivative prostaglandin H2 to thromboxane ... Omega-3 fatty acids are metabolized to produce higher levels of TxA,3 which is relatively less potent than TxA2 and PGI3; ... Tiaprofenic acid (tiaprofenate). *Vedaprofen; Anthranilic acids (fenamic acids): Etofenamic acid (etofenamate). *Floctafenic ...
These convert arachidonic acid to prostaglandin H2 (PGH2), the immediate precursor of prostacyclin. Since thromboxane (an ... PGI2 is derived from the ω-6 arachidonic acid. PGI3 is derived from the ω-3 EPA. ... Z)-5-[(4R,5R)-5-Hydroxy-4-((S,E)-3-hydroxyoct-1-enyl)hexahydro-2H-cyclopenta[b]furan-2-ylidene]pentanoic acid ... Fischer S, Weber PC (1985). "Thromboxane (TX)A3 and prostaglandin (PG)I3 are formed in man after dietary eicosapentaenoic acid ...
Increased arachidonic acid turnover[23]. *Increased cytokine synthesis[26]. Imaging studies have shown that the left amygdala ...
This enzyme participates in arachidonic acid metabolism. Catalyzed reaction[edit]. The chemical reaction catalyzed by LTA4H. ... Enzymatic conversion into 5,6-dihydroxy-7,9,11,14-eicosatetraenoic acid by mouse liver cytosolic epoxide hydrolase". J. Biol. ... "Molecular cloning and amino acid sequence of leukotriene A4 hydrolase". Proc. Natl. Acad. Sci. U.S.A. 84 (19): 6677-81. doi ...
Eicosanoids act as neuromodulators via the Arachidonic acid cascade. Orexins (-A and -B) are involved in a number of cognitive ... "Arachidonic Acid". Neuropsychopharmacology: The Fifth Generation of Progress. Retrieved 2006-03-03. "Neurotrophic factors". ...
Capric acid,[1] n-Capric acid, n-Decanoic acid, Decylic acid, n-Decylic acid, C10:0 (Lipid numbers) ... Decanoic acid (capric acid, C10:0) is a saturated fatty acid. Its formula is CH3(CH2)8COOH. Salts and esters of decanoic acid ... Two other acids are named after goats: caproic (a C6:0 fatty acid) and caprylic (a C8:0 fatty acid). Along with decanoic acid, ... Nonanoic acid, a medium-chain fatty acid, also with antiseizure activity. References[edit]. *^ a b c d n-Decanoic acid in ...
... is the first fatty acid produced during fatty acid synthesis and is the precursor to longer fatty acids. As a ... Palmitic acid, or hexadecanoic acid in IUPAC nomenclature, is the most common saturated fatty acid found in animals, plants and ... Palmitic acid strongly boosts metastasis in mouse models of human oral cancer cells. Among all fatty acids, it has the ... Aluminium salts of palmitic acid and naphthenic acid were combined during World War II to produce napalm. The word "napalm" is ...
Arachidonic acid (AA), i.e. 5Z, 8Z,11Z,14Z-eicosatetraenoic acid is ω-6 fatty acid, with four double bonds in the cis ... all of which are less active than there arachidonic acid analogs. Since eicosapentaenoic acid competes with arachidonic acid ... Arachidonic acid (AA; 20:4 ω-6) sits at the head of the "arachidonic acid cascade" - more than twenty eicosanoid-mediated ... arachidonic acid viz., 5,6-epoxy-eicsattrienoic acid (5,6-EET), 8,9-EET, 11,12-EET, and 14,15-EET (see Epoxyeicosatrienoic acid ...
First, Phospholipase A2 (PLA2) facilitates the conversion of phospholipids to Arachidonic Acid, the framework from which all ... The Arachidonic Acid then reacts with two Cyclooxygenase (COX) receptors, COX-1 and COX-2 to form Prostaglandin H2, an ... Z)-7-[(1R,2R,3R,5S)-3,5-dihydroxy-2-[(E,3S)- 3-hydroxyoct-1-enyl]cyclopentyl]hept-5-enoic acid ... Tiaprofenic acid (tiaprofenate). *Vedaprofen; Anthranilic acids (fenamic acids): Etofenamic acid (etofenamate). *Floctafenic ...
γ-Linolenic acid (gamolenic acid). *Dihomo-γ-linolenic acid. *Diacylglycerol. *Arachidonic acid ... Tafluprost acid is inactivated by beta oxidation to 1,2-dinortafluprost acid, 1,2,3,4-tetranortafluprost acid, and its lactone ... Tafluprost, as a lipophilic ester, easily penetrates the cornea and is then activated to the carboxylic acid, tafluprost acid. ... From left to right: tafluprost, tafluprost acid (the active metabolite), 1,2-dinortafluprost acid, 1,2,3,4-tetranortafluprost ...
... works by preventing the synthesis of another omega metabolite known as arachidonic acid. Arachidonic acid is an omega 6, making ... Lee, Je Min; Lee, Hyungjae; Kang, SeokBeom; Park, Woo Jung (2016-01-04). "Fatty Acid Desaturases, Polyunsaturated Fatty Acid ... Omega 3 fatty acids are increasingly being used to treat pruritic, irritated skin. A group of dogs supplemented with omega 3 ... Marsh, K.a.; Ruedisueli, F.l.; Coe, S.l.; Watson, T.g.d. (2000-12-01). "Effects of zinc and linoleic acid supplementation on ...
Piomelli, Daniele (2000). „Arachidonic Acid". Neuropsychopharmacology: The Fifth Generation of Progress. Приступљено 3. 3. 2006 ... Fatty Acids. 61 (1): 55-64. PMID 10477044. doi:10.1054/plef.1999.0074.. ,access-date=. захтева ,url=. (помоћ) ... DeCaterina, R & Basta, G (2001). „n-3 Fatty acids and the inflammatory response - biological background" (PDF). European Heart ... Nutrigenomic approach to understanding the mechanisms by which dietary long-chain fatty acids induce gene signals and control ...
These enzymes epoxidize the double bonds in arachidonic acid to form four regioisomers. Arachidonic acid is also the precursor ... There are epoxides of other lipids besides arachidonic acid such as the omega three docosahexaenoic acid (DHA) and ... Moghaddam M, Motoba K, Borhan B, Pinot F, Hammock BD (August 1996). "Novel metabolic pathways for linoleic and arachidonic acid ... Spector AA (April 2009). "Arachidonic acid cytochrome P450 epoxygenase pathway". J. Lipid Res. 50 Suppl (Suppl): S52-6. doi: ...
... to the n-6 highly unsaturated fatty acid (n-6HUFA), arachidonic acid (20:4n-6), competitively displaces n-3 HUFA from tissue ... 2015 Alan Brash from Vanderbilt University on arachidonic acid metabolites and their role in pathophysiological processes ... "Omega-3 PUFAs lower the propensity for arachidonic acid cascade over-reactions". BioMed Res Int. 2015: 555. doi:10.1155/2015/ ... "Prostaglandins Leukot Essent Fatty Acids. 99: 19-23. doi:10.1016/j.plefa.2015.04.005. PMID 26002802.. ...
Mortierella alpina Strain: ATCC 32222, commercial source of arachidonic acid (2011[119]) ...
This enzyme participates in arachidonic acid metabolism. As of late 2007[update], 7 structures have been solved for this class ...
This enzyme participates in arachidonic acid metabolism. As of late 2007, 3 structures have been solved for this class of ...
This enzyme participates in arachidonic acid metabolism. Watanabe K, Shimizu T, Iguchi S, Wakatsuka H, Hayashi M, Hayaishi O ( ...
This enzyme participates in arachidonic acid metabolism. Orning L (1987). "Omega-oxidation of cysteine-containing leukotrienes ...
This enzyme participates in arachidonic acid metabolism. As of late 2007, 3 structures have been solved for this class of ...
Regulation of arachidonic acid metabolites in macrophages. J. Exp. Med. 152:324-335. 1982 With W. A. Scott, N. A. Pawlowski, H ... Regulation of arachidonic acid metabolism by macrophage activation. J. Exp. Med. 155:1148-1160. With W. C. Van Voorhis, G. ... Bacterial lipopolysaccharides prime macrophages for enhanced release of arachidonic acid metabolites. J. Exp. Med. 164:165-179 ...
This enzyme participates in arachidonic acid metabolism. It employs one cofactor, heme. Romano MC, Eckardt RD, Bender PE, ...
This enzyme participates in arachidonic acid metabolism. Sok DE, Kang JB, Shin HD (1988). "15-Hydroxyeicosatetraenoic acid ... H+ The 3 substrates of this enzyme are 15-Hydroxyicosatetraenoic acid (i.e. 15(S)-15-hydroxy-5,8,11-cis-13-trans- ...
... which catalyzes the conversion of arachidonic acid to leukotriene B4 (LTB4).[45] LTB4 promotes skin inflammation by acting on ... Salicylic acid[edit]. Salicylic acid is a topically applied beta-hydroxy acid that stops bacteria from reproducing and has ... "Topical azelaic acid, salicylic acid, nicotinamide, sulphur, zinc and fruit acid (alpha-hydroxy acid) for acne". Cochrane ... lactic acid, salicylic acid, Jessner's solution, or a lower concentration (20%) of trichloroacetic acid. These peels only ...
Arachidonic acid (AA) is a 20-carbon ω-6 conditionally essential fatty acid. It sits at the head of the "arachidonic acid ... In the arachidonic acid cascade, dietary linoleic acid (18:2 ω-6) is desaturated and lengthened to form arachidonic acid, ... Daniele Piomelli Arachidonic Acid The arachidonic acid cascade proceeds somewhat differently in the brain. Neurohormones, ... IV Supplementation with gamma-linolenic acid increased serum GLA but did not increase the plasma percentage of arachidonic acid ...
Health effects of arachidonic acid supplementation[edit]. Arachidonic acid supplementation in daily doses of 1,000-1,500 mg for ... Arachidonic acid is not one of the essential fatty acids. However, it does become essential if a deficiency in linoleic acid ... Arachidonic acid is also used in the biosynthesis of anandamide.[17]. *Some arachidonic acid is converted into ... Dietary arachidonic acid and inflammation[edit]. Increased consumption of arachidonic acid will not cause inflammation during ...
A polyunsaturated fatty acid, CH3(CH2)3(CH2CH:CH)4(CH2)3COOH, that is essential for growth in mammals (see eicosanoid [1]). It ... arachidonic acid A long chain polyunsaturated fatty acid (20 : 4 ω6). Not strictly an essential fatty acid, since it can be ... arachidonic acid A polyunsaturated fatty acid, CH3(CH2)3(CH2CH:CH)4(CH2)3COOH, that is essential for growth in mammals (see ... arachidonic acid (ă-rak-i-don-ik) n. see essential fatty acid. ... "arachidonic acid." A Dictionary of Biology. . Encyclopedia.com. ...
I spend a lot of time highlighting the importance of omega-3 fatty acids and downplaying their poly cohorts, omega-6s. Of ... If youre getting plenty of linoleic acid in your diet, your body can make arachidonic acid. First, linoleic acid, abundant in ... Actually, arachidonic acid may have little to do with ones intake of linoleic acid. All the same then, it probably isnt the ... Arachidonic acid is both a product of the bodys natural linoleic acid conversion and, as the question notes, an existing (but ...
... releases arachidonic acid. ANSWER QUESTION: What enyzme acts on arachidonic acid and begins the process through which ... Derivatives of an n-6 Polyunsaturated Fatty Acid. An important family of regulatory molecules is derived from arachidonic acid ... QUESTION: What molecule is the source of arachidonic acid and where is it found? ANSWER QUESTION: Name the enzyme that, when ... Derivatives of n-3 Polyunsaturated Fatty Acids. The above introduces regulatory molecules derived from arachidonic acid. These ...
Arachidonic Acid News and Research. RSS Arachidonic acid is an omega-6 fatty acid that is present in the phospholipids ( ... Fatty acids may be the culprit in Alzheimers According to new research from the U.S. controlling the level of a fatty acid in ... Fatty acids such as those found in corn oil turn on genes that stimulate tumor growth Omega-6 fatty acids--such as those found ... Altering fatty acid levels in diet may reduce prostate cancer growth rate UCLA researchers found that altering the fatty acid ...
Arachidonic acid 5-hydroperoxide (5-hydroperoxyeicosatetraenoic acid, 5-HPETE) is an intermediate in the metabolism of ... 5-Hydroxyicosatetraenoic acid and 5-oxo-eicosatetraenoic acid; or c) the specialized pro-resolving mediators of inflammation, ... arachidonic acid by the ALOX5 enzyme in humans or Alox5 enzyme in other mammals. The intermediate is then further metabolized ...
Arachidonic acid is also used in the biosynthesis of anandamide.[17]. *Some arachidonic acid is converted into ... Health effects of arachidonic acid supplementationEdit. Arachidonic acid supplementation in daily dosages of 1,000-1,500 mg for ... Dietary arachidonic acid and inflammationEdit. Increased consumption of arachidonic acid will not cause inflammation during ... and phosphatidic acid. BrainEdit. Arachidonic acid is one of the most abundant fatty acids in the brain, and is present in ...
... polyunsaturated fatty acid or n-6 PUFA. It is made in the body from shorter omega-6 fatty acids found in vegetable oils, or ... Arachidonic acid, AA and sometimes ARA, is a 20 carbon long, omega-6, ... Arachidonic acid, AA and sometimes ARA, is a 20 carbon long, omega-6, polyunsaturated fatty acid or n-6 PUFA. It is made in the ... The Journal of the International Society of Sports Nutrition: Effects Of Arachidonic Acid Supplementation On Training ...
These are saturated fats, trans fats and (AA) arachidonic acid. I consider these to be really bad fats. Arachidonic acids are ... arachidonic acid into the same rabbits they are dead within three minutes. The human body needs some arachidonic acid, but ... Understanding (AA) Arachidonic Acid - (Omega 6 - Pro Inflammatory Fat). Dr. Barry Sears. Zone Living. CBN.com There are two ... is stimulated to make increased levels of arachidonic acid. (AA) is a long-chain omega-6 fatty acid. Enchaned production of ...
Hanna, V. S., Gawish, A., Abou El-Dahab, M., Tallima, H., & El Ridi, R. (2018). Is arachidonic acid an endoschistosomicide? ... mansoni infection might be ascribed to stores of arachidonic acid (ARA)-rich lipids in liver. Several reports have previously ...
T 2370/09 (Arachidonic acid/MARTEK) of 26.5.2014. European Case Law Identifier:. ECLI:EP:BA:2014:T237009.20140526. ...
Get to know arachidonic acid and experience gains like the old days! ... Arachidonic acid isnt considered an essential fatty acid, because your body can synthesize it from linoleic acid in the liver ... Rett, B., & Whelan, J. (2011). Increasing Dietary Linoleic Acid Does Not Increase Tissue Arachidonic Acid Content in Adults ... WHAT IS ARACHIDONIC ACID?. Basically, ARA is the primary fatty acid responsible for inflammation in muscle tissue. This 20- ...
... acid, were also indetectable in these lipids. On the basis of these results, it appears that the arachidonic acid cascade is ... Evidence that arachidonic acid is deficient in phosphatidylinositol of Drosophila heads.. Yoshioka T, Inoue H, Kasama T, Seyama ... Since arachidonic acid is considered to be a key molecule in phosphatidylinositol turnover in the brain, it is of interest that ... We have found that arachidonic (20 : 4) acid is indetectable in phosphatidylinositol and diacyglycerol extracted from ...
Naturally occurring, weight training can reduce levels creating a need for supplemental Arachidonic Acid. ... Arachidonic Acid is an Omega-6 fatty acid essential for muscle hypotrophy. ... Arachidonic Acid Chemical Composition. (5Z,8Z,11Z,14Z)-icosa-5,8,11,14-tetraenoic acid. Formula: C20 H32 O2 ... Arachidonic acid (AA) is a naturally occurring omega-6 essential fatty acid. Its the principle building block for the synthesis ...
Arachidonic acid (ARA) is one of the two main polyunsaturated fatty acids (PUFAs) in the brain, especially in neuronal cells, ... Arachidonic Acid: Sources, Biosynthesis and Health Effects. Jason M. OKeefe (Editor). Series: Biochemistry Research Trends. ... Home / Shop / Books / Science and Technology / Chemistry / Arachidonic Acid: Sources, Biosynthesis and Health Effects. ... Chapter 4 - Arachidonic Acid, Cyclooxygenase and Hepatic Inflammation (pp. 127-134). Sura Wanessa Santos Rocha and Christina ...
Arachidonic acid and acetylcholine had no effect on denuded rabbit aorta. Incubation of rabbit aorta with [14C]arachidonic acid ... and the effect of various agents on arachidonic acid- and acetylcholine-induced relaxations was examined. Arachidonic acid ... had little or no effect on arachidonic acid-induced relaxations. In contrast, nordihydroguaiaretic acid, metyrapone, NG- ... Arachidonic acid- and acetylcholine-induced relaxations of rabbit aorta.. S L Pfister, W B Campbell ...
K. Yang, W. Ma, H. Liang, Q. Ouyang, C. Tang, and L. Lai, "Dynamic simulations on the arachidonic acid metabolic network," PLoS ... S. H. Hong, I. Avis, M. D. Vos, A. Martínez, A. M. Treston, and J. L. Mulshine, "Relationship of arachidonic acid metabolizing ... Y. Cao, A. T. Pearman, G. A. Zimmerman, T. M. McIntyre, and S. M. Prescott, "Intracellular unesterified arachidonic acid ... In devising therapeutic strategies, with the arachidonic acid products, greater attention to the impact of levels of mediators ...
Evidence that proline-directed phosphorylation is not required for mobilization of arachidonic acid by cPLA," Journal of ... M. A. Balboa, J. Balsinde, and E. A. Dennis, "Involvement of phosphatidase phosphohydrolase in arachidonic acid mobilization in ... LysoPC and PAF Trigger Arachidonic Acid Release by Divergent Signaling Mechanisms in Monocytes. ... "Phosphorylation of cytosolic phospholipase A and the release of arachidonic acid in human neutrophils," Journal of Immunology, ...
Arachidonic acid is found in animal products, like poultry and eggs. The amount of arachidonic acid found in just one egg a day ... Arachidonic Acid and Mental Health. Arachidonic acid may trigger brain inflammation. High blood levels have been associated ... Inflammatory Remarks about Arachidonic Acid. Arachidonic acid may play a role in cancer, asthma, inflammatory bowel disease, ... Arachidonic acid is an inflammatory omega-6 fatty acid. Our bodies produce this nutrient, and its excess may lead to ...
Arachidonic Acid in Cell Signaling has 2 available editions to buy at Alibris ... Arachidonic Acid in Cell Signaling by Daniele Piomelli starting at $61.69. ... Arachidonic acid may serve as an intracellular second messenger in many cell types, as well as precursor for biologically ... Arachidonic acid may serve as an intracellular second messenger in many cell types, as well as precursor for biologically ...
Arachidonic acid may play a role in cancer, asthma, inflammatory bowel disease, rheumatoid arthritis, and other autoimmune ... Arachidonic acid is produced in the body from linoleic acid (LA) by three enzymes. More arachidonic acid is made if the ratio ... Is there enough arachidonic acid & palmitic acid in peanuts to justify limiting their consumption? ... This, coupled with a diet rich in vegetable oils, means the mutated gene turns fatty acids into arachidonic acid. ...
Crystall Swarbrick, Noelia Roman and Jade K. Forwood (December 16th 2011). Role of ACOT7 in Arachidonic Acid Production and ... Crystall Swarbrick, Noelia Roman and Jade K. Forwood (December 16th 2011). Role of ACOT7 in Arachidonic Acid Production and ... Role of ACOT7 in Arachidonic Acid Production and Inflammation. By Crystall Swarbrick, Noelia Roman and Jade K. Forwood ... www.intechopen.com/embed/inflammatory-diseases-a-modern-perspective/role-of-acot7-in-arachidonic-acid-production-and- ...
... arachidonic acid; cyclooxygenase; cytochrome P-450; dihydroxyeicosatetraenoic acid; epoxyeicosatrienoic acid; ... Role of arachidonic acid metabolites on the control of non-differentiated intestinal epithelial cell growth.. Cabral M1, Martín ... Increasingly evidence indicates that enzymes, receptors and metabolites of the arachidonic acid (AA) cascade play a role in ... 12 and 15-hydroxyeicosatetraenoic acid (HETE) but not LTD4, 20-HETE and epoxyeicosatrienoic acids. We also found that ...
Antibodies for proteins involved in arachidonic acid epoxygenase activity pathways, according to their Panther/Gene Ontology ... Antibodies for proteins involved in arachidonic acid epoxygenase activity pathways; according to their Panther/Gene Ontology ...
  • It is ingested from oily fish, and algae oil or derived from dietary alpha-linolenic acid found in, for instance, walnuts, hemp oil and flax oil. (wikipedia.org)
  • Today, the usual diet in industrial countries contains much less ω-3 fatty acids than the diet of a century ago and a much greater amount of air pollution on a daily basis that evokes the inflammatory response. (wikipedia.org)
  • In response to a variety of inflammatory signals, these EFAs are cleaved out of the phospholipid and released as free fatty acids. (wikipedia.org)
  • Glutamate is the most extensively distributed excitatory amino acid neurotransmitter in the cerebral cortex. (ahajournals.org)
  • LTBR1 and LTBR2 encode for proteins with 45% amino acid identity that belong to the G protein-coupled receptor superfamily. (wikipedia.org)
  • Two BLT2-like receptors, Blt2a and Blt2b, with 49% amino acid identity to each other and 34% and 29%, respectively, amino acid identities to human BLT2 have been cloned from Zebrafish embryos. (wikipedia.org)
  • The latter citation presents a phylogenic tree on the amino acid relateness of these two receptors as well as those from humans, monkeys, dogs, rats and mice to each other. (wikipedia.org)
  • In terms of their molecular biology, COX-1 and COX-2 are of similar molecular weight, approximately 70 and 72 kDa, respectively, and having 65% amino acid sequence homology and near-identical catalytic sites. (wikipedia.org)
  • the membrane-binding domain consists of a series of amphipathic α helices with several hydrophobic amino acids exposed to a membrane monolayer. (wikipedia.org)
  • The human CysLTR1 gene maps to the X chromosome at position Xq13-Xq21, contains three exons with the entire open reading frame located in exon 3, and codes for a protein composed of 337 amino acids. (wikipedia.org)
  • Binding of calmodulin occurs between amino acids 420 and 437 in CERK at a putative 1-8-14B calmodulin binding motif. (wikipedia.org)
  • The binding motif in CERK contains leu-422, phe-429, and leu-435 which respectively correspond to the 1st, 8th, and 14th hydrophobic amino acids where calmodulin binds. (wikipedia.org)
  • Human PRKCE gene (Ensembl ID: ENSG00000171132) encodes the protein PKCε (Uniprot ID: Q02156), which is 737 amino acids in length with a molecular weight of 83.7 kDa. (wikipedia.org)
  • specifically, the C2 domain of PKCε at amino acids 14-21 (also known as εV1-2) binds RACK2, and peptide inhibitors targeting εV1-2 inhibit PKCε translocation and function in cardiomyocytes, while peptide agonists augment translocation. (wikipedia.org)
  • The originally cloned TP from placenta (343 amino acids in length) is known as the α isoform and the splice variant cloned from endothelium (with 407 amino acids), termed the β isoform. (wikipedia.org)
  • The first 328 amino acids are the same for both isoforms, but the β isoform exhibits an extended C-terminal cytoplasmic domain. (wikipedia.org)
  • ALOX12 is 75 kilodalton protein composed of 663 amino acids. (wikipedia.org)
  • This 11 kilobase pair gene consists of 14 exons and 13 introns coding for a 75 kiloDalton protein composed of 662 amino acids. (wikipedia.org)
  • The ALOX5 gene, which occupies 71.9 kilobase pairs (kb) on chromosome 10 (all other human lipoxygenases are clustered together on chromosome 17), is composed of 14 exons divided by 13 introns encoding the mature 78 kilodalton (kD) ALOX5 protein consisting of 673 amino acids. (wikipedia.org)
  • Human ALOX5 is a soluble, monomeric protein consisting of 673 amino acids with a molecular weight of ~78 kDa. (wikipedia.org)
  • This width appears to be maintained by hydrogen bonding and van der Waals forces within a sheet of aromatic amino acid residues surrounding the selectivity filter. (wikipedia.org)
  • Its 148-amino acid preproprotein, following cleavage of a signal peptide, is further processed to produce either the 27-amino acid gastrin-releasing peptide or the 10-amino acid neuromedin C. These smaller peptides regulate numerous functions of the gastrointestinal and central nervous systems, including release of gastrointestinal hormones, smooth muscle cell contraction, and epithelial cell proliferation. (wikipedia.org)
  • The current nomenclature guidelines suggest that members of new CYP families share at least 40% amino acid identity, while members of subfamilies must share at least 55% amino acid identity. (wikipedia.org)
  • citation needed] LTC4, LTD4, LTE4 and LTF4 are often called cysteinyl leukotrienes due to the presence of the amino acid cysteine in their structure. (wikipedia.org)
  • Thereafter the glucose that is released into the blood by the liver for general use by the body tissues, has to be synthesized from the glucogenic amino acids and a few other gluconeogenic substrates, which do not include fatty acids. (wikipedia.org)
  • On the basis of these results, it appears that the arachidonic acid cascade is essentially absent in Drosophila head, including the brain and compound eyes. (nih.gov)
  • This book is about the arachidonic acid cascade, its biochemistry, its pharmacology, and its roles in signal transduction. (alibris.com)
  • The effect of Pardaxin, a neurotoxin that induces neurotransmitter release from neurons, on the arachidonic acid (AA) cascade was studied in PC12 cells. (aspetjournals.org)
  • Is the brain arachidonic acid cascade a common target of drugs used to manage bipolar disorder? (biochemsoctrans.org)
  • In the present paper, I review studies in unanaesthetized rats using a neuropharmacological approach, combined with kinetic, biochemical and molecular biology techniques, demonstrating that chronic administration of three commonly used mood stabilizers (lithium, valproic acid and carbamazepine), at therapeutically relevant doses, selectively target the brain arachidonic acid cascade. (biochemsoctrans.org)
  • Arachidonic acid cascade products have been shown to be increased in vitro in Staphylococcus aureus enterotoxin B (SEB)-treated epithelial cell cultures in our laboratory. (asm.org)
  • These studies suggest that arachidonic acid cascade metabolites were a consequence of SEB intoxication and may provide a logical site for metabolic interference in SEB-induced toxicity. (asm.org)
  • It sits at the head of the "arachidonic acid cascade" - more than 20 different signalling paths that control a wide array of bodily functions, but especially those functions involving inflammation, cell growth and the central nervous system. (wikipedia.org)
  • In the inflammatory response, two other groups of dietary essential fatty acids form cascades that parallel and compete with the arachidonic acid cascade. (wikipedia.org)
  • Many of the anti-mania medications used to treat bipolar disorder work by targeting the arachidonic acid cascade in the brain. (wikipedia.org)
  • Whereas, by virtue of its exclusive location on maternal side of placental trophoblasts and its preference for long chain polyunsaturated fatty acids (LCPUFAs), placenta specific plasma membrane fatty acid-binding protein ( p-FABPpm) sequesters maternal plasma DHA/ARA to the placenta for fetal supply. (wikipedia.org)
  • CYP2C18 also possesses epoxygenase activitiy: it can attack various long-chain polyunsaturated fatty acids at their double (i.e. alkene) bonds to form epoxide products that act as signaling agents. (wikipedia.org)
  • 12-Hydroxyheptadecatrenoic acid (also termed 12-HHT, 12(S)-hydroxyheptadeca-5Z,8E,10E-trienoic acid, or 12(S)-HHTrE) is a 17 carbon metabolite of the 20 carbon polyunsaturated fatty acid, arachidonic acid. (wikipedia.org)
  • There has also been postulated the existence of LTG4, a metabolite of LTE4 in which the cysteinyl moiety has been oxidized to an alpha-keto-acid (i.e.-the cysteine has been replaced by a pyruvate). (wikipedia.org)
  • Abstract Recent evidence has suggested that arachidonic acid (AA) may be an important signaling molecule in cardiac excitation-contraction coupling. (ahajournals.org)
  • i.e., one protein can catalyze the oxidation of arachidonic acid at multiple sites. (aspetjournals.org)
  • Employing a monoclonal antibody directed against human PR3 and ANCA-positive serum from WG patients with specificity for PR3, we now investigated the role of free arachidonic acid (AA) in autoantibody-related human neutrophil activation. (rupress.org)
  • On the other hand, diets high in carbohydrate and low in fat and protein (with little or no arachidonic acid) may be associated with lower levels of anxiety and depression , according to epidemiological studies. (nutritionfacts.org)
  • Protein kinases C translocation responses to low concentrations of arachidonic acid. (springer.com)
  • Heart microsomal protein from control or isoproterenol treated rats was incubated with 50 μM arachidonic acid, and arachidonic acid metabolites were determined by liquid chromatography-electron spray ionization-mass spectrometry. (aspetjournals.org)
  • Hydroxycarboxylic acid receptor 2 (HCA2), also known as niacin receptor 1 (NIACR1) and GPR109A, is a protein which in humans is encoded by the HCAR2 gene. (wikipedia.org)
  • HCA2 is a high-affinity Gi/Go-coupled G protein-coupled receptor (GPCR) for nicotinic acid (niacin), and is a member of the nicotinic acid receptor family of GPCRs. (wikipedia.org)
  • The location of fatty acid translocase (FAT) and fatty acid transporter protein (FATP) on both sides of the bipolar placental trophoblast cells and the lack of specificity for particular types of free fatty acids (FFA) allows transport by all FFAs (non-essential, essential and long-chain PUFAs) bidirectionally, i.e. from the mother to the fetus and vice versa. (wikipedia.org)
  • When compared to other macronutrient classes (carbohydrates and protein), fatty acids yield the most ATP on an energy per gram basis, when they are completely oxidized to CO2 and water by beta oxidation and the citric acid cycle. (wikipedia.org)
  • Long chain free fatty acids enter the metabolizing cells (i.e. most living cells in the body except red blood cells and neurons in the central nervous system) through specific transport proteins, such as the SLC27 family fatty acid transport protein. (wikipedia.org)
  • In animals, as well as some fungi such as yeast, these same reactions occur on fatty acid synthase I (FASI), a large dimeric protein that has all of the enzymatic activities required to create a fatty acid. (wikipedia.org)
  • Arachidonic acid was mainly metabolised to HETEs with product levels ranging from 59.3 to 460 ng 10(-6) cells. (fraunhofer.de)
  • Figure 2) While metabolizing arachidonic acid primarily to PGG2, COX-2 also converts this fatty acid to small amounts of a racemic mixture of 15-Hydroxyicosatetraenoic acids (i.e., 15-HETEs) composed of ~22% 15(R)-HETE and ~78% 15(S)-HETE stereoisomers as well as a small amount of 11(R)-HETE. (wikipedia.org)
  • However, CYP2U1 may also contribute to the production of these two HETEs and CYP4F8 can metabolize arachidonic acid to 19-HETE while forming little or no 20-HETE. (wikipedia.org)
  • Substrate activation by longchain fatty acid. (springer.com)
  • The median of 8,9-EET and 14,15-EET was 14.5 and 17.7 ng 10(-6) cells, respectively, whereas 5,6-EET and 11,12-EET were below 2 ng 10(-6) cells in a 5-min incubation assay at a 30 microM arachidonic acid substrate concentration. (fraunhofer.de)
  • The most thoroughly studied substrate of the CYP epoxylgenases is arachidonic acid. (wikipedia.org)
  • Note that the eicosatetraenoate substrate loses one double bound to become an eicosatrienoic acid with three double bonds and that the epoxygenases typically form a mixture of R/S enantiomers at the attacked double bound position. (wikipedia.org)
  • Cellular Proteins and Their Fatty Acids in Health and Disease Human Placental Trophoblasts: Impact of Maternal Nutrition Early Nutrition and Lifestyle Factors: Effects on First Trimester Placenta Human Blood Platelet Function: Applications in Cardiovascular Health Dutta-Roy, Asim K. (wikipedia.org)
  • We exploited transgenic Arabidopsis thaliana plants (designated EP) producing eicosadienoic, eicosatrienoic, and arachidonic acid (AA), aimed at mimicking pathogen release of these compounds. (plantcell.org)