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.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.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.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.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.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.- .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)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.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.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.5-Lipoxygenase-Activating Proteins: Scaffolding proteins that play an important role in the localization and activation of 5-LIPOXYGENASE.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.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)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.Arachidonic Acids5,8,11,14-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).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)Linoleic Acids: Eighteen-carbon essential fatty acids that contain two double bonds.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).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)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.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)Flavanones: A group of FLAVONOIDS characterized with a 4-ketone.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.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.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.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.Chromatography, High Pressure Liquid: Liquid chromatographic techniques which feature high inlet pressures, high sensitivity, and high speed.Soybeans: An annual legume. The SEEDS of this plant are edible and used to produce a variety of SOY FOODS.Leukotriene Antagonists: A class of drugs designed to prevent leukotriene synthesis or activity by blocking binding at the receptor level.Prostaglandin-Endoperoxide Synthases: Enzyme complexes that catalyze the formation of PROSTAGLANDINS from the appropriate unsaturated FATTY ACIDS, molecular OXYGEN, and a reduced acceptor.Hydroxyurea: An antineoplastic agent that inhibits DNA synthesis through the inhibition of ribonucleoside diphosphate reductase.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)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.Phospholipases A: Phospholipases that hydrolyze one of the acyl groups of phosphoglycerides or glycerophosphatidates.Receptors, Leukotriene: Cell-surface receptors that bind LEUKOTRIENES with high affinity and trigger intracellular changes influencing the behavior of cells. The leukotriene receptor subtypes have been tentatively named according to their affinities for the endogenous leukotrienes LTB4; LTC4; LTD4; and LTE4.Phospholipases A2: Phospholipases that hydrolyze the acyl group attached to the 2-position of PHOSPHOGLYCERIDES.Caffeic Acids: A class of phenolic acids related to chlorogenic acid, p-coumaric acid, vanillic acid, etc., which are found in plant tissues. It is involved in plant growth regulation.Catechols: A group of 1,2-benzenediols that contain the general formula R-C6H5O2.Linolenic Acids: Eighteen-carbon essential fatty acids that contain three double bonds.Leukocytes: White blood cells. These include granular leukocytes (BASOPHILS; EOSINOPHILS; and NEUTROPHILS) as well as non-granular leukocytes (LYMPHOCYTES and MONOCYTES).Leukotriene E4: A biologically active principle of SRS-A that is formed from LEUKOTRIENE D4 via a peptidase reaction that removes the glycine residue. The biological actions of LTE4 are similar to LTC4 and LTD4. (From Dictionary of Prostaglandins and Related Compounds, 1990)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.Benzeneacetamides: Compounds based on benzeneacetamide, that are similar in structure to ACETANILIDES.Fatty Acids, Unsaturated: FATTY ACIDS in which the carbon chain contains one or more double or triple carbon-carbon bonds.Reticulocytes: Immature ERYTHROCYTES. In humans, these are ERYTHROID CELLS that have just undergone extrusion of their CELL NUCLEUS. They still contain some organelles that gradually decrease in number as the cells mature. RIBOSOMES are last to disappear. Certain staining techniques cause components of the ribosomes to precipitate into characteristic "reticulum" (not the same as the ENDOPLASMIC RETICULUM), hence the name reticulocytes.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.Epoxide Hydrolases: Enzymes that catalyze reversibly the formation of an epoxide or arene oxide from a glycol or aromatic diol, respectively.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.Receptors, Leukotriene B4: A class of cell surface leukotriene receptors with a preference for leukotriene B4. Leukotriene B4 receptor activation influences chemotaxis, chemokinesis, adherence, enzyme release, oxidative bursts, and degranulation in polymorphonuclear leukocytes. There are at least two subtypes of these receptors. Some actions are mediated through the inositol phosphate and diacylglycerol second messenger systems.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).Oxylipins: Eighteen-carbon cyclopentyl polyunsaturated fatty acids derived from ALPHA-LINOLENIC ACID via an oxidative pathway analogous to the EICOSANOIDS in animals. Biosynthesis is inhibited by SALICYLATES. A key member, jasmonic acid of PLANTS, plays a similar role to ARACHIDONIC ACID in animals.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).Cucumis sativus: A creeping annual plant species of the CUCURBITACEAE family. It has a rough succulent, trailing stem and hairy leaves with three to five pointed lobes.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.Lipoxygenases: Dioxygenases that catalyze the peroxidation of methylene-interrupted UNSATURATED FATTY ACIDS.Kinetics: The rate dynamics in chemical or physical systems.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.QuinolinesQuinacrine: 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.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.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)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)Solanum tuberosum: A plant species of the genus SOLANUM, family SOLANACEAE. The starchy roots are used as food. SOLANINE is found in green parts.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.Benzoquinones: Benzene rings which contain two ketone moieties in any position. They can be substituted in any position except at the ketone groups.Substrate Specificity: A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.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.Enzyme 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.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.5-Lipoxygenase-Activating Protein Inhibitors: Compounds that bind to and inhibit the action of 5-LIPOXYGENASE-ACTIVATING PROTEINS.Indoles: Benzopyrroles with the nitrogen at the number one carbon adjacent to the benzyl portion, in contrast to ISOINDOLES which have the nitrogen away from the six-membered ring.Leukotriene D4: One of the biologically active principles of SRS-A. It is generated from LEUKOTRIENE C4 after partial hydrolysis of the peptide chain, i.e., cleavage of the gamma-glutamyl portion. Its biological actions include stimulation of vascular and nonvascular smooth muscle, and increases in vascular permeability. (From Dictionary of Prostaglandins and Related Compounds, 1990)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.Gas Chromatography-Mass Spectrometry: A microanalytical technique combining mass spectrometry and gas chromatography for the qualitative as well as quantitative determinations of compounds.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.Cyclopentanes: A group of alicyclic hydrocarbons with the general formula R-C5H9.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.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.Nonheme Iron Proteins: Proteins, usually acting in oxidation-reduction reactions, containing iron but no porphyrin groups. (Lehninger, Principles of Biochemistry, 1993, pG-10)PyransUmbelliferones: 7-Hydroxycoumarins. Substances present in many plants, especially umbelliferae. Umbelliferones are used in sunscreen preparations and may be mutagenic. Their derivatives are used in liver therapy, as reagents, plant growth factors, sunscreens, insecticides, parasiticides, choleretics, spasmolytics, etc.Isoenzymes: Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.ZymosanDose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.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.Dioctyl Sulfosuccinic Acid: All-purpose surfactant, wetting agent, and solubilizer used in the drug, cosmetics, and food industries. It has also been used in laxatives and as cerumenolytics. It is usually administered as either the calcium, potassium, or sodium salt.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.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Cytosol: Intracellular fluid from the cytoplasm after removal of ORGANELLES and other insoluble cytoplasmic components.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.Pleurisy: INFLAMMATION of PLEURA, the lining of the LUNG. When PARIETAL PLEURA is involved, there is pleuritic CHEST PAIN.Gene Expression Regulation, Enzymologic: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis.Pyrazolones: Compounds with a five-membered heterocyclic ring with two nitrogens and a keto OXYGEN. Some are inhibitors of TNF-ALPHA production.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)Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.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.Spectrophotometry, Ultraviolet: Determination of the spectra of ultraviolet absorption by specific molecules in gases or liquids, for example Cl2, SO2, NO2, CS2, ozone, mercury vapor, and various unsaturated compounds. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)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.)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.Seeds: The encapsulated embryos of flowering plants. They are used as is or for animal feed because of the high content of concentrated nutrients like starches, proteins, and fats. Rapeseed, cottonseed, and sunflower seed are also produced for the oils (fats) they yield.Cyclooxygenase 1: A constitutively-expressed subtype of prostaglandin-endoperoxide synthase. It plays an important role in many cellular processes.CycloheptanesIonophores: 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.Cell Line: Established cell cultures that have the potential to propagate indefinitely.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.Monocytes: Large, phagocytic mononuclear leukocytes produced in the vertebrate BONE MARROW and released into the BLOOD; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles.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.
(1/135) Reactive oxygen intermediate-dependent NF-kappaB activation by interleukin-1beta requires 5-lipoxygenase or NADPH oxidase activity.

We previously reported that the role of reactive oxygen intermediates (ROIs) in NF-kappaB activation by proinflammatory cytokines was cell specific. However, the sources for ROIs in various cell types are yet to be determined and might include 5-lipoxygenase (5-LOX) and NADPH oxidase. 5-LOX and 5-LOX activating protein (FLAP) are coexpressed in lymphoid cells but not in monocytic or epithelial cells. Stimulation of lymphoid cells with interleukin-1beta (IL-1beta) led to ROI production and NF-kappaB activation, which could both be blocked by antioxidants or FLAP inhibitors, confirming that 5-LOX was the source of ROIs and was required for NF-kappaB activation in these cells. IL-1beta stimulation of epithelial cells did not generate any ROIs and NF-kappaB induction was not influenced by 5-LOX inhibitors. However, reintroduction of a functional 5-LOX system in these cells allowed ROI production and 5-LOX-dependent NF-kappaB activation. In monocytic cells, IL-1beta treatment led to a production of ROIs which is independent of the 5-LOX enzyme but requires the NADPH oxidase activity. This pathway involves the Rac1 and Cdc42 GTPases, two enzymes which are not required for NF-kappaB activation by IL-1beta in epithelial cells. In conclusion, three different cell-specific pathways lead to NF-kappaB activation by IL-1beta: a pathway dependent on ROI production by 5-LOX in lymphoid cells, an ROI- and 5-LOX-independent pathway in epithelial cells, and a pathway requiring ROI production by NADPH oxidase in monocytic cells.  (+info)

(2/135) Relationship of arachidonic acid metabolizing enzyme expression in epithelial cancer cell lines to the growth effect of selective biochemical inhibitors.

Arachidonic acid (AA) metabolizing enzymes are emerging as significant mediators of growth stimulation for epithelial cells. The relative contribution of the various family members of AA metabolizing enzymes to epithelial cancer cell growth is not known. To study this question, we first analyzed a series of epithelial cancer cells to establish the relative frequency of expression for the various enzymes. We analyzed the expression of five AA metabolizing enzymes as well as 5-lipoxygenase activating protein (FLAP) in a panel of human epithelial cancer cell lines (n = 20) using reverse transcription-PCR. From this analysis, we found that cyclooxygenase-1 (COX-1), 5-lipoxygenase (5-LOX), and FLAP were universally expressed in all cancer cell lines tested. For the remaining enzymes, the expression of COX-2, 12-LOX, and 15-LOX varied among cell lines, 60, 35, and 90%, respectively. Although the pattern of expression varied among the different cell types, all of the enzymes were expressed in all major cancer histologies. Using a panel of selective biochemical AA metabolizing enzyme inhibitors, we then evaluated the effect of these agents on cell lines with known expression status for the AA metabolizing enzymes. For the enzymes that were not universally expressed, growth inhibition by selective biochemical inhibitors did not closely correlate with the expression status of specific enzymes (P > 0.05). For the universally expressed enzymes, the LOX inhibitors were more potent growth inhibitors than the COX inhibitors. The frequent expression of the AA metabolizing enzymes suggests that AA metabolism pathway may be modulated in response to xenobiotic exposure during carcinogenesis. Although establishing a priori AA metabolizing enzyme status was not consistently informative about what AA metabolizing enzyme inhibition would be most growth inhibitory, the frequent inhibition of many epithelial cancers by these biochemical inhibitors opens a new avenue for cancer therapy and intervention in carcinogenesis.  (+info)

(3/135) The 5-lipoxygenase-activating protein (FLAP) inhibitor, MK886, induces apoptosis independently of FLAP.

The ability of various inhibitors of lipoxygenase (LOX) enzymes and 5-lipoxygenase-activating protein (FLAP) to induce apoptosis has implicated these pathways in the mechanism(s) of this form of cell death. Although FLAP plays an important role in 5-LOX activity, this protein is found at high levels in some cells lacking LOX, suggesting it might mediate other effects. Furthermore, the concentration of MK886, a FLAP inhibitor, required to induce apoptosis is approximately 100-fold more than that required to inhibit LOX, and this compound remains effective in cells lacking LOX. The present study examines the role of FLAP in MK886-induced apoptosis. MK886 induced apoptosis in WSU cells, a human chronic lymphocytic leukaemia cell line that lacks FLAP protein and mRNA, suggesting that this agent is acting independently of FLAP. This conclusion was further supported by the fact that a more specific FLAP inhibitor, MK591, induced only minimal apoptosis in FL5.12 cells, a murine prolymphoid cell line containing FLAP. The role of FLAP was examined more directly by decreasing its expression by more than 50% in FL5.12 cells treated with 10 microM of an antisense oligonucleotide for 48h. This change in FLAP was not accompanied by any increase in apoptosis. Furthermore, FLAP-depleted cells exhibited the same level of apoptosis 8 h after treatment with 10 microM MK886, as did control cells. The increased fluorescence seen in MK886-treated cells loaded with carboxydichlorofluorescein indicates that oxidative reactions are stimulated by this compound, possibly via the release of fatty acids from fatty acid-binding proteins and their subsequent oxidation.  (+info)

(4/135) Expression of 5-lipoxygenase and 5-lipoxygenase-activating protein in human fetal membranes throughout pregnancy and at term.

Lipoxygenase metabolites may be involved in human parturition. 5-lipoxygenase (5-LOX) catalyses the first steps in the synthesis of leukotrienes from arachidonic acid, and its activity is dependent on 5-LOX activating protein (FLAP). The expression of 5-LOX and FLAP were investigated in fetal membranes to determine whether there are changes with gestational age or at term with the onset of labour. No significant differences were found in the expression of 5-LOX or FLAP mRNA in the amnion at different gestational ages or at term. In the chorion-decidua, 5-LOX mRNA expression was significantly higher in the first trimester of pregnancy than in the second and third trimesters. At term, there was a significant increase in both 5-LOX mRNA and protein expression in the chorion-decidua in the time after labour, compared with the time before labour. The expression of FLAP mRNA was also significantly higher in the chorion-decidua in the first trimester of pregnancy compared with the third trimester, and at term in the time after labour compared with the time before labour. Expression of FLAP protein was not studied, as an antibody is not currently available. These results are consistent with a role for 5-LOX and FLAP in the control of parturition at term, and also suggest an involvement earlier in pregnancy.  (+info)

(5/135) IL-5 increases expression of 5-lipoxygenase-activating protein and translocates 5-lipoxygenase to the nucleus in human blood eosinophils.

Cysteinyl-leukotrienes are potent bronchoconstrictor mediators synthesized by the 5-lipoxygenase (5-LO) pathway. Eosinophilopoietic cytokines such as IL-5 enhance cysteinyl-leukotriene synthesis in eosinophils in vitro, mimicking changes in eosinophils from asthmatic patients, but the mechanism is unknown. We hypothesized that IL-5 induces the expression of 5-LO and/or its activating protein FLAP in eosinophils, and that this might be modulated by anti-inflammatory corticosteroids. Compared with control cultures, IL-5 increased the proportion of normal blood eosinophils immunostaining for FLAP (65 +/- 4 vs 34 +/- 4%; p < 0.0001), enhanced immunoblot levels of FLAP by 51 +/- 14% (p = 0.03), and quadrupled ionophore-stimulated leukotriene C4 synthesis from 5.7 to 20.8 ng/106 cells (p < 0.02). IL-5 effects persisted for 24 h and were abolished by cycloheximide and actinomycin D. The proportion of FLAP+ eosinophils was also increased by dexamethasone (p < 0.0001). Neither IL-5 nor dexamethasone altered 5-LO expression, but IL-5 significantly increased 5-LO immunofluorescence localizing to eosinophil nuclei. Compared with normal subjects, allergic asthmatic patients had a greater proportion of circulating FLAP+ eosinophils (46 +/- 6 vs 27 +/- 3%; p < 0.03) and a smaller IL-5-induced increase in FLAP immunoreactivity (p < 0.05). Thus, IL-5 increases FLAP expression and translocates 5-LO to the nucleus in normal blood eosinophils in vitro. This is associated with an enhanced capacity for cysteinyl-leukotriene synthesis and mimics in vivo increases in FLAP expression in eosinophils from allergic asthmatics.  (+info)

(6/135) Increased cyclooxygenase-2 and 5-lipoxygenase activating protein expression in peritoneal macrophages during ovalbumin immunization of mice and cytosolic phospholipase A(2) activation after antigen challenge.

The present study investigates phenotypic and functional differentiation of peritoneal macrophages during ovalbumin-induced subcutaneous immunization of mice. For the first time we show that, in mouse peritoneal macrophages, ovalbumin immunization induces an increase in cyclooxygenase-2 (COX-2) and 5-lipoxygenase activating protein (FLAP) expression whereas it inhibits cytosolic phospholipase A(2) (cPLA2) expression. The study of arachidonic acid (AA) metabolism in peritoneal macrophages from control (cPM) and ovalbumin-immunized (iPM) mice shows that the reduced cPLA2 expression is correlated to a reduced basal AA metabolism, but is not a limiting factor for the opsonized zymosan-, PMA-, or A23187-triggered AA metabolism. We also show that in vitro ovalbumin challenge induces, only in iPM, cPLA2 activation through phosphorylation of serine residues, via a mechanism involving MAP kinases, and through increased intracellular calcium concentrations, leading to eicosanoid production. In parallel, we report that, in peritoneal macrophages, ovalbumin immunization induces the expression of CD23, the low affinity receptor for IgEs known for its involvement in allergic diseases. Thus, the modified expression of the enzymes involved in AA metabolism and the difference of response of cPM and iPM toward the antigen are important elements to understand the underlying mechanisms of ovalbumin-induced allergic responses.  (+info)

(7/135) Prolonged exposure to lipopolysaccharide inhibits macrophage 5-lipoxygenase metabolism via induction of nitric oxide synthesis.

LPS from bacteria can result in the development of sepsis syndrome and acute lung injury. Although acute exposure to endotoxin primes leukocytes for enhanced synthesis of leukotrienes (LT), little is known about the effect of chronic exposure. Therefore, we determined the effect of prolonged LPS treatment on 5-lipoxygenase (5-LO) metabolism of arachidonic acid in alveolar macrophages (AM) and in peripheral blood monocytes. Pretreatment of AM with LPS caused time- and dose-dependent suppression of LT synthetic capacity. LPS pretreatment failed to inhibit arachidonic acid (AA) release. The fact that LPS inhibited LT synthesis from endogenous AA more than from exogenous AA suggested an effect on 5-LO-activating protein (FLAP). In addition, an inhibitory effect of LPS treatment on AM 5-LO activity was suggested by cell-free 5-LO enzyme assay. No effect on the expression of either 5-LO or FLAP proteins was observed. New protein synthesis was necessary for LPS-induced reduction of 5-LO metabolism in AM, and immunoblotting demonstrated marked induction of NO synthase (NOS). Inhibition by LPS was reproduced by an NO donor and was abrogated by inhibitors of constitutive and inducible NOS. Compared with AM, peripheral blood monocytes exhibited no suppression by LPS of 5-LO metabolism and no induction of inducible NOS. We conclude that prolonged exposure to LPS impairs AM 5-LO metabolism by NO-mediated suppression of both 5-LO and FLAP function. Because LT contribute to antimicrobial defense, this down-regulation of 5-LO metabolism may contribute to the increased susceptibility to pneumonia in patients following sepsis.  (+info)

(8/135) In situ amplification of 5-lipoxygenase and 5-lipoxygenase-activating protein in allergic airway inflammation and inhibition by leukotriene blockade.

Leukotrienes are important mediators of the eosinophilic influx and mucus hypersecretion in the lungs in a murine model of asthma. We used in situ PCR in this model of human asthma to detect lung mRNA for 5-lipoxygenase (5-LO) and 5-LO-activating protein (FLAP), key proteins necessary for leukotriene synthesis. Lung tissue was obtained on day 28 from mice treated with i.p. (days 0 and 14) and intranasal (days 14, 25, 26, and 27) OVA or saline. After fixation, the tissue sections underwent protease- and RNase-free DNase digestion, before in situ RT-PCR using target-specific cDNA amplification. 5-LO and FLAP-specific mRNA was visualized by a digoxigenin detection system, and positive cells were analyzed by morphometry. 5-LO and FLAP-specific mRNA and protein were associated primarily with eosinophils and alveolar macrophages in the airways and pulmonary blood vessels in OVA-sensitized/challenged mice. 5-LO and FLAP protein expression increased on a per-cell basis in alveolar macrophages of OVA-treated mice compared with saline controls. Pulmonary blood vessel endothelial cells were also positive for 5-LO, FLAP mRNA, and protein. 5-LO inhibition significantly decreased 5-LO and FLAP-specific mRNA and protein expression in the lung inflammatory cells and endothelial cells. These studies demonstrate a marked increase in key 5-LO pathway proteins in the allergic lung inflammatory response and an important immunomodulatory effect of leukotriene blockade to decrease 5-LO and FLAP gene expression.  (+info)

*  Lipoxygenase
... rabbit 15-lipoxygenase and porcine leukocyte 12-lipoxygenase catalytic domain. The protein consists of a small N-terminal PLAT ... and thereby are key regulators in the formation of lipoxygenase-dependent metabolites. In addition, cells, when so activated, ... erythrocyte type 15-lipoxygenase (or 15-lipoxygenase, erythrocyte type), reticulocyte type 15-lipoxygenase (or 15-lipoxygenase ... There are several lipoxygenase structures known including: soybean lipoxygenase L1 and L3, coral 8-lipoxygenase, human 5- ...
*  15-Hydroxyeicosatetraenoic acid
15(S)-HpETE and 15(S)-HETE bind to and activate the G protein-coupled receptor, Leukotriene B4 receptor 2, i.e. BLT2. This ... 15-Lipoxygenase-1: Cells metabolize arachidonic acid with 15-lipoxygenase-1 (i.e., 15-LO-1, ALOX15) to form 15(S)-HpETE as a ... They may use a similar "protein-adduction" mechanism; if so the target protein(s) for these effects have not been defined or ... 15(S)-HpETE and 15(S)-HETE also directly bind with and activate peroxisome proliferator-activated receptor gamma. This ...
*  5-lipoxygenase-activating protein
How FLAP activates 5-lipooxygenase is not completely understood, but there is a physical interaction between the two. FLAP ... It is an integral protein within the nuclear membrane. FLAP is necessary in synthesis of leukotriene, which are lipid mediators ... Leukotrienes, which need the FLAP protein to be made, have an established pathological role in allergic and respiratory ... is a protein that in humans is encoded by the ALOX5AP gene. FLAP is necessary for the activation of 5-lipoxygenase and ...
*  AM-679 (FLAP inhibitor)
This protein is involved in the production of cysteinyl leukotrienes which are involved in inflammation, and AM-679 has anti- ... Part 2: 3-{5-((S)-1-Acetyl-2,3-dihydro-1H-indol-2-ylmethoxy)-3-tert-butylsulfanyl-1-[4-(5-methoxy-pyrimidin-2-yl)-benzyl]-1H- ... Musiyenko, A.; Correa, L.; Stock, N.; Hutchinson, J. H.; Lorrain, D. S.; Bain, G.; Evans, J. F.; Barik, S. (2009). "A Novel 5- ... Lipoxygenase-Activating Protein Inhibitor, AM679, Reduces Inflammation in the Respiratory Syncytial Virus-Infected Mouse Eye". ...
*  MAPEG family
In molecular biology the MAPEG (Membrane-Associated Proteins in Eicosanoid and Glutathione metabolism) family of proteins are a ... Protein Science. 8 (3): 689-692. doi:10.1110/ps.8.3.689. PMC 2144274 . PMID 10091672. This article incorporates text from the ... "Common structural features of mapeg-a widespread superfamily of membrane associated proteins with highly divergent functions in ... "Crystal structure of a human membrane protein involved in cysteinyl leukotriene biosynthesis". Nature. 448 (7153): 609-612. doi ...
*  L 663536
"Inhibition of five lipoxygenase activating protein (FLAP) by MK-886 decreases atherosclerosis in apoE/LDLR-double knockout mice ... Jun, Joon-Il; Lau, Lester F. (July 2010). "The matricellular protein CCN1 induces fibroblast senescence and restricts fibrosis ... It may perform this by blocking the 5-lipoxygenase activating protein (FLAP), thus inhibiting 5-lipoxygenase (5-LOX), and may ...
*  Essential fatty acid interactions
Other lipoxygenases-8-LO, 12-LO and 15-LO-make other eicosanoid-like products. To act, 5-LO uses the nuclear-membrane enzyme 5- ... lipoxygenase-activating protein (FLAP), first to a hydroperoxyeicosatetraenoic acid (HPETE), then to the first leuokotriene, ... They activate phospholipidase to release AA from neuron cell membranes as a free fatty acid. During its short lifespan, free AA ... Lipoxygenase oxidation removes no C=C double bonds, and leads to the LK. After oxidation, the eicosanoids are further modified ...
*  Leukotriene C4 synthase
"Protein-protein interaction affinity chromatography of leukotriene C4 synthase". Protein Expr. Purif. 6 (3): 352-6. doi:10.1006 ... This protein is remotely related to microsomal glutathione S-transferase. The MAPEG (Membrane-Associated Proteins in Eicosanoid ... 2000). "Membrane-associated proteins in eicosanoid and glutathione metabolism (MAPEG). A widespread protein superfamily". Am. J ... The protein encoded by this gene, LTC4S (or glutathione S-transferase II) is an enzyme that converts leukotriene A4 and ...
*  Leukotriene C4
All three leukotrienes then bind at different affinities to two G-protein coupled receptors: CYSLTR1 and CYSLTR2, triggering ... doi:10.1016/b978-0-12-394300-2.00002-8. Haeggström, Jesper Z.; Funk, Colin D. (2011-09-22). "Lipoxygenase and Leukotriene ... stress and chemotherapy induce LTC4 biosynthesis by transcriptionally upregulating and activating the enzyme microsomal ... 5-lipoxygenase-activating protein (FLAP) and LTC4 synthase (LTC4S), which couples glutathione to an LTA4 intermediate.The MRP1 ...
*  MGST2
2000). "Membrane-associated proteins in eicosanoid and glutathione metabolism (MAPEG). A widespread protein superfamily". Am. J ... The MAPEG (Membrane-Associated Proteins in Eicosanoid and Glutathione metabolism) family consists of six human proteins, ... This gene encodes a protein that catalyzes the conjugation of leukotriene A4 and reduced glutathione to produce leukotriene C4 ... 161 (2 Pt 2): S20-4. doi:10.1164/ajrccm.161.supplement_1.ltta-5. PMID 10673221. Hillier LD, Lennon G, Becker M, et al. (1997 ...
*  Antileukotriene
"Inhibition of five lipoxygenase activating protein (FLAP) by MK-886 decreases atherosclerosis in apoE/LDLR-double knockout mice ... strong downregulation of CXCR3 expression on activated T cells, and downregulation of matrix metalloproteinase 9 expression ... Examples of 5-LOX inhibitors include drugs, such as meclofenamate sodium and zileuton. Some chemicals found in trace amounts in ... 188 (5): 538-544. doi:10.1164/rccm.201301-0023PP. PMID 23822826. Singh, Rakesh Kumar; Tandon, Ruchi; Dastidar, Sunanda Ghosh; ...
*  Leukotriene
When such cells are activated, arachidonic acid is liberated from cell membrane phospholipids by phospholipase A2, and donated ... The lipoxygenase pathway is active in leukocytes and other immunocompetent cells, including mast cells, eosinophils, ... Leukotrienes act principally on a subfamily of G protein-coupled receptors. They may also act upon peroxisome proliferator- ... activated receptors. Leukotrienes are involved in asthmatic and allergic reactions and act to sustain inflammatory reactions. ...
*  Arachidonate 5-lipoxygenase
... and/or 271 by Mitogen-activated protein kinases, S6 kinase, protein kinase A (PKA), protein kinase C, Cdc2, and/or a Ca2+/ ... ALOX5 binds with the F actin-binding protein, coactin-like protein. Based on in vitro studies, this protein binding serves to ... This chemotactic factor stimulation concurrently causes the activation of mitogen-activated protein kinases (MAPK) which in ... Coactin-like protein (COL1), and Dicer protein A PLAT domain within its C2-like domain; this domain, by analogy to other PLAT ...
*  Acne
Squalene oxidation activates NF-κB (a protein complex) and consequently increases IL-1α levels. Additionally, squalene ... LTB4 promotes skin inflammation by acting on the peroxisome proliferator-activated receptor alpha (PPARα) protein. PPARα ... Milk contains whey protein and hormones such as bovine IGF-1 and precursors of dihydrotestosterone. These components are ... A major mechanism of acne-related skin inflammation is mediated by P. acnes's ability to bind and activate a class of immune ...
*  12-Hydroxyheptadecatrienoic acid
... activate cells by releasing the Gq alpha subunit and pertussis toxin-sensitive Gi alpha subunit from Heterotrimeric G proteins ... and lipoxygenase-derived eicosanoids". Drug Metabolism and Disposition. 39 (2): 180-90. doi:10.1124/dmd.110.035121. PMC 3033693 ... but also bound and was activated by a wide range of peptides, proteins, and other agents. BLT2 may ultimately prove to have ... It activates cells through both its high affinity (Dissociation constant [Kd] of 0.5-1.5 nM) Leukotriene B4 receptor 1 (BLT1 ...
*  ALOX12
... cyclic adenosine monophosphate response element-binding protein phosphorylation, and p38 mitogen-activated protein kinase ... ALOX12 (EC 1.13.11.31), also known as arachidonate 12-lipoxygenase, 12-lipoxygenase, 12S-Lipoxygenase, 12-LOX, and 12S-LOX is a ... Delta12-lipoxygenase, 12Delta-lipoxygenase, C-12 lipoxygenase, leukotriene A4 synthase, and LTA4 synthase. ALOX12, often termed ... Tang K, Finley RL, Nie D, Honn KV (March 2000). "Identification of 12-lipoxygenase interaction with cellular proteins by yeast ...
*  Chromosome 10 (human)
... rho GTPase activating protein 21 ARID5B: encoding protein AT-rich interactive domain-containing protein 5B AS3MT: encoding ... encoding protein Arginine vasopressin-induced protein 1 C10orf118: encoding protein Uncharacterized protein C10orf118 C10orf67 ... WW domain binding protein 1-like ZNF37A: zinc finger protein 37A ZNF438: zinc finger protein 438 The following diseases are ... STAM binding protein like 1 STOX1: encoding protein Storkhead box 1 SUPV3L1: Suv3 like RNA helicase TACC2 encoding protein ...
*  Actin-binding protein
... p21-activated Kinase) Plectin p47PHOX Parvin (actopaxin) Prefoldin p53 PASK (Proline, Alanine rich Ste20 related Kinase) ... Actin-binding proteins (also known as ABP) are proteins that bind to actin. This may mean ability to bind actin monomers, or ... This is a list of actin-binding proteins in alphabetical order. List: 0-9 A B C D E F G H I J K L M N O P Q R S T U V W x Y Z ... Profilin p185neu Ponticulin Protein kinase C Porin P.IB Prk1p (actin regulating kinase) Radixin (the R of ERM proteins) Rapsyn ...
*  Leukotriene B4 receptor 2
BLT2 receptors, similar to BLT1 receptors, are G protein coupled receptors that, when ligand-bound, activate G proteins that ... Finally, 12-lipoxygenase is overexpressed and the mass of 12-HETE is far higher in human prostate cancer than nearby normal ... "Induction of cyclooxygenase-2 by activated Ha-ras oncogene in Rat-1 fibroblasts and the role of mitogen-activated protein ... thereby activating calcium-activated intracellular signaling molecules; it also stimulates cells to activate Extracellular ...
*  GRB2
Linker of activated T cells, Lymphocyte cytosolic protein 2, MAP2, MAP3K1 MAP4K1, MED28, MST1R, MUC1, Mitogen-activated protein ... "Induced direct binding of the adapter protein Nck to the GTPase-activating protein-associated protein p62 by epidermal growth ... the guanine nucleotide exchange protein Sos and a 75-kDa protein that is a substrate for T cell antigen receptor-activated ... "The protein product of the c-cbl protooncogene is the 120-kDa tyrosine-phosphorylated protein in Jurkat cells activated via the ...
*  Neutrophil extracellular traps
Furthermore, delivering the granule proteins into NETs may keep potentially injurious proteins like proteases from diffusing ... The end result of the process then depends on which NETosis pathway is activated. Suicidal NETosis was first described in a ... The formation of NETs is regulated by the lipoxygenase pathway - during certain forms of activation (including contact with ... tubulin and various other cytoplasmatic proteins are not present in NETs. NETs disarm pathogens with antimicrobial proteins ...
*  5-Hydroxyeicosatetraenoic acid
... p38 mitogen-activated protein kinases, cytosolic phospholipase A2, PI3K/Akt, and protein kinase C beta and epsilon. The ... 12-Lipoxygenase (i.e. ALOX12) to metabolize 5(S)-HETE to 5(S),12(S)-diHETE. The activity of this product has not yet been fully ... HETE family stimulate cells primarily by binding and thereby activating a dedicated G protein-coupled receptor, the ... protein complex to dissociate into its Gαi and Gβγ components with Gβγ appearing to be the component responsible for activating ...
*  Arachidonic acid
ARA also activates syntaxin-3 (STX-3), a protein involved in the growth and repair of neurons. Arachidonic acid is also ... The enzymes 15-lipoxygenase-1 (ALOX15 and 15-lipoxygenase-2 (ALOX15B metabolize arachidonic acid to 15- ... It also helps protect the brain from oxidative stress by activating peroxisome proliferator-activated receptor gamma. ... Receptors that activate this pathway include: A1 receptor D2 receptor α-2 adrenergic receptor 5-HT1 receptor PLC may also be ...
*  Epoxygenase
... metabolites many of which act on cells by binding with and thereby activating specific and well-characterized receptor proteins ... Finally, there are relatively few metabolite-forming lipoxygenases and cyclooxygenases in the first and second pathways and ... Proteins and Proteomics. 1814 (1): 210-22. doi:10.1016/j.bbapap.2010.09.009. PMID 20869469. Moran, J. H.; Weise, R; Schnellmann ... "RTX proteins: A highly diverse family secreted by a common mechanism". FEMS Microbiology Reviews. 34 (6): 1076-112. doi:10.1111 ...
*  TRIB1
2004). "Human tribbles, a protein family controlling mitogen-activated protein kinase cascades". J. Biol. Chem. 279 (41): 42703 ... Tang K, Finley RL, Nie D, Honn KV (2000). "Identification of 12-lipoxygenase interaction with cellular proteins by yeast two- ... The protein's primary structure contains a PEST region, indicative of proteins that are highly susceptible to degradation in ... Tribbles homolog 1 is a protein kinase that in humans is encoded by the TRIB1 gene. Orthologs of this protein pseudokinase ( ...
*  Prostate cancer
The protein ZIP1 is responsible for the active transport of zinc into prostate cells. One of the zinc's important roles is to ... AR, an androgen-activated transcription factor, belongs to the steroid nuclear receptor family. Development of the prostate is ... This protein is overexpressed in prostate cancer tissues and is associated with a higher Gleason score. Tissue samples can be ... The absence of zinc is thought to occur via a silencing of the gene that produces the transporter protein ZIP1. ZIP1 is now ...
*  ALOX12B
Tang K, Finley RL, Nie D, Honn KV (March 2000). "Identification of 12-lipoxygenase interaction with cellular proteins by yeast ... "Epidermal lipoxygenase products of the hepoxilin pathway selectively activate the nuclear receptor PPARalpha". Lipids. 42 (6): ... Arachidonate 12-lipoxygenase, 12R type, also known as ALOX12B, 12R-LOX, and arachiconate lipoygenase 3, is a lipoxygenase-type ... ALOX12B arachidonate 12-lipoxygenase, 12R type". Boeglin WE, Kim RB, Brash AR (June 1998). "A 12R-lipoxygenase in human skin: ...
Metabolites  | Free Full-Text | Targeted Chiral Analysis of Bioactive Arachidonic Acid Metabolites Using Liquid-Chromatography...  Metabolites | Free Full-Text | Targeted Chiral Analysis of Bioactive Arachidonic Acid Metabolites Using Liquid-Chromatography...
Membrane translocation of 15-lipoxygenase in hematopoietic cells is calcium-dependent and activates the oxygenase activity of ... Requirement for protein synthesis. J. Biol. Chem. 1977, 252, 1408-1413. [Google Scholar] ... Tumor-associated macrophages mediate immunosuppression in the renal cancer microenvironment by activating the 15-lipoxygenase-2 ... In contrast to PGE2 and PGD2, 15(S)-HETE and 11(R)-HETE are activated by 15-PGDH-mediated oxidation to 15-oxo-ETE and 11-oxo- ...
more infohttp://www.mdpi.com/2218-1989/2/2/337/htm
anti-FLAP antibody, Internal  | GeneTex  anti-FLAP antibody, Internal | GeneTex
... arachidonate 5-lipoxygenase-activating protein) for IHC-P, WB. Anti-FLAP pAb (GTX89246) is tested in Human samples. 100% Ab- ... MK-886-binding protein, FLAP / ALOX5AP (internal), ALOX5AP, five-lipoxygenase activating protein, MK 886 binding protein. ... fivelipoxygenase activating protein, arachidonate5lipoxygenaseactivating protein, arachidonate 5lipoxygenaseactivating, ... Primary Antibodies Secondary Antibodies Proteins & Peptides Lysates & Slides Serum & Reagents Research Kits Isotype Controls ...
more infohttp://www.genetex.com/FLAP-ALOX5AP-antibody-Internal-GTX89246.html
ASPIRIN the only NSAID that doesnt cause hardening of the arteries  ASPIRIN the only NSAID that doesn't cause hardening of the arteries
NO activates prostacyclin synthase and suppresses thromboxane synthase, likely by nitrosylating bound heme.45 In addition, NO ... Funk CD, Cyrus T. 12/15-lipoxygenase, oxidative modification of LDL and atherogenesis. Trends Cardiovasc Med. 2001; 11: 116-124 ... Venugopal SK, Devaraj S, Jialal I. C-reactive protein decreases prostacyclin release from human aortic endothelial cells. ... Interactions of nitric oxide-derived reactive nitrogen species with peroxidases and lipoxygenases. Free Radic Res. 2001; 35: ...
more infohttp://healthfully.org/id9.html
JCI -
Leukotrienes and sex: strange bedfellows?  JCI - Leukotrienes and sex: strange bedfellows?
One area that Pace and colleagues did not explore is how androgens may alter the interaction between 5-LO and FLAP. Nonetheless ... Rask-Madsen J, Bukhave K, Laursen LS, Lauritsen K. 5-Lipoxygenase inhibitors for the treatment of inflammatory bowel disease. ... Additionally, androgens inhibited the tight assembly, and drugs that directly interfered with FLAP and 5-LO/FLAP assembly were ... 5), inflammatory bowel disease (6), and acute respiratory distress syndrome (7). However, with rare exceptions, such as AERD (8 ...
more infohttps://j8k9.com.www.mobile.jci.org/articles/view/95717
THE BI-MONTHLY JOURNAL OF THE BWW SOCIETY  THE BI-MONTHLY JOURNAL OF THE BWW SOCIETY
Activated leukocyte produce H3O3, leading platelet aggregation.. More over activated leukocytes produce LTA4and LTB4in platelet ... A recent study has shown that C-reactive protein or numbers of leukocytes, a marker of inflammation, was a story predictor of ... Activated platelet may receive LTA4 from PMN leukocyte ,using transcellular biosynthesis, and produce LTC4.4 LTC4and its ... 3 Activate platelets produce p-selectin which gathers and activates leukocyte. Leucocyte tethering and rolling has been ...
more infohttp://www.bwwsociety.org/journal/archive/neurology.htm
5-lipoxygenase-activating protein - Wikipedia  5-lipoxygenase-activating protein - Wikipedia
How FLAP activates 5-lipooxygenase is not completely understood, but there is a physical interaction between the two. FLAP ... It is an integral protein within the nuclear membrane. FLAP is necessary in synthesis of leukotriene, which are lipid mediators ... Leukotrienes, which need the FLAP protein to be made, have an established pathological role in allergic and respiratory ... is a protein that in humans is encoded by the ALOX5AP gene. FLAP is necessary for the activation of 5-lipoxygenase and ...
more infohttps://en.wikipedia.org/wiki/5-lipoxygenase-activating_protein
5-Lipoxygenase-Activating Proteins | Harvard Catalyst Profiles | Harvard Catalyst  5-Lipoxygenase-Activating Proteins | Harvard Catalyst Profiles | Harvard Catalyst
Scaffolding proteins that play an important role in the localization and activation of 5-LIPOXYGENASE. ... Genetic variation in the lipoxygenase pathway and risk of colorectal neoplasia. Genes Chromosomes Cancer. 2013 May; 52(5):437- ... "5-Lipoxygenase-Activating Proteins" is a descriptor in the National Library of Medicine's controlled vocabulary thesaurus, MeSH ... This graph shows the total number of publications written about "5-Lipoxygenase-Activating Proteins" by people in Harvard ...
more infohttps://connects.catalyst.harvard.edu/Profiles/display/Concept/5-Lipoxygenase-Activating%20Proteins
5-Lipoxygenase Activating Protein Signals Adipose Tissue Inflammation and Lipid Dysfunction in Experimental Obesity | The...  5-Lipoxygenase Activating Protein Signals Adipose Tissue Inflammation and Lipid Dysfunction in Experimental Obesity | The...
Interestingly, FLAP inhibition induced AMP-activated protein kinase phosphorylation in parallel with decreases in hormone- ... 5-Lipoxygenase Activating Protein Signals Adipose Tissue Inflammation and Lipid Dysfunction in Experimental Obesity. Raquel ... Constitutive expression of key components of the 5-LO pathway, as well as leukotriene (LT) receptors, was detected in adipose ... In addition, LTB4, but not LTD4, reduced FFA uptake in primary adipocytes, whereas 5-LO inhibition suppressed isoproterenol- ...
more infohttp://www.jimmunol.org/content/early/2010/03/05/jimmunol.0901355
Attenuation of early and late phase allergen-induced bronchoconstriction in asthmatic subjects by a 5-lipoxygenase activating...  Attenuation of early and late phase allergen-induced bronchoconstriction in asthmatic subjects by a 5-lipoxygenase activating...
Attenuation of early and late phase allergen-induced bronchoconstriction in asthmatic subjects by a 5-lipoxygenase activating ... Attenuation of early and late phase allergen-induced bronchoconstriction in asthmatic subjects by a 5-lipoxygenase activating ... The effects of pretreatment with BAYx 1005, an inhibitor of leukotriene biosynthesis via antagonism of 5-lipoxygenase ... activating protein, on allergen-induced early and late asthmatic responses has been evaluated. METHODS: Eight atopic subjects ...
more infohttp://thorax.bmj.com/content/52/4/348
Leicester Research Archive: The gene encoding 5-lipoxygenase activating protein confers risk of myocardial infarction and...  Leicester Research Archive: The gene encoding 5-lipoxygenase activating protein confers risk of myocardial infarction and...
The gene encoding 5-lipoxygenase activating protein confers risk of myocardial infarction and stroke. ... A four-marker single-nucleotide polymorphism (SNP) haplotype in this locus spanning the gene ALOX5AP encoding 5-lipoxygenase ... activating protein (FLAP) is associated with a two times greater risk of myocardial infarction in Iceland. This haplotype also ... Stimulated neutrophils from individuals with myocardial infarction produce more leukotriene B4, a key product in the 5- ...
more infohttps://lra.le.ac.uk/handle/2381/17609
Arachidonate 5-lipoxygenase-activating protein  Arachidonate 5-lipoxygenase-activating protein
This protein localizes to the plasma membrane. Inhibitors of its function impede translocation of 5-lipoxygenase from the ... L 663536 results in decreased activity of ALOX5AP protein] 1 Inflammation mediated by chemokine and cytokine signaling pathway ... 2-(4-(quinolin-2-yl-methoxy)phenyl)-2-cyclopentylacetic acid results in decreased activity of ALOX5AP protein] 1 ... This gene encodes a protein which, with 5-lipoxygenase, is required for leukotriene synthesis. Leukotrienes are arachidonic ...
more infohttps://pharos.nih.gov/idg/targets/P20292
Involvement of 5-lipoxygenase activating protein in the amyloidotic phenotype of an Alzheimers disease mouse model | Journal...  Involvement of 5-lipoxygenase activating protein in the amyloidotic phenotype of an Alzheimer's disease mouse model | Journal...
... β-site amyloid precursor protein cleaving enzyme 1 or disintegrin and metalloproteinase domain-containing protein 10. By ... MK-591 treatment did not induce any change in the steady-state levels of amyloid-β precursor protein, ... The 5-lipoxygenase enzyme is widely distributed within the central nervous system and its activity is regulated by the presence ... contrast, it resulted in a significant reduction of the γ-secretase complex, at the protein and message level. Furthermore, in ...
more infohttps://jneuroinflammation.biomedcentral.com/articles/10.1186/1742-2094-9-127
ALOX5AP Gene - GeneCards | AL5AP Protein | AL5AP Antibody  ALOX5AP Gene - GeneCards | AL5AP Protein | AL5AP Antibody
Protein Coding), Arachidonate 5-Lipoxygenase Activating Protein, including: function, proteins, disorders, pathways, orthologs ... Membrane-associated proteins in eicosanoid and glutathione metabolism (MAPEG) * Five-lipoxygenase activating protein signature ... Protein details for ALOX5AP Gene (UniProtKB/Swiss-Prot). Protein Symbol:. P20292-AL5AP_HUMAN. Recommended name:. Arachidonate 5 ... Protein Expression for ALOX5AP Gene. See protein expression from ProteomicsDB, MOPED, PaxDb, and MaxQB ...
more infohttps://www.genecards.org/cgi-bin/carddisp.pl?gene=ALOX5AP
Anti-Inflammatory Activity of a Potent, Selective Leukotriene A4 Hydrolase Inhibitor in Comparison with the 5-Lipoxygenase...  Anti-Inflammatory Activity of a Potent, Selective Leukotriene A4 Hydrolase Inhibitor in Comparison with the 5-Lipoxygenase...
LTB4 is able to recruit and activate inflammatory cells, which in turn can cause tissue damage and disease. Elevated levels of ... This relative decrease in potency could partially be ascribed to protein binding because the IC50 value obtained when the ... ABBREVIATIONS: LT, leukotriene; LO, lipoxygenase; FLAP, 5-LO-activating protein; LTA4H, leukotriene A4 hydrolase; JNJ-26993135 ... or 15-lipoxygenase. Lipoxins, such as LXA4, are known to play a role as endogenous anti-inflammatory agents and key mediators ...
more infohttp://jpet.aspetjournals.org/content/321/3/1154
AM-679 (FLAP inhibitor) - Wikipedia  AM-679 (FLAP inhibitor) - Wikipedia
This protein is involved in the production of cysteinyl leukotrienes which are involved in inflammation, and AM-679 has anti- ... Part 2: 3-{5-((S)-1-Acetyl-2,3-dihydro-1H-indol-2-ylmethoxy)-3-tert-butylsulfanyl-1-[4-(5-methoxy-pyrimidin-2-yl)-benzyl]-1H- ... Musiyenko, A.; Correa, L.; Stock, N.; Hutchinson, J. H.; Lorrain, D. S.; Bain, G.; Evans, J. F.; Barik, S. (2009). "A Novel 5- ... Lipoxygenase-Activating Protein Inhibitor, AM679, Reduces Inflammation in the Respiratory Syncytial Virus-Infected Mouse Eye". ...
more infohttps://en.wikipedia.org/wiki/AM-679_(FLAP_inhibitor)
B-Cell Activating Factor (BAFF) Inhibitors - Pipeline Insights, 2017  B-Cell Activating Factor (BAFF) Inhibitors - Pipeline Insights, 2017
B-Cell Activating Factor (BAFF) Inhibitors Phase I and IND Filed Products. Comparative Analysis. B-Cell Activating Factor (BAFF ... B-Cell Activating Factor (BAFF) Inhibitors Filed and Phase III Products. Comparative Analysis. B-Cell Activating Factor (BAFF) ... B-Cell Activating Factor (BAFF) Inhibitors Assessment by Stage and Route of Administration. B-Cell Activating Factor (BAFF) ... B-Cell Activating Factor (BAFF) Inhibitors Assessment by Stage and Molecule Type. B-Cell Activating Factor (BAFF) Inhibitors ...
more infohttps://www.researchandmarkets.com/reports/4036909/b-cell-activating-factor-baff-inhibitors
Compound Report Card  Compound Report Card
Protein-tyrosine phosphatase 1C Homo sapiens 0.237 Show More. Calculated Compound Parent Properties. Mol. Weight. Mol. Weight ... Hematopoietic cell protein-tyrosine phosphatase 70Z-PEP Homo sapiens 0.265 CHEMBL5979 Alkaline phosphatase, tissue-nonspecific ... The two tables below display ChEMBL single-protein targets which are predicted to interact with CHEMBL898. A 1uM and 10 uM cut- ...
more infohttps://www.ebi.ac.uk/chembl/compound/inspect/CHEMBL898
LOX-DB - LipOXygenases DataBase - Literature  LOX-DB - LipOXygenases DataBase - Literature
Because the MK-886-binding protein seems to play a part in activating this enzyme in cells, it is termed the five-lipoxygenase ... A membrane protein with a high affinity for MK-886 and possibly representing the cellular target for MK-886 has been isolated ... Here, we report the isolation of a complementary DNA clone encoding the MK-886-binding protein. We also demonstrate that the ... Recently a compound, MK-886, has been described that blocks the synthesis of leukotrienes in intact activated leukocytes, but ...
more infohttp://www.glycosciences.de/spec/lox-db/show-literature.php?lit_id=197
IUCr) Acta Crystallographica Section F Volume 63, Part 12, December 2007  IUCr) Acta Crystallographica Section F Volume 63, Part 12, December 2007
... thermophilus leads to robust crystallization of the protein in space group P41212; crystals of these mutant proteins show X-ray ... The crystal structure of the minimized α/β-hydrolase fold protein encoded by the gene TTHA1544 from T. thermophilus HB8 has ... In this study, the Korean pine (Pinus koraiensis) vicilin-type 7S seed storage protein was isolated from defatted pine-nut ... HA3, a 70 kDa haemagglutinating protein, is a precursor form of HA3a and HA3b, the subcomponents of Clostridium botulinum type ...
more infohttp://journals.iucr.org/f/issues/2007/12/00/
Recent Advances on 5‐Lipoxygenase Biochemistry  Recent Advances on 5Lipoxygenase Biochemistry
Lipoxygenase (5‐LOX) catalyses two steps in thebiosynthesis of leukotrienes (LTs), lipid mediators of inflammation derived from ... lipoxygenaseactivating protein homodimer in human neutrophils: evidence for a role in leukotriene biosynthesis. Biochemical ... Lipoxygenaseactivating protein stimulates the utilization of arachidonic acid by 5lipoxygenase. European Journal of ... Lipoxygenaseactivating protein inhibitors for inflammatory diseases. Trends in Pharmacological Sciences 29: 72-78. ...
more infohttp://www.els.net/WileyCDA/ElsArticle/refId-a0024630.html
  • Incubation of adipose tissue with 5-LO products resulted in NF-κB activation and augmented secretion of proinflammatory adipokines such as MCP-1, IL-6, and TNF-α. (jimmunol.org)
  • 5‐LOX products are involved in inflammation, allergic reactions, development of cardiovascular disease as well as certain types of cancer. (els.net)
  • 2008) The role of diacylglyceride generation by phospholipase D and phosphatidic acid phosphatase in the activation of 5lipoxygenase in polymorphonuclear leukocytes. (els.net)
  • Scuderi et al (2012) Palmitoylethanolamide exerts neuroprotective effects in mixed neuroglial cultures and organotypic hippocampal slices via peroxisome proliferator-activated receptor-α. (tocris.com)
  • Across all diseases, we identified a large number of further signals (including 58 loci with single-point P values between 10 -5 and 5 × 10 -7 ) likely to yield additional susceptibility loci. (nature.com)
  • Cellular 5‐LOX activity is regulated in a complex manner and depends on cellular localisation, phosphorylation, the intracellular calcium concentration and the redox status of the cell. (els.net)
  • Regulation of cellular 5‐LOX activity. (els.net)
  • Also, possible effects of 5‐LOX products in relation to tumorigenesis have been described. (els.net)
  • Protein Cell. (harvard.edu)
  • 5‐LOX resides as soluble protein in the nucleoplasm or the cytsol, depending on the cell type and/or the phosphorylation status at Ser 271 or Ser 523 . (els.net)
  • Ca 2+ ‐induced formation of 5‐H(P)ETE and LTA 4 by 5‐LOX in presence of scaffold factors CLP (stoichiometry 1:1) and/or phosphatidylcholine ( PC , 25 µg ml −1 ). (els.net)
  • Blue, 5‐LOX catalytic domain. (els.net)