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.
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.
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.
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.
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.
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.- .
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.
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)
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.
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.
Scaffolding proteins that play an important role in the localization and activation of 5-LIPOXYGENASE.
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.
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)
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.
Eighteen-carbon essential fatty acids that contain two double bonds.
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.
Phospholipases that hydrolyze one of the acyl groups of phosphoglycerides or glycerophosphatidates.
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).
Phospholipases that hydrolyze the acyl group attached to the 2-position of PHOSPHOGLYCERIDES.
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).
(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)
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.
Enzyme complexes that catalyze the formation of PROSTAGLANDINS from the appropriate unsaturated FATTY ACIDS, molecular OXYGEN, and a reduced acceptor.
20-carbon saturated monocarboxylic acids.
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)
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)
Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation.
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).
(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.
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.
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.
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.
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.
Liquid chromatographic techniques which feature high inlet pressures, high sensitivity, and high speed.
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.
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.
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)
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.
A class of enzymes that catalyze the hydrolysis of phosphoglycerides or glycerophosphatidates. EC 3.1.-.
FATTY ACIDS in which the carbon chain contains one or more double or triple carbon-carbon bonds.
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.
The rate dynamics in chemical or physical systems.
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.
Long chain organic acid molecules that must be obtained from the diet. Examples are LINOLEIC ACIDS and LINOLENIC ACIDS.
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).
A group of FLAVONOIDS characterized with a 4-ketone.
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.
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.
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.
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.
Eighteen-carbon essential fatty acids that contain three double bonds.
A constitutively-expressed subtype of prostaglandin-endoperoxide synthase. It plays an important role in many cellular processes.
White blood cells. These include granular leukocytes (BASOPHILS; EOSINOPHILS; and NEUTROPHILS) as well as non-granular leukocytes (LYMPHOCYTES and MONOCYTES).
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.
An annual legume. The SEEDS of this plant are edible and used to produce a variety of SOY FOODS.
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.
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)
An enzyme formed from PROTHROMBIN that converts FIBRINOGEN to FIBRIN.
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.
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.
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.
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.
A microanalytical technique combining mass spectrometry and gas chromatography for the qualitative as well as quantitative determinations of compounds.
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.
Intracellular fluid from the cytoplasm after removal of ORGANELLES and other insoluble cytoplasmic components.
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.
A class of drugs designed to prevent leukotriene synthesis or activity by blocking binding at the receptor level.
Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.
Derivatives of PHOSPHATIDYLCHOLINES obtained by their partial hydrolysis which removes one of the fatty acid moieties.
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.
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.
An enzyme found predominantly in platelet microsomes. It catalyzes the conversion of PGG(2) and PGH(2) (prostaglandin endoperoxides) to thromboxane A2. EC
Enzymes that catalyze reversibly the formation of an epoxide or arene oxide from a glycol or aromatic diol, respectively.
The process of converting an acid into an alkyl or aryl derivative. Most frequently the process consists of the reaction of an acid with an alcohol in the presence of a trace of mineral acid as catalyst or the reaction of an acyl chloride with an alcohol. Esterification can also be accomplished by enzymatic processes.
The physiologically active and stable hydrolysis product of EPOPROSTENOL. Found in nearly all mammalian tissue.
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.
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.
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.
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)
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).
A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.
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).
An antineoplastic agent that inhibits DNA synthesis through the inhibition of ribonucleoside diphosphate reductase.
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.
A group of fatty acids that contain 18 carbon atoms and a double bond at the omega 9 carbon.
Oxidases that specifically introduce DIOXYGEN-derived oxygen atoms into a variety of organic molecules.
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.
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.
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)
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.
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.
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)
A group of 1,2-benzenediols that contain the general formula R-C6H5O2.
Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.
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.
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.
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.
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.)
Established cell cultures that have the potential to propagate indefinitely.
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.
A phorbol ester found in CROTON OIL with very effective tumor promoting activity. It stimulates the synthesis of both DNA and RNA.
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)
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)
A non-steroidal anti-inflammatory agent with antipyretic and antigranulation activities. It also inhibits prostaglandin biosynthesis.
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.
A group of 16-carbon fatty acids that contain no double bonds.
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)
The addition of an organic acid radical into a molecule.
A nonsteroidal anti-inflammatory agent with analgesic properties used in the therapy of rheumatism and arthritis.
A sarcoma derived from deep fibrous tissue, characterized by bundles of immature proliferating fibroblasts with variable collagen formation, which tends to invade locally and metastasize by the bloodstream. (Stedman, 25th ed)
Compounds based on benzeneacetamide, that are similar in structure to ACETANILIDES.
Enzymes that catalyze the formation of acyl-CoA derivatives. EC 6.2.1.
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.
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
C22-unsaturated fatty acids found predominantly in FISH OILS.
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.
The salts or esters of salicylic acids, or salicylate esters of an organic acid. Some of these have analgesic, antipyretic, and anti-inflammatory activities by inhibiting prostaglandin synthesis.
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.
Cyclohexane ring substituted by one or more ketones in any position.
Organic compounds containing both the hydroxyl and carboxyl radicals.
An ethylmercury-sulfidobenzoate that has been used as a preservative in VACCINES; ANTIVENINS; and OINTMENTS. It was formerly used as a topical antiseptic. It degrades to ethylmercury and thiosalicylate.
The relationship between the dose of an administered drug and the response of the organism to the drug.
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.
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.
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.
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.
Physiological processes in biosynthesis (anabolism) and degradation (catabolism) of LIPIDS.
Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.
Unstable isotopes of carbon that decay or disintegrate emitting radiation. C atoms with atomic weights 10, 11, and 14-16 are radioactive carbon isotopes.
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.
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.
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)
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.
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.
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.
Elements of limited time intervals, contributing to particular results or situations.
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.
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.
Dioxygenases that catalyze the peroxidation of methylene-interrupted UNSATURATED FATTY ACIDS.
An analytical method used in determining the identity of a chemical based on its mass using mass analyzers/mass spectrometers.
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.
Compounds that inhibit the action of prostaglandins.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis.
Enzymes from the transferase class that catalyze the transfer of acyl groups from donor to acceptor, forming either esters or amides. (From Enzyme Nomenclature 1992) EC 2.3.
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.
Any of various animals that constitute the family Suidae and comprise stout-bodied, short-legged omnivorous mammals with thick skin, usually covered with coarse bristles, a rather long mobile snout, and small tail. Included are the genera Babyrousa, Phacochoerus (wart hogs), and Sus, the latter containing the domestic pig (see SUS SCROFA).
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.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
Peroxidase catalyzed oxidation of lipids using hydrogen peroxide as an electron acceptor.
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.
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)
A plant species of the genus SOLANUM, family SOLANACEAE. The starchy roots are used as food. SOLANINE is found in green parts.
Transport proteins that carry specific substances in the blood or across cell membranes.
(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.
Benzene rings which contain two ketone moieties in any position. They can be substituted in any position except at the ketone groups.
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.
Proteins prepared by recombinant DNA technology.
A class of lipoproteins of small size (18-25 nm) and light (1.019-1.063 g/ml) particles with a core composed mainly of CHOLESTEROL ESTERS and smaller amounts of TRIGLYCERIDES. The surface monolayer consists mostly of PHOSPHOLIPIDS, a single copy of APOLIPOPROTEIN B-100, and free cholesterol molecules. The main LDL function is to transport cholesterol and cholesterol esters to extrahepatic tissues.
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)
Mononuclear phagocytes derived from bone marrow precursors but resident in the peritoneum.
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.
Derivatives of ACETIC ACID. Included under this heading are a broad variety of acid forms, salts, esters, and amides that contain the carboxymethane structure.
Phospholipids which have an alcohol moiety in ethereal linkage with a saturated or unsaturated aliphatic alcohol. They are usually derivatives of phosphoglycerols or phosphatidates. The other two alcohol groups of the glycerol backbone are usually in ester linkage. These compounds are widely distributed in animal tissues.
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.
Highly reactive molecules with an unsatisfied electron valence pair. Free radicals are produced in both normal and pathological processes. They are proven or suspected agents of tissue damage in a wide variety of circumstances including radiation, damage from environment chemicals, and aging. Natural and pharmacological prevention of free radical damage is being actively investigated.
A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by a hydrogen. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. The compound is an inhibitor of HIV replication, acting as a chain-terminator of viral DNA by binding to reverse transcriptase. Its principal side effect is nephrotoxicity. In vivo, dideoxyadenosine is rapidly metabolized to DIDANOSINE (ddI) by enzymatic deamination; ddI is then converted to dideoxyinosine monophosphate and ultimately to dideoxyadenosine triphosphate, the putative active metabolite.
A layer of epithelium that lines the heart, blood vessels (ENDOTHELIUM, VASCULAR), lymph vessels (ENDOTHELIUM, LYMPHATIC), and the serous cavities of the body.
Compounds that bind to and inhibit the action of 5-LIPOXYGENASE-ACTIVATING PROTEINS.
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.
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.
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)
A phenothiazine with actions similar to CHLORPROMAZINE. It is used as an antipsychotic and an antiemetic.
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.
A group of alicyclic hydrocarbons with the general formula R-C5H9.
Derivatives of phosphatidic acid in which the hydrophobic regions are composed of two fatty acids and a polar alcohol is joined to the C-3 position of glycerol through a phosphodiester bond. They are named according to their polar head groups, such as phosphatidylcholine and phosphatidylethanolamine.
A flavoprotein enzyme that catalyzes the univalent reduction of OXYGEN using NADPH as an electron donor to create SUPEROXIDE ANION. The enzyme is dependent on a variety of CYTOCHROMES. Defects in the production of superoxide ions by enzymes such as NADPH oxidase result in GRANULOMATOUS DISEASE, CHRONIC.
Proteins, usually acting in oxidation-reduction reactions, containing iron but no porphyrin groups. (Lehninger, Principles of Biochemistry, 1993, pG-10)
A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function.
A strong oxidizing agent used in aqueous solution as a ripening agent, bleach, and topical anti-infective. It is relatively unstable and solutions deteriorate over time unless stabilized by the addition of acetanilide or similar organic materials.
The space enclosed by the peritoneum. It is divided into two portions, the greater sac and the lesser sac or omental bursa, which lies behind the STOMACH. The two sacs are connected by the foramen of Winslow, or epiploic foramen.
The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.
The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.
GLYCEROL esterified with FATTY ACIDS.
Derivatives of phosphatidic acids in which the phosphoric acid is bound in ester linkage to a serine moiety. Complete hydrolysis yields 1 mole of glycerol, phosphoric acid and serine and 2 moles of fatty acids.
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.
Fatty acid esters of cholesterol which constitute about two-thirds of the cholesterol in the plasma. The accumulation of cholesterol esters in the arterial intima is a characteristic feature of atherosclerosis.
The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.
A common saturated fatty acid found in fats and waxes including olive oil, palm oil, and body lipids.
An element with atomic symbol O, atomic number 8, and atomic weight [15.99903; 15.99977]. It is the most abundant element on earth and essential for respiration.
Granulated cells that are found in almost all tissues, most abundantly in the skin and the gastrointestinal tract. Like the BASOPHILS, mast cells contain large amounts of HISTAMINE and HEPARIN. Unlike basophils, mast cells normally remain in the tissues and do not circulate in the blood. Mast cells, derived from the bone marrow stem cells, are regulated by the STEM CELL FACTOR.
Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.
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.
The process of cleaving a chemical compound by the addition of a molecule of water.
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.
Components of a cell produced by various separation techniques which, though they disrupt the delicate anatomy of a cell, preserve the structure and physiology of its functioning constituents for biochemical and ultrastructural analysis. (From Alberts et al., Molecular Biology of the Cell, 2d ed, p163)

Reactive oxygen intermediate-dependent NF-kappaB activation by interleukin-1beta requires 5-lipoxygenase or NADPH oxidase activity. (1/691)

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)

Interaction of 5-lipoxygenase with cellular proteins. (2/691)

5-Lipoxygenase (5LO) plays a pivotal role in cellular leukotriene synthesis. To identify proteins interacting with human 5LO, we used a two-hybrid approach to screen a human lung cDNA library. From a total of 1.5 x 10(7) yeast transformants, nine independent clones representing three different proteins were isolated and found to specifically interact with 5LO. Four 1.7- to 1.8-kb clones represented a 16-kDa protein named coactosin-like protein for its significant homology with coactosin, a protein found to be associated with actin in Dictyostelium discoideum. Coactosin-like protein thus may provide a link between 5LO and the cytoskeleton. Two other yeast clones of 1.5 kb encoded transforming growth factor (TGF) type beta receptor-I-associated protein 1 partial cDNA. TGF type beta receptor-I-associated protein 1 recently has been reported to associate with the activated form of the TGF beta receptor I and may be involved in the TGF beta-induced up-regulation of 5LO expression and activity observed in HL-60 and Mono Mac 6 cells. Finally, three identical 2.1-kb clones contained the partial cDNA of a human protein with high homology to a hypothetical helicase K12H4. 8 from Caenorhabditis elegans and consequently was named DeltaK12H4. 8 homologue. Analysis of the predicted amino acid sequence revealed the presence of a RNase III motif and a double-stranded RNA binding domain, indicative of a protein of nuclear origin. The identification of these 5LO-interacting proteins provides additional approaches to studies of the cellular functions of 5LO.  (+info)

Leukotriene binding, signaling, and analysis of HIV coreceptor function in mouse and human leukotriene B4 receptor-transfected cells. (3/691)

The mouse leukotriene B4 receptor (m-BLTR) gene was cloned. Membrane fractions of human embryonic kidney 293 cells stably expressing m-BLTR demonstrated a high affinity and specific binding for leukotriene B4 (LTB4, Kd = 0.24 +/- 0.03 nM). In competition binding experiments, LTB4 was the most potent competitor (Ki = 0.23 +/- 0.05 nM) followed by 20-hydroxy-LTB4 (Ki = 1.1 +/- 0.2 nM) and by 6-trans-12-epi-LTB4 and LTD4 (Ki > 1 microM). In stably transfected Chinese hamster ovary cells, LTB4 inhibited forskolin-activated cAMP production and induced an increase of intracellular calcium, suggesting that this receptor is coupled to Gi- and Go-like proteins. In Xenopus laevis melanophores transiently expressing m-BLTR, LTB4 induced the aggregation of pigment granules, confirming the inhibition of cAMP production induced by LTB4. BLT receptors share significant sequence homology with chemokine receptors (CCR5 and CXCR4) that act as human immunodeficiency virus (HIV) coreceptors. However, among the 16 HIV/SIV strains tested, the human BLT receptor did not act as a coreceptor for virus entry into CD4-expressing cells based on infection and cell-cell fusion assays. In 5-lipoxygenase-deficient mice, the absence of leukotriene B4 biosynthesis did not detectably alter m-BLT receptor binding in membranes obtained from glycogen-elicited neutrophils. Isolation of the m-BLTR gene will form the basis of future experiments to elucidate the selective role of LTB4, as opposed to cysteinyl-leukotrienes, in murine models of inflammation.  (+info)

Pneumococcus activation of the 5-lipoxygenase pathway and production of glycoproteins in the middle ear of rats. (4/691)

Pneumococcal otitis media is associated with the production of potent inflammatory mediators (leukotrienes), but the mechanism by which pneumococcus induces production of leukotrienes in the middle ear is poorly understood. In this study, up-regulation of 2 genes that govern the lipoxygenase pathway, cPLA2 and 5-LOX, was observed in rats following inoculation of pneumococcus into the middle ear cavity. Expression of cPLA2 was low, and 5-LOX gene expression was not detected in control animals. Up-regulation of cPLA2 and 5-LOX in middle ear epithelial cells was accompanied by an increase of high-molecular-weight glycoproteins in middle ear fluid and cells. These findings suggest that pneumococcus activates the lipoxygenase pathway by up-regulating expression of the cPLA2 and 5-LOX genes. This, in turn, may stimulate synthesis and secretion of high-molecular-weight glycoproteins that facilitate production of fluid in the middle ear cleft.  (+info)

Leukotriene A synthase activity of purified mouse skin arachidonate 8-lipoxygenase expressed in Escherichia coli. (5/691)

Mouse skin 8-lipoxygenase was expressed in COS-7 cells by transient transfection of its cDNA in pEF-BOS carrying an elongation factor-1alpha promoter. When crude extract of the transfected COS-7 cells was incubated with arachidonic acid, 8-hydroxy-5,9,11, 14-eicosatetraenoic acid was produced as assessed by reverse- and straight-phase high performance liquid chromatographies. The recombinant enzyme also reacted on alpha-linolenic and docosahexaenoic acids at almost the same rate as that with arachidonic acid. Eicosapentaenoic and gamma-linolenic acids were also oxygenated at 43% and 56% reaction rates of arachidonic acid, respectively. In contrast, linoleic acid was a poor substrate for this enzyme. The 8-lipoxygenase reaction with these fatty acids proceeded almost linearly for 40 min. The 8-lipoxygenase was also expressed in an Escherichia coli system using pQE-32 carrying six histidine residues at N-terminal of the enzyme. The expressed enzyme was purified over 380-fold giving a specific activity of approximately 0.2 micromol/45 min per mg protein by nickel-nitrilotriacetate affinity chromatography. The enzymatic properties of the purified 8-lipoxygenase were essentially the same as those of the enzyme expressed in COS-7 cells. When the purified 8-lipoxygenase was incubated with 5-hydroperoxy-6,8,11, 14-eicosatetraenoic acid, two epimers of 6-trans-leukotriene B4, degradation products of unstable leukotriene A4, were observed upon high performance liquid chromatography. Thus, the 8-lipoxygenase catalyzed synthesis of leukotriene A4 from 5-hydroperoxy fatty acid. Reaction rate of the leukotriene A synthase was approximately 7% of arachidonate 8-lipoxygenation. In contrast to the linear time course of 8-lipoxygenase reaction with arachidonic acid, leukotriene A synthase activity leveled off within 10 min, indicating suicide inactivation.  (+info)

Cytosolic phospholipase A2 is essential for both the immediate and the delayed phases of eicosanoid generation in mouse bone marrow-derived mast cells. (6/691)

We have used mice in which the gene for cytosolic phospholipase A2 (cPLA2) has been disrupted to demonstrate the absolute requirement for cPLA2 in both the immediate and the delayed phases of eicosanoid generation by bone marrow-derived mast cells. For the immediate phase, quantitative analysis of the products of the 5-lipoxygenase pathway showed that gene disruption of cPLA2 prevented the provision of arachidonic acid substrate for biosynthesis of proximal intermediates. By analogy, we conclude that arachidonic acid substrate was also not available to prostaglandin endoperoxide synthase 1 in the immediate phase of prostaglandin (PG) D2 generation. These defects occurred with two distinct stimuli, stem cell factor and IgE/antigen, which were, however, sufficient for signal transduction defined by exocytosis of beta-hexosaminidase. Whereas cPLA2 is essential for immediate eicosanoid generation by providing arachidonic acid, its role in delayed-phase PGD2 generation is more complex and involves the activation-dependent induction of prostaglandin endoperoxide synthase 2 and the supply of arachidonic acid for metabolism to PGD2.  (+info)

Relationship of arachidonic acid metabolizing enzyme expression in epithelial cancer cell lines to the growth effect of selective biochemical inhibitors. (7/691)

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)

Gene expression of 5-lipoxygenase and LTA4 hydrolase in renal tissue of nephrotic syndrome patients. (8/691)

Leukotrienes (LT) of the 5-lipoxygenase pathway constitute a class of potent biological lipid mediators of inflammation implicated in the pathogenesis of different models of experimental glomerulonephritis. The key enzyme, 5-lipoxygenase (5-LO), catalyses oxygenation of arachidonic acid to generate the primary leukotriene LTA4. This LT, in turn, serves as a substrate for either LTA4 hydrolase, to form the potent chemoattractant LTB4, or LTC4 synthase, to produce the powerful vasoconstrictor LTC4. To investigate the potential role of LT in the pathogenesis of human glomerulonephritis with nephrotic syndrome, we examined the gene expression of 5-LO and LTA4 hydrolase in renal tissue of 21 adult patients with nephrotic syndrome and 11 controls. The patients consisted of 11 cases of membranous nephropathy (MN), seven focal and segmental glomerulosclerosis (FSGS), two non-IgA mesangial glomerulonephritis and one minimal change disease. Total RNA purified from renal tissue was reverse transcribed into cDNA and amplified with specific primers in a polymerase chain reaction (RT-PCR). Eight patients' renal tissue, four MN and four FSGS, co-expressed 5-LO and LTA4 hydrolase. In situ hybridization analysis revealed 5-LO expression and distribution limited to the interstitial cells surrounding the peritubular capillaries. Comparative clinical and immunohistological data showed that these eight patients had impaired renal function and interstitial changes that significantly correlated with 5-LO expression. These findings suggest that leukotrienes may play an important role in the pathogenesis of MN and FSGS. These results are also relevant to elucidating the pathophysiologic mechanisms which underlie progression to renal failure in these diseases.  (+info)

References for Abcams Recombinant Human 5 Lipoxygenase protein (ab114310). Please let us know if you have used this product in your publication
Description: Quantitativesandwich ELISA kit for measuring Rat Arachidonate 5-lipoxygenase (Alox5) in samples from serum, plasma, cell culture supernates, tissue homogenates. Now available in a cost efficient pack of 5 plates of 96 wells each, conveniently packed along with the other reagents in 5 separate kits ...
Title: Structural Organization of the Regulatory Domain of Human 5- Lipoxygenase. VOLUME: 6 ISSUE: 2. Author(s):John B. Allard and Thomas G. Brock. Affiliation:6301 MSRB III, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109-0642, USA.. Keywords:5-lipoxygenase, structure, c2 domain, toxin, lipase, protein kinase c, sandwich, plat domain. Abstract: The enzyme 5-lipoxygenase (5-LO) initiates the synthesis of leukotrienes. For this reason, 5-LO activity is important for immune defense, whereas improper regulation contributes to pathogenesis, including chronic inflammation, asthma and atherosclerosis. Like all lipoxygenases, the 5-LO protein consists of two domains, a regulatory domain and a catalytic domain. Naturally, the regulatory domain determines catalytic activity and controls leukotriene synthesis. This domain shares features with classical C2 domains in that it has a β-sandwich structure and binds calcium, nucleotides and phospholipids. However, important ...
We mapped a gene predisposing to myocardial infarction to a locus on chromosome 13q12-13. 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 confers almost two times greater risk of stroke. Another ALOX5AP haplotype is associated with myocardial infarction in individuals from the UK. Stimulated neutrophils from individuals with myocardial infarction produce more leukotriene B4, a key product in the 5-lipoxygenase pathway, than do neutrophils from controls, and this difference is largely attributed to cells from males who carry the at-risk haplotype. We conclude that variants of ALOX5AP are involved in the pathogenesis of both myocardial infarction and stroke by increasing leukotriene production and inflammation in the arterial wall ...
Zileuton is an orally active inhibitor of 5-lipoxygenase, and thus inhibits leukotrienes (LTB4, LTC4, LTD4, and LTE4) formation. Zileuton is used for the maintenance treatment of asthma. Zileuton was introduced in 1996.
Leukotrienes, the biologically active metabolites of arachidonic acid, have been implicated in a variety of inflammatory responses, including asthma, arthritis and psoriasis. Recently a compound, MK-886, has been described that blocks the synthesis of leukotrienes in intact activated leukocytes, but has little or no effect on enzymes involved in leukotriene synthesis, including 5-lipoxygenase, in cell-free systems. A membrane protein with a high affinity for MK-886 and possibly representing the cellular target for MK-886 has been isolated from rat and human leukocytes. Here, we report the isolation of a complementary DNA clone encoding the MK-886-binding protein. We also demonstrate that the expression of both the MK-886-binding protein and 5-lipoxygenase is necessary for leukotriene synthesis in intact cells. Because the MK-886-binding protein seems to play a part in activating this enzyme in cells, it is termed the five-lipoxygenase activating protein (FLAP ...
This report by Pace and colleagues provides new insights into the influence of sex (and sex hormones) on leukotriene synthesis and its inhibition. While the potential of these results to be of clinical relevance is exciting, additional preclinical and clinical studies are needed to define the true clinical impact, which is likely to be complex. For example, Pace et al. focus primarily on inflammatory processes and leukocytes that predominantly generate LTB4. Although a number of inflammatory diseases, including scleroderma lung disease (13), inflammatory bowel disease (6), sickle cell disease (14), and cardiovascular disease (15), are reported to be associated with increased LTB4 levels, there are few, if any, examples in which treatment of these diseases with leukotriene synthesis inhibitors has shown benefit. The diseases in which there is the most information relevant to leukotriene biology are asthma, AERD, and allergic rhinitis, to which cysteinyl leukotrienes are known to contribute. For ...
Recently, we have demonstrated by two different methods that lipoxgenases (LOXs) and 14-3-3 proteins form interactions in barley embryos [Holtman, Roberts, Oppedijk, Testerink, van Zeijl and Wang (2000) FEBS Lett. 474, 48-52]. It was shown by both co-immunoprecipitations and surface-plasmon resonance experiments that 13-LOX, but not 9-LOX, forms interactions with 14-3-3 proteins. In the present report we show that the presence of 13-LOX and 14-3-3 proteins was established in high-molecular-mass complexes. Amounts of 13-LOX and 14-3-3 proteins in high-molecular-mass fractions increased during germination, but were reduced after dephosphorylation of protein extracts or competition with the 14-3-3-binding peptide P-Raf-259, indicating that 13-LOX and 14-3-3 proteins interact in a phosphorylation-dependent manner. Chemicals/CAS: 13-lipoxygenase, EC 1.13.11.-; 14-3-3 Proteins; Lipoxygenase, EC; Tyrosine 3-Monooxygenase, EC ...
15 Lipoxygenase 1小鼠单克隆抗体[3G8](ab119774)可与大鼠, 狗, 人, 猴样本反应并经WB, IHC, ICC/IF实验严格验证。所有产品均提供质保服务,中国75%以上现货。
References for Abcams Recombinant Human 15 Lipoxygenase 1 protein (ab114421). Please let us know if you have used this product in your publication
15 Lipoxygenase 2 Polyclonal antibody Antibody 13073-1-AP has been identified with WB, ELISA. 13073-1-AP detected 67-76 kDa band in A431 cells with 1:500-1:3000 dilution...
Discovery of selective imidazole-based inhibitors of mammalian 15-lipoxygenase: Highly potent against human enzyme within a cellular environment ...
Zileuton is an orally active inhibitor of 5-lipoxygenase, the enzyme that catalyzes the formation of leukotrienes from arachidonic acid. It is indicated for the prophylaxis and chronic treatment of asthma in adults and children 12 years of age and older.
The product (9Z,12Z)-(11S)-11-hydroperoxyoctadeca-9,12-dienoate, is converted, more slowly, into (9Z,11E)-(13R)-13-hydroperoxyoctadeca-9,11-dienoate. The enzyme from the
Complete information for ALOX15 gene (Protein Coding), Arachidonate 15-Lipoxygenase, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
abbr.: diHETE; any of several products resulting from dioxygenation of arachidonate at two sites, normally resulting from lipoxygenase action on hydroxyeicosatetraenoates. (6E,8Z,10E,14Z)‐(5S,12S)‐5,12‐dihydroxyeicosa‐6,8,10,14‐tetraen‐1‐oate (abbr.: 5(S),12(S)‐diHETE) is synthesized in human leukocytes by ... ...
BioVision develops and offers a wide variety of products including assay kits, antibodies, recombinant proteins & enzymes, and other innovative research tools for studying Apoptosis, Metabolism, Cell Proliferation, Cellular Stress, Cell Damage and Repair, Diabetes, Obesity and Metabolic Syndrome, Stem Cell Biology, Gene Regulation, Signal Transduction, etc. BioVisions products are currently being sold in more than 60 countries worldwide.
TY - JOUR. T1 - Cigarette smoking stimulates lipoxygenase but not cyclooxygenase pathway in platelets. AU - Chang, Wen Chang. AU - Fukuda, Shoshi. AU - Tai, Hsin Hsiung. PY - 1983/9/15. Y1 - 1983/9/15. N2 - Male rats were exposed to freshly generated cigarette smoke once daily for 4 to 8 weeks. Inhalation of smoke was verified by elevated level of carboxyhemoglobin. Arachidonate metabolism through lipoxygenase and cyclooxygenase pathways in platelets was determined. Cigarette smoking increased 12-lipoxygenase activity significantly without affecting the cyclooxygenase pathway. In view of platelet-leukocyte interactions and potent chemotactic activity of 12-HETE for aortic smooth muscle cell migration, increased 12-lipoxygenase activity may predispose individuals to atherosclerosis, thromboembolism and emphysema commonly found in smokers.. AB - Male rats were exposed to freshly generated cigarette smoke once daily for 4 to 8 weeks. Inhalation of smoke was verified by elevated level of ...
Leukotrienes (LT) are a group of proinflammatory lipid mediators that are implicated in the pathogenesis and progression of atherosclerosis. Here we report that mRNA levels for the three key proteins in LTB4 biosynthesis, namely 5-lipoxygenase (5-LO), 5-LO-activating protein (FLAP), and LTA4 hydrolase (LTA4H), are significantly increased in human atherosclerotic plaque (n = 72) as compared with healthy controls (n = 6). Neither LTC4 synthase nor any of the LT receptors exhibits significantly increased mRNA levels. Immunohistochemical staining revealed abundant expression of 5-LO, FLAP, and LTA4H protein, colocalizing in macrophages of intimal lesions. Human lesion tissue converts arachidonic acid into significant amounts of LTB4, and a selective, tight-binding LTA4H inhibitor can block this activity. Furthermore, expression of 5-LO and LTA4H, but not FLAP, is increased in patients with recent or ongoing symptoms of plaque instability, and medication with warfarin correlates with increased levels ...
Title: Imbalance Between Leukotriene Synthesis and Catabolism Contributes to the Pathogenesis of Allergic Diseases. VOLUME: 3 ISSUE: 4. Author(s): Masafumi Zaitsu. Affiliation:Department of Pediatrics,Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga City 849-8501, Saga, Japan.. Keywords:Dipeptidases, gamma-glutamyl leukotrienase, stem cell factor, lipopolysaccharide, 5-lipoxygenase. Abstract: Recently, there has been great progress in elucidating the biochemistry of the arachidonic acid (AA) metabolism. The abnormal production of leukotrienes (LTs), due to the unbalanced-regulation of synthesizing and catabolizing enzymes, is probably induced by many bioactive substances, including Th2 cell-derived cytokines. Imbalances in these processes may play an important role in allergic reactions and other inflammatory diseases, thus making them potentially prime therapeutic targets for these diseases. Further studies on the regulation of LT-synthesis and catabolism are therefore required to ...
FLAP antibody, Internal (arachidonate 5-lipoxygenase-activating protein) for IHC-P, WB. Anti-FLAP pAb (GTX89246) is tested in Human samples. 100% Ab-Assurance.
Lipoxygenases play a critical role in the biosynthesis of both proinflammatory and pro-resolving mediators and thus can be critical regulators of their balance. Two key enzymes, 5-LOX and 12/15-LOX, have been studied in this context. Notably, humans express three related forms of this enzyme, 12-LOX, 15-LOX type 1, and 15-LOX type 2, while mice express only one form, which is usually referred to as 12/15-LOX because it catalyzes both 12- and 15-LOX reactions (34). 5-LOX plays a role in the formation of both proinflammatory leukotrienes and pro-resolving lipoxins, and the determination of which product is generated in a given setting is dependent on 5-LOX subcellular localization (34). Nuclear 5-LOX is located near leukotriene A4 (LTA4) hydrolase, which converts the product of 5-LOX, LTA4, to LTB4. In contrast, when 5-LOX is cytoplasmic, LTA4 is converted to lipoxin A4 (LXA4) by cytoplasmic 12/15-LOX. In macrophages, the nuclear localization of 5-LOX is mediated by MAPKAPK2-mediated ...
In the paper entitled Effect of montelukast added to inhaled budesonide on control of mild to moderate asthma by M J Vaquerizo et al which appeared in the March issue of Thorax (2003;58:204-11), there is an error in the first sentence of the abstract which should read Proinflammatory leukotrienes, which are not completely inhibited by inhaled corticosteroids, may contribute to asthmatic problems. The publishers apologise for this error.. ...
Plants continuously have to defend themselves against life threatening events such as drought, mechanical damage, temperature stress and potential pathogens. A main component of the plant defense mechanism is the lipoxygenase pathway. Products of this pathway are involved in wound healing, pest resistance, signaling, or ... read more have antimicrobial and antifungal activity. The first step in the lipoxygenase pathway is the reaction of linoleic or linolenic acids with molecular oxygen, catalyzed by the enzyme lipoxygenase. The formed hydroperoxy fatty acids are highly reactive and dangerous for the plant, and are therefore further metabolized by other enzymes such as allene oxide synthase, hydroperoxide lyase, peroxygenase or divinyl ether synthase. Hydroperoxide lyases are heme-containing enzymes of the cytochrome P450 class (CYP74B). They cleave the C-C bond adjacent to the hydroperoxy group in the lipoxygenase products, resulting in the formation of w-oxo acids and volatile C6- and ...
A1777 is a selective 5-lipoxygenase inhibitor that reduces leukocytes proliferation without affecting the eosinophils of mast cells.
Inflammation in the vascular wall is important for development of atherosclerosis. We have shown previously that arachidonate 15-lipoxygenase type B (ALOX15B) is more highly expressed in human atherosclerotic lesions than in healthy arteries. This en
Oxidative stress is a major brain injury mechanism after ischemic stroke. 12/15-lipoxygenase (12/15-LOX) is a key mediator of oxidative stress, contributing to neuronal cell death and vascular leakage. Nonetheless, the mechanism leading to its upregulation is currently unknown. We show here that Signal Transducers and Activators of Transcription (STATs), specifically STAT6 and possibly STAT1, increase transcription of 12/15-LOX in neuronal cells. Both p-STAT6 and -1 bound to specific STAT binding sites in the mouse 12/15-LOX promoter. Small interfering RNA (siRNA) knockdown showed STAT6 to be the dominant regulator, reducing 12/15-LOX promoter activation and cell death in oxidatively stressed HT22 cells. STAT6 siRNA efficiently prevented the increase of 12/15-LOX in murine primary neurons, both after induction of oxidative stress and after oxygen-glucose deprivation. Early activation of STAT6 and STAT1 in mice was consistent with a role in regulating 12/15-LOX in focal ischemia. Brains of human ...
Fingerprint Dive into the research topics of Enzymatic properties of the 15-lipoxygenase of human cultured keratinocytes. Together they form a unique fingerprint. ...
The incubation of isolated human PMN in vitro results in the rapid accumulation of endogenous adenosine, which has profound inhibitory effects on many cell functions, including LT synthesis. In the present study, we show that when endogenous adenosine is eliminated enzymatically from PMN suspensions, or its actions blocked with receptor antagonists, human PMN respond very strongly to low micromolar concentrations of AA for the synthesis of 5-LO products. This observation contrasts with the widely held perception that resting human PMN respond poorly to exogenous AA for LTB4synthesis and that the measurable synthesis of 5-LO products in the presence of AA requires the simultaneous stimulation with another agonist. Thus, our studies establish clearly that AA can trigger, in the absence of other added PMN stimuli, an important generation of 5-LO products and that the effect of exogenous AA is highly sensitive to the inhibitory effect of adenosine A2a receptor engagement on PMN. Therefore, these ...
We investigated the interaction of human PMNs with human vascular tissue to determine the extent to which cellular activation state was involved in PMN-induced vascular responsiveness. We determined that both unactivated and activated PMNs induced a cell number-dependent vasocontraction in HUV, the nature of which was dependent on the activation state of the cells. The vasoconstrictor response observed for unactivated PMNs was endothelium-independent, was due to soluble factor(s) in the cell supernatant and was partially blocked by an inhibitor of leukotriene biosynthesis. For the activated PMNs, the response was endothelium-dependent, was not due to a soluble factor and was linearly related to their activation state.. One of the most interesting findings of this study was that both unactivated and activated PMNs contracted HUV but that their respective responses were quite different in nature. Treatment of HUV with unactivated PMNs had no significant effect on the response to serotonin, which ...
Dear all, I was hoping someone could help me locate a source for the following antibodies - they are quite urgent and any information on companies selling them would be very welcome. The antibodies are: Phospholipase A2 activating protein Ab. 5-lipoxygenase activating protein 5-lipoxygenase They are required for western blotting. Also any companies (preferably in the UK) which can make them would alos be welcome although those already approached have said it would take 20 weeks to produce these Ab. which is far to long. Thank you all in advance, Gary Morley gmorley at ...
Looking at my sequence of animals, there are a few conclusions I can come to. One conclusion I can come to is that my protein, lipoxygenase, must be very common because a variety of animals are in the sequence you may not think of as relatives. Sense lipoxygenase is involved in the metabolism that shows…
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The invention is directed to the enhanced expression and purification of lipoxygenase enzymes. These enzymes are of wide-spread industrial importance, often produced in heterologous microbial systems. Preferably, the lipoxygenase produced by the methods of the invention is a plant-derived enzyme and expressed at high-levels in a microbial system that includes a protease-deficient host and one or more chaperone expression plasmids. The invention is also directed to amino acid and nucleic acid fragments of the lipoxygenase enzyme including fragments in expression constructs encoding all or a portion of one or more lipoxygenase genes. The invention is also directed to methods of manufacturing bread and other food and also non-food products with lipoxygenase manufactured by the methods of the invention.
N. Topley, R. Steadman, B. Spur, J.D. Williams; Independent Activation of the 5-Lipoxygenase Pathway and Respiratory Burst in Human Polymorphonuclear Leukocytes (PMN) in Response to Phagocytic Stimuli. Clin Sci (Lond) 1 January 1988; 74 (s18): 65P-66P. doi: Download citation file:. ...
Lipid bodies are cellular compartments containing triacylglycerols. They are encompassed by a phospholipid monolayer and decorated with characteristic proteins. In plants, lipid bodies are synthesized during seed formation but acquire new proteins during seed germination. In germinating cucumber (Cucumis sativus) seeds, the set of newly synthesized proteins appearing in the lipid bodies at the early stage of triacylglycerol mobilization comprises a special form of lipoxygenase. We isolated the lipid body lipoxygenase and characterized fragments prepared by limited proteolysis and cleavage with cyanogen bromide. A very early expression of lipid body lipoxygenase was found by studying the rate of de novo synthesis of lipoxygenase forms during germination. This allowed a clear distinction of this enzyme from other lipoxygenase isoforms. Hence, for determining the molecular structure of lipid body lipoxygenase we analyzed a cDNA prepared from mRNA of cotyledons at day 1 of germination. From the cDNA ...
Bermudez, AF, Coles, B, Coffey, M and ODonnell, V (2003) Protein kinase C regulates 15-lipoxygenase oxidation of membrane-bound arachidonate in human monocytes In: 10th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicne, 2003-11-20 - 2003-11-24, SEATTLE, WASHINGTON. Full text not available from this repository ...
Cancer cell metastasis is the single most threatening occurrence of tumor progression and predicts patient prognosis as well as survival. Invasion can be regulated by the Met receptor tyrosine kinase (c-Met), integrin beta4, and the lipid enzyme, 12-Lipoxygenase (12-LOX). Therefore we sought to determine if beta4, c-MET and 12-LOX comprise a signaling axis. c-Met is implicated in cancer cell dissemination through regulation of invasion in EMT where cell-cell junctions are disturbed to allow motility. Furthermore, beta4 promotes cellular adhesion to the extracellular matrix through hemidesmosomes. However, the homeostatic signaling functions of beta4s cytoplasmic tail can be hijacked by growth factor receptors during tumor growth to promote tumor cell survival and metastasis. Beta4 interacts with 12-LOX, an enzyme that metabolizes arachidonic acid to yield 12(S)-HETE, a bioactive lipid that also promotes invasion, tumor growth, and resistance to apoptosis. Our findings reveal that c-Met and beta4
Madeswaran, Arumugam, Muthuswamy Umamaheswari, Kuppuswamy Asokkumar, Thirumalaisamy Sivashanmugam, Varadharajan Subhadradevi, Puliyath Jagannath (2011) Docking studies: In silico lipoxygenase inhibitory activity of some commercially available flavonoids. [Publication] Full text not available from this repository ...
Menard C, Valastro B, Martel M-, Chartier E, Marineau A, Baudry M, et al. AMPA receptor phosphorylation is selectively regulated by constitutive phospholipase A(2) and 5-lipoxygenase activities. Hippocampus. 2005;15(3):370-80. ...
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Ago H, Kanaoka Y, Irikura D, Lam BK, Shimamura T, Austen KF, Miyano M. Crystal structure of a human membrane protein involved in cysteinyl leukotriene biosynthesis. Nature. 2007 Aug 02; 448(7153):609-12 ...
Accepted name: arachidonate 12-lipoxygenase. Reaction: arachidonate + O2 = (5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate. Other name(s): δ12-lipoxygenase; 12-lipoxygenase; 12δ-lipoxygenase; C-12 lipoxygenase; 12S-lipoxygenase; leukotriene A4 synthase; LTA4 synthase. Systematic name: arachidonate:oxygen 12-oxidoreductase. Comments: The product is rapidly reduced to the corresponding 12S-hydroxy compound.. Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 82391-43-3. References:. 1. Hamberg, M. and Samuelsson, B. Prostaglandin endoperoxides. Novel transformations of arachidonic acid in human platelets. Proc. Natl. Acad. Sci. USA 71 (1974) 3400-3404. [PMID: 4215079]. 2. Nugteren, D.H. Arachidonate lipoxygenase in blood platelets. Biochim. Biophys. Acta 380 (1975) 299-307. [PMID: 804329]. 3. Wallach, D.P. and Brown, V.R. A novel preparation of human platelet lipoxygenase. Characteristics and inhibition by a variety of phenyl hydrazones and ...
Lipoxygenases (EC 1.13.11.-) are a family of (non-heme), iron-containing enzymes most of which catalyze the dioxygenation of polyunsaturated fatty acids in lipids containing a cis,cis-1,4- pentadiene into cell signaling agents that serve diverse roles as autocrine signals that regulate the function of their parent cells, paracrine signals that regulate the function of nearby cells, and endocrine signals that regulate the function of distant cells. The lipoxygenases are related to each other based upon their similar genetic structure and dioxygenation activity. However, one lipoxygenase, ALOXE3, while having a lipoxygenase genetic structure, possesses relatively little dioxygenation activity; rather its primary activity appears to be as an isomerase that catalyzes the conversion of hydroperoxy unsaturated fatty acids to their 1,5-epoxide, hydroxyl derivatives. Lipoxygenases are found in eukaryotes (plants, fungi, animals, protists); while the third domain of terrestrial life, the archaea, ...
It is clear that leukotrienes mediate inflammatory response; new aspects of leukotriene function have recently been described. In this study, we demonstrate that leukotrienes are key chemical mediators in the control of parasite burdens in mice infected with Strongyloides venezuelensis. High leukotriene levels were detected in the lungs and small intestines of Swiss mice. In infected Swiss mice treated with MK886, a leukotriene synthesis inhibitor, numbers of adult worms, and eggs/g/feces were greater than in infected-only animals. The MK886 treatment inhibited leukotriene B-4 production in the lungs and small intestines, albeit on different postinfection days. Similarly, parasite burdens and eggs/g/feces were greater in 5-lipoxygenase(-/-) mice than in wild-type animals. These observation were confirmed by histopathological study of the duodena. We subsequently observed significant lower numbers of eosinophils; and mononuclear cells in the blood, peritoneal cavity fluid, and bronchoalveolar ...
Cholesterol metabolism in normal adrenal cortex cells is acutely regulated by ACTH stimulation, rising appreciably within 3 minutes of treatment and peaking within 10-15 minutes (3). Defects in either PKA or G protein coupling, as seen in mutant mouse adrenal cell sub-lines, block this response by preventing cAMP formation (11). Other signaling pathways playing key roles in adrenal responses to ACTH include lipoxygenase activation (12) and, at least in adrenal fasciculata cells, stimulation mediated by receptors for IGF1, retinoids, and thyroid hormone; several cytokines, conversely, can suppress production of steroid hormones by these cells (13). For the most part, I will focus here on the mechanisms of acute adrenal fasciculata responses to cAMP and its analogs, which are generally shared with testicular and ovarian cells. It is interesting to note, however, that StAR regulation in another adrenal steroidogenic cell type, the glomerulosa cell, responds via alternative pathways involving Ca2+ ...
New anti-inflammatory agents possessing dual cyclooxygenase/lipoxygenase (COX/LOX) inhibition were discovered by computer-aided prediction of biological activity for 573 virtually designed chemical compounds. Prediction of biological activity was performed by PASS, and prediction results were analyz …
This work describes the structure of human 5-lipoxygenase (5-LOX) (Gilbert, Bartlett et al. 2011) and the techniques required to ascertain the structure. 5-LOX is a notoriously unstable enzyme with important biological functions. The human 5-LOX has been implicated in many disease states including asthma, atherosclerosis and cancer. Part of 5-LOX biology is the inherent instability of the enzyme, which is thought to help regulate the production of its pro-inflammatory products, the leukotrienes. Our objective was stabilizing the enzyme for in vitro studies without affecting catalytic fidelity. I was able to quantitate stabilizing and destabilizing point mutations of 5-LOX by thermal denaturation and kinetic analysis along with other biochemical techniques. Through rigorous site-directed mutagenesis experiments and multiple expression protocols, I was able to over-express an engineered form of 5-LOX that is soluble and stable for biochemical studies and most importantly amenable to crystallization. Our
Reactive oxygen species (ROS) and the redox state of a cell have been implicated in several signal transduction cascades including those that regulate cell proliferation. Specifically, signaling by several growth factors, including epidermal growth factor (EGF), produces a transient increase in ROS. One effect of increases in ROS is the inactivation of tyrosine phosphatases. Pani et al. found that the redox status of cells in culture was different in sparse and dense cultures (sparse cultures have more ROS than dense cultures) and that this difference correlated with whether the cells exhibited contact inhibition. Dense cultures had lower levels of the active [guanosine triphosphate (GTP)-bound] form of the small GTPase Rac-1. Treatment of sparse cultures with drugs to inhibit leukotriene biosynthesis decreased the levels of ROS to those measured in dense cultures, suggesting that Rac-1 may stimulate leukotriene biosynthesis as a mechanism to increase ROS in sparsely cultured cells. The authors ...
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Leukotrienes (LT) C4, D4, and E4are major contributors to the pathobiology of human bronchial asthma. Therefore, it is likely that compounds that antagonize the action or inhibit the formation of...
Treatment of PBMCs and BEAS-2B with montelukast at concentrations of 10-4M to 10-6M, and with MK-886 at a concentration of 10-4M significantly inhibited release of IL-8 by RV-infected BEAS-2B. RANTES, IL-6 and IP-10 release was inhibited at all concentrations tested by both drugs, while IL-11 release was inhibited only after treatment with montelukast. Treatment of BEAS-2B cells with montelukast or with MK-886 at a concentration of 10-6M inhibited release of all cytokines measured, irrespective of exposure to conditioned media of RV-infected PBMCs, while 10-9M montelukast inhibited the release of IL-8, IL-11 and IL-6, and 10-9M MK-886 suppressed the release of IL-8 and RANTES. ...
Moradian N, Ochs HD, Sedikies C, Hamblin MR, Camargo CA Jr, Martinez JA, Biamonte JD, Abdollahi M, Torres PJ, Nieto JJ, Ogino S, Seymour JF, Abraham A, Cauda V, Gupta S, Ramakrishna S, Sellke FW, Sorooshian A, Wallace Hayes A, Martinez-Urbistondo M, Gupta M, Azadbakht L, Esmaillzadeh A, Kelishadi R, Esteghamati A, Emam-Djomeh Z, Majdzadeh R, Palit P, Badali H, Rao I, Saboury AA, Jagan Mohan Rao L, Ahmadieh H, Montazeri A, Fadini GP, Pauly D, Thomas S, Moosavi-Movahed AA, Aghamohammadi A, Behmanesh M, Rahimi-Movaghar V, Ghavami S, Mehran R, Uddin LQ, Von Herrath M, Mobasher B, Rezaei N. ...
p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.,/p> ,p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.,/p> ,p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).,/p> ,p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x,sup>64,/sup> + x,sup>4,/sup> + x,sup>3,/sup> + x + 1. The algorithm is described in the ISO 3309 standard. ,/p> ,p class=publication>Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.,br /> ,strong>Cyclic redundancy and other checksums,/strong>,br /> ,a href=>Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993),/a>),/p> Checksum:i ...
HZ52 displays anti-inflammatory effectiveness in rats and protects mice against PAF-induced surprise Since many substances that potently inhibited 5-LO in vitro lacked effectiveness in vivo we 1st assessed the effectiveness of HZ52 in animal models linked to LTs thats carrageenan-induced pleurisy in rats and PAF-induced surprise in mice. a crucial part for 5690-03-9 supplier 5-LO items in the severe lethal toxicity of PAF in mice (Chen et al. 1994 Goulet et al. 1994 Byrum et al. 1997 which therefore represents the right model to check the in vivo effectiveness of LT-synthesis inhibitors (Lorrain et al. 2010 Administration of 200 μg·kg?1 PAF to vehicle-treated mice triggered 95% mortality within 30 min hence only 1 away of 20 animals survived. HZ52 in the dosage of 10 mg·kg?1 however not at 1.5 or 5 mg·kg?1 (i.p.) resulted in success of eight 5690-03-9 supplier out of 10 pets (Desk 2). Treatment using the 5-LO inhibitor zileuton in the dose of 10 mg·kg?1 (i.p.) prior to the PAF injection ...
TY - JOUR. T1 - Cys-leukotrienes promote fibrosis in a mouse model of eosinophil-mediated respiratory inflammation. AU - Ochkur, Sergei I.. AU - Protheroe, Cheryl A.. AU - Li, Wen. AU - Colbert, Dana C.. AU - Zellner, Katie R.. AU - Shen, Hua Hao. AU - Luster, Andrew D.. AU - Irvin, Charles G.. AU - Lee, James J.. AU - Lee, Nancy A.. N1 - Copyright: Copyright 2014 Elsevier B.V., All rights reserved.. PY - 2013/12. Y1 - 2013/12. N2 - Leukotrienes (i.e., products of the 5-lipoxygenase pathway) are thought to be contributors to lung pathologies. Moreover, eosinophils have been linked with pulmonary leukotriene activities both as potential sources of these mediators and as responding effector cells. The objective of the present study was to define the role(s) of leukotrienes in the lung pathologies accompanying eosinophil-associated chronic respiratory inflammation. A transgenic mouse model of chronic T helper (Th) 2-driven inflammation expressing IL-5 from T cells and human eotaxin-2 locally in the ...
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Sigma-Aldrich offers abstracts and full-text articles by [Maaike Bruinsma, Sarah van Broekhoven, Erik H Poelman, Maarten A Posthumus, Martin J Müller, Joop J A van Loon, Marcel Dicke].
Gingerforce modulates the 5-lipoxygenase enzyme. Garlicforce by New Chapter Supports stomach, liver, and intestinal health. Garlicforce Supports blood platelet health and cardiovascular function and Promotes healthy inflammation response.
ethyl arachidonate 1808-26-0 NMR spectrum, ethyl arachidonate H-NMR spectral analysis, ethyl arachidonate C-NMR spectral analysis ect.
In humans, the active ingredient hyperforin is also an inhibitor of PTGS1, arachidonate 5-lipoxygenase, SLCO1B1 and an inducer ... It is a medicinal herb with antidepressant activity and anti-inflammatory properties as an arachidonate 5-lipoxygenase ... Arachidonate 5-lipoxygenase ...Specific function: Catalyzes the first step in leukotriene biosynthesis, and thereby plays a ... 2002;325:781-5. Kumar V, Mdzinarishvili A, Kiewert C, Abbruscato T, Bickel U, van der Schyf CJ, Klein J (2006). "NMDA receptor- ...
An antileukotriene is a drug which functions as a leukotriene-related enzyme inhibitor (arachidonate 5-lipoxygenase) or ... "Inhibition of five lipoxygenase activating protein (FLAP) by MK-886 decreases atherosclerosis in apoE/LDLR-double knockout mice ... Arachidonate 5-lipoxygenase ...Specific function: Catalyzes the first step in leukotriene biosynthesis, and thereby plays a ... Examples of 5-LOX inhibitors include drugs, such as meclofenamate sodium and zileuton. Some chemicals found in trace amounts in ...
ALOX12B (i.e. arachidonate 12-lipoxygenase, 12R type) forms R chirality products, i.e. 12R-HpETE and 12R-HETE. Similarly, ... The enzymes 15-lipoxygenase-1 (15-LO-1 or ALOX15) and 15-lipoxygenase-2 (15-LO-2, ALOX15B) metabolize arachidonic acid to the S ... Other reactions of lipoxygenases generate cellular damage; murine models implicate 15-lipoxygenase in the pathogenesis of ... The enzyme arachidonate 12-lipoxygenase (12-LO or ALOX12) metabolizes arachidonic acid to the S stereoisomer of 12- ...
InChI=1S/C17H14Cl2F2N2O3/c18-11-6-22-7-12(19)15(11)23-16(24)10-3-4-13(26-17(20)21)14(5-10)25-8-9-1-2-9/h3-7,9,17H,1-2,8H2,(H,22 ... 38 (5): 847-56. doi:10.1111/j.1365-2222.2008.02950.x. ISSN 1365-2222. PMID 18307529.. ...
InChI=1S/C22H30N2O2/c1-26-22(20-10-6-3-7-11-20)18-24-16-14-23(15-17-24)13-12-21(25)19-8-4-2-5-9-19/h2-11,21-22,25H,12-18H2,1H3 ...
108 (5): 671-80. doi:10.1067/mai.2001.119555. PMID 11692087.. *^ Deree J, Martins JO, Melbostad H, Loomis WH, Coimbra R (2008 ... 1985 May;180(5):398-401. *^ Essayan DM (2001). "Cyclic nucleotide phosphodiesterases". J Allergy Clin Immunol. ... InChI=1S/C7H8N4O2/c1-10-5-4(8-3-9-5)6(12)11(2)7(10)13/h3H,1-2H3,(H,8,9) Y ... 5][6] Seizures can also occur in severe cases of toxicity, and are considered to be a neurological emergency.[7] Its toxicity ...
2-[(1S, 2S, 4R, 8S, 9S,11S, 12S, 13R)-6-cyclohexyl-11-hydroxy-9, 13-dimethyl-16-oxo-5, 7-dioxapentacyclo [,9.04, 8.013 ... 5-11,15-17H2,1-4H3/t22-,23-,24-,26+,27+,29+,30-,31-,32+/m0/s1 Y ... Arachidonate 5-lipoxygenase inhibitors. *Zileuton. Thromboxane ...
5] In 2016, it was the 62nd most prescribed medication in the United States, with more than 12 million prescriptions.[6] ...
5] In the United Kingdom a dose costs the NHS about 0.86 pounds as of 2019.[1] In 2016 it was the 95th most prescribed ...
Available in oral and injectable form, theophylline is a long-acting bronchodilator that prevents asthma episodes. It belongs to the chemical class methyl xanthines (along with caffeine). It is prescribed in severe cases of asthma or those that are difficult to control. It must be taken 1-4 times daily, and doses cannot be missed. Blood tests are required to monitor therapy and to indicate when dosage adjustment is necessary. Side effects can include nausea, vomiting, diarrhea, stomach or headache, rapid or irregular heart beat, muscle cramps, nervous or jittery feelings, and hyperactivity. These symptoms may signal the need for an adjustment in medication. It may promote acid reflux, also known as GERD, by relaxing the lower esophageal sphincter muscle. Some medications, such as seizure and ulcer medications and antibiotics containing erythromycin, can interfere with the way theophylline works. Coffee, tea, colas, cigarette-smoking, and viral illnesses can all affect the action of theophylline ...
The 5% preparation for patient use is an adherent beige paste,[3][8] and it is also available in some countries as a tablet ... InChI=1S/C16H14N2O4/c1-7(2)8-3-4-12-9(5-8)13(19)10-6-11(16(20)21)14(17)18-15(10)22-12/h3-7H,1-2H3,(H2,17,18)(H,20,21) Y ... 7. Synthesis of Antiallergic 5-Oxo-5H-\1]benzopyrano\2,3-b]pyridines". Journal of Medicinal Chemistry. 28 (5): 559-68. doi: ... A 2011 review found a one-week supply of amlexanox 5% paste to cost $30.[6] ...
InChI=1S/C8H10N4O2/c1-2-3-12-6-5(9-4-10-6)7(13)11-8(12)14/h4H,2-3H2,1H3,(H,9,10)(H,11,13,14) Y ...
5] In 2016 it was the 166th most prescribed medication in the United States with more than 3 million prescriptions.[6] ...
Retrieved 5 December 2015.. [permanent dead link] *^ Hamilton, Richart (2015). Tarascon Pocket Pharmacopoeia 2015 Deluxe Lab- ... InChI=1S/C20H30NO3.BrH/c1-14(2)21(3)16-9-10-17(21)12-18(11-16)24-20(23)19(13-22)15-7-5-4-6-8-15;/h4-8,14,16-19,22H,9-13H2,1-3H3 ... 5] In the United States, a month worth of medication costs 100 to 200 USD.[6] ...
978-0-89281-498-5. .. *^ Woskresensky A (1842). "Über das Theobromin". Liebigs Annalen der Chemie und Pharmacie. 41: 125-127. ... 108 (5): 671-80. doi:10.1067/mai.2001.119555. PMID 11692087.. *^ "3,7-Dimethylxanthine (Theobromine)". Toxnet, US National ... 978-3-642-13442-5. . PMID 20859797.. *^ Baer, Donald M.; Elsie M. Pinkston (1997). Environment and Behavior. Westview Press. p ... Theobromine was first discovered in 1841[5] in cacao beans by Russian chemist Aleksandr Voskresensky.[6] Synthesis of ...
In children 6 to 14 years of age the usual dosage is one 5 mg chewable tablet a day. The dose is preferably taken in the ... The Mont in Montelukast stands for Montreal, the place where Merck (MSD) developed the drug.[5] ... Montelukast is administered as montelukast sodium, with 5.2 mg of montelukast sodium being equivalent to 5 mg of montelukast.[8 ...
1R,2S)-rel-8-Hydroxy-5-[1-hydroxy-2-(isopropylamino)butyl]-quinolin-2(1H)-one ... Yoshizaki, Shiro; Manabe, Yoshiaki; Tamada, Shigeharu; Nakagawa, Kazuyuki; Tei, Seiso (1977). "Isomers of erythro-5-(1-hydroxy- ...
43 (5): 604-15. doi:10.1093/ageing/afu096. PMID 25038833.. *^ Andre, L; Gallini, A; Montastruc, F; Montastruc, JL; Piau, A; ... 978-0-7817-8763-5. .. *^ Barash, Paul G. (2009). Clinical Anesthesia. ISBN 9780781787635. . Archived from the original on 20 ... 312 (2): 780-5. doi:10.1124/jpet.104.075093. PMID 15356218.. *^ Lee, Jun-Ho; Shin, Eun-Joo; Jeong, Sang Min; Kim, Jong-Hoon; ... 5]; anticholinergic agents do not antagonize the binding at nicotinic acetylcholine receptors at the neuromuscular junction, ...
5/h10-11,13,16,19-21,31H,6-9,12,14-15H2,1-5H3/t16-,19-,20-,21-,25-,26-,27-,28-/m0/s1 Y ...
Arachidonate 5-lipoxygenase has been identified as playing a significant role in the survival of prostate cancer cells. ... In particular, arachidonate 5-lipoxygenase inhibitors produce massive, rapid programmed cell death in prostate cancer cells. ... Ghosh J, Myers CE (October 1998). "Inhibition of arachidonate 5-lipoxygenase triggers massive apoptosis in human prostate ... The 5-year survival rate in the United States is 99%. Globally it is the second most common type of cancer and the fifth ...
... s are synthesized in the cell from arachidonic acid by arachidonate 5-lipoxygenase. The catalytic mechanism involves ... The lipoxygenase pathway is active in leukocytes and other immunocompetent cells, including mast cells, eosinophils, ... by the enzyme arachidonate 5-lipoxygenase. Leukotrienes use lipid signaling to convey information to either the cell producing ... 5-HETE can be further metabolized to 5-oxo-ETE and 5-oxo-15-hydroxy-ETE, all of which have pro-inflammatory actions similar but ...
The isorinic acid derivative perovskoate may also contribute to an anti-inflammatory effect as an arachidonate 5-lipoxygenase ... They are generally 3-5 cm long (1.2-2.0-inch) and 0.8-2 cm wide (0.3-0.8-inch), although narrower in some populations. The ... 4-5. Missouri Botanical Garden (b). Missouri Botanical Garden (c). Missouri Botanical Garden (d). Hedge 1990, p. 221. Keys & ... 2, 5. Proctor 1999, p. 107. Burrell 2002, p. 53. Mani 1978, p. 113. Curtis's Botanical Magazine 1912. Tareen & Qadir 1991, p. ...
Hussey HJ, Tisdale MJ (1996). "Inhibition of tumour growth by lipoxygenase inhibitors". Br. J. Cancer. 74 (5): 683-687. doi: ... Ghosh J, Myers CE (1998). "Inhibition of arachidonate 5-lipoxygenase triggers massive apoptosis in human prostate cancer cells ... Ding XZ, Iversen P, Cluck MW, Knezetic JA, Adrian TE (1999). "Lipoxygenase inhibitors abolish proliferation of human pancreatic ... mediates the survival-promoting effects of arachidonate 5-lipoxygenase in prostate cancer cells". Cancer Lett. 336 (1): 185-95 ...
The primary product of the lipoxygenase, 15-HPETE is believed to react with the enzyme further to produce the 14,15-epoxide, ... Arachidonate 5-lipoxygenase Arachidonate 15-lipoxygenase Leukotriene 15-Hydroxyicosatetraenoic acid Greene ER, Huang S, Serhan ... Claesson HE (September 2009). "On the biosynthesis and biological role of eoxins and 15-lipoxygenase-1 in airway inflammation ... Forsell PK, Brunnström A, Johannesson M, Claesson HE (2012). "Metabolism of anandamide into eoxamides by 15-lipoxygenase-1 and ...
When acting on GLA, Arachidonate 5-lipoxygenase produces no leukotrienes and the conversion by the enzyme of arachidonic acid ... 16 (5): 279-282. Archived from the original (PDF) on 2014-01-12. Nasaruddin, Mohd hanif; Noor, Noor Qhairul Izzreen Mohd; Mamat ... 57 (5 Suppl): 732S-736S; discussion 736S-737S. PMID 8386433. King, Michael W. "Introduction to the Eicosanoids". The Medical ... doi:10.1007/s11248-011-9543-5. PMID 21853296. Flider, Frank J (May 2005). "GLA: Uses and New Sources" (PDF). INFORM. ...
... and the arachidonate 5-lipoxygenase enzyme. Factors that limit the bioactivity of curcumin or its analogs include chemical ... 59 (5): 1671-1690. doi:10.1021/acs.jmedchem.5b01009. ISSN 0022-2623. PMC 4791574 . PMID 26505758. Reuter, S.; Gupta, S. C.; ... 60 (5): 1620-1637. doi:10.1021/acs.jmedchem.6b00975. PMC 5346970 . PMID 28074653. Vogel, H.; Pelletier, J. (1815). "Curcumin - ... The first mechanism involves a chain extension reaction by cinnamic acid and 5 malonyl-CoA molecules that eventually arylized ...
First, human eosinophils use Arachidonate 15-lipoxygenase-1 (or possibly Arachidonate 15-lipoxygenase-2 to metabolize 5-oxo-ETE ... Second, human platelets use 12-lipoxygenase to metabolize 5-oxo-ETE to 5-oxo-12(S)-hydroperxy-eicosatetraenoat which is rapidly ... and lipoxygenase-derived eicosanoids". Drug Metabolism and Disposition. 39 (2): 180-90. doi:10.1124/dmd.110.035121. PMC 3033693 ... oxygenation of this arachidonic acid with by activated arachidonate 5-lipoxygenase (ALOX5) to form 5(S)-hydroperoxy-6E,8Z,11Z, ...
Arachidonate 5-lipoxygenase has been identified as playing a significant role in the survival of prostate cancer cells.[186][ ... "Inhibition of arachidonate 5-lipoxygenase triggers massive apoptosis in human prostate cancer cells". Proc. Natl. Acad. Sci. U. ... arachidonate 5-lipoxygenase inhibitors produce massive, rapid programmed cell death in prostate cancer cells.[186][187][188] ... 2 (5): 389-96. doi:10.1038/nrc801. PMC 4124639 . PMID 12044015.. *^ Scott WW, Johnson DE, Schmidt JE, Gibbons RP, Prout GR, ...
108 (5): 671-80. doi:10.1067/mai.2001.119555. PMID 11692087.. *^ Marques LJ, Zheng L, Poulakis N, Guzman J, Costabel U ( ... 5] In August 2011, a report, based on NASA studies with meteorites found on Earth, was published suggesting xanthine and ... InChI=1S/C5H4N4O2/c10-4-2-3(7-1-6-2)8-5(11)9-4/h1H,(H3,6,7,8,9,10,11) Y ...
... , also known as ALOX5, 5-lipoxygenase, 5-LOX, or 5-LO, is a non-heme iron-containing enzyme (EC 1.13 ... "Alox5 - arachidonate 5-lipoxygenase". WikiGenes.. *^ Fahel JS, de Souza MB, Gomes MT, Corsetti PP, Carvalho NB, Marinho FA, de ... arachidonate 5-lipoxygenase activity. • dioxygenase activity. • metal ion binding. • protein binding. • oxidoreductase activity ... lipoxygenase pathway. • neutrophil degranulation. • cytokine-mediated signaling pathway. • interleukin-18-mediated signaling ...
Kuhn, Hartmut; Walther, Matthias; Kuban, Ralf Jürgen (2002). "Mammalian arachidonate 15-lipoxygenases". Prostaglandins & Other ... 12-lipoxygenase, and 15-lipoxygenase-2, and selected metabolites of the latter lipoxygenases show no such association.[66][67][ ... 15-Lipoxygenase 1[edit]. 15-lipoxygenase 1 (ALOX15), while best known for converting the 20 carbon polyunsaturated fatty acid, ... 15-lipoxygenase 2[edit]. 15-lipoxygenase type 2 (ALOX15B) strongly prefers arachidonic acid over linoleic acid and in ...
Arachidonate 5-lipoxygenase. *LTA4 hydrolase (B4 synthesis). *LTC4 synthase ... Enzymatic conversion into 5,6-dihydroxy-7,9,11,14-eicosatetraenoic acid by mouse liver cytosolic epoxide hydrolase". J. Biol. ... 5,6-epoxyicosa-7,9,11,14-tetraenoate hydrolase. Other names in common use include LTA4 hydrolase, LTA4H, and leukotriene A4 ...
Bryant, R.W., Bailey, J.M., Schewqe, T. and Rapoport, S.M. (1982). „Positional specificity of a reticulocyte lipoxygenase. ... B enzm: 1.1/2/3/4/5/6/7/8/10/11/13/14/15-18, 2.1/2/3/4/5/6/7/8, 2.7.10, 2.7.11-12, 3.1/2/3/4/5/6/7,, 3.4.21/22/23/24, ... Oliw, E.H. & Sprecher, H. (1989). „Metabolism of polyunsaturated fatty acids by an (n-6)-lipoxygenase associated with human ... Narumiya, S. & Salmon, J.A. (1982). „Arachidonic acid-15-lipoxygenase from rabbit peritoneal polymorphonuclear leukocytes". ...
Brash A. R., Boeglin W. E., Chang M. S. (Jun 1997)։ «Discovery of a second 15S-lipoxygenase in humans»։ Proc Natl Acad Sci U S ... Arachidonate. Ավանդական անվանում. (5Z,8Z,11Z,14Z)-Icosa-5,8,11,14-tetraenoic acid[1]. ... Zhu D, Ran Y (May 2012)։ «Role of 15-lipoxygenase/15-hydroxyeicosatetraenoic acid in hypoxia-induced pulmonary hypertension»։ J ... A neglected platelet-derived 12-lipoxygenase product»։ J Chromatogr B 964: 26-40։ PMID 24685839։ doi:10.1016/j.jchromb.2014.03. ...
Other lipoxygenases-8-LO, 12-LO and 15-LO-make other eicosanoid-like products. To act, 5-LO uses the nuclear-membrane enzyme 5- ... Phinney, SD; RS Odin; SB Johnson & RT Holman (March 1, 1990). "Reduced arachidonate in serum phospholipids and cholesteryl ... Lipoxygenase oxidation removes no C=C double bonds, and leads to the LK. After oxidation, the eicosanoids are further modified ... DGLA and EPA compete with AA for access to the cyclooxygenase and lipoxygenase enzymes. So the presence of DGLA and EPA in ...
Antileukotrines are anti-inflammatory agents which function as leukotriene-related enzyme inhibitors (arachidonate 5- ... lipoxygenase) or leukotriene receptor antagonists (cysteinyl leukotriene receptors) and consequently oppose the function of ... 75 (5): 407-413. doi:10.1139/y97-077. PMID 9250374.. *^ Dery, R.E.; Mathison, R.; Davison, J.; Befus; A.D. (2001). "Inhibition ... 42 (5): 305-14. doi:10.1081/JAS-62950. PMID 16036405.. *^ K S Broughton; Johnson, CS; Pace, BK; Liebman, M; Kleppinger, KM ( ...
If arachidonate is acted upon by a lipoxygenase instead of cyclooxygenase, Hydroxyeicosatetraenoic acids and leukotrienes are ... The prostaglandins are synthesized in the cell membrane by the cleavage of arachidonate from the phospholipids that make up the ... The arachidonate is then acted upon by the cyclooxygenase component of prostaglandin synthase. This forms a cyclopentane ring ... Each beta oxidative cut of the acyl-CoA molecule yields 5 ATP molecules. The acetyl-CoA produced by beta oxidation enters the ...
Arachidonate lipoxygenase 3. Arachidonate 12-lipoxygenase, 12R type Epidermolytic hyperkeratosis (bullous ichthyosis, bCIE) ... 층판상 어린선, type 5 606545 ALOXE3 Arachidonate lipoxygenase 3 Autosomal Recessive Congenital Ichthyosis 615023 CERS3 ceramide ... Serine peptidase inhibitor, Kazal type 5 Neutral lipid storage disease with ichthyosis 275630 ABHD5 1-acylglycerol-3-phosphate ...
Arachidonate 5-lipoxygenase. *Atrophin 1. *BH3 interacting-domain death agonist. *BRAF (gene) ...
The enzymes 15-lipoxygenase-1 (ALOX15 and 15-lipoxygenase-2 (ALOX15B metabolize arachidonic acid to 15- ... The enzyme 12-lipoxygenase (ALOX12) metabolizes arachidonic acid to 12-hydroperoxyeicosatetraenoic acid (12-HPETE) which may ... Zhu, D; Ran, Y (May 2012). "Role of 15-lipoxygenase/15-hydroxyeicosatetraenoic acid in hypoxia-induced pulmonary hypertension ... A neglected platelet-derived 12-lipoxygenase product". J Chromatogr B. 964: 26-40. doi:10.1016/j.jchromb.2014.03.015. PMID ...
NeuroReport 12:53-57, 2001 Bazan NG, Birkle DL, Reddy TS: Docosahexaenoic acid (22:6, n 3) is metabolized to lipoxygenase ... Brain Res 100:99-110, 1975 Aveldano MI, Bazan NG: Rapid production of diacylglycerols enriched in arachidonate and stearate ... Eur J Biochem 145:21-29, 1984 Birkle DL, Bazan NG: Lipoxygenase and cyclooxygenase reaction products and incorporation into ... is metabolized to lipoxygenase reaction products in the retina. Biochem Biophys Res Comm 125:741-747, 1984 Beuckmann CT, Gordon ...
Arachidonate-5-Lipoxygenase (ALOX5) Antibody from Abbexa 20-abx102802 , [100 ug: < span>328.00 EUR] [1 mg: < span>815.00 EUR] [ ... Rat Arachidonate 5-lipoxygenase (Alox5) ELISA kit from Cusabio 1-CSB-E16982r , [1 plate of 96 wells: < span>900.00 EUR] [10 ... Arachidonate 5-Lipoxygenase (ALOX5) Antibody from Abbexa 20-abx001770 , [100 ul: < span>411.00 EUR] [200 ul: < span>592.00 EUR ... Arachidonate-5-Lipoxygenase (ALOX5) Antibody from Abbexa 20-abx102800 , [100 ug: < span>425.00 EUR] [10 ug: < span>133.00 EUR ...
Arachidonate 5-lipoxygenase, also known as ALOX5, 5-lipoxygenase, 5-LOX, or 5-LO, is a non-heme iron-containing enzyme (EC 1.13 ... "Alox5 - arachidonate 5-lipoxygenase". WikiGenes.. *^ Fahel JS, de Souza MB, Gomes MT, Corsetti PP, Carvalho NB, Marinho FA, de ... arachidonate 5-lipoxygenase activity. • dioxygenase activity. • metal ion binding. • protein binding. • oxidoreductase activity ... lipoxygenase pathway. • neutrophil degranulation. • cytokine-mediated signaling pathway. • interleukin-18-mediated signaling ...
Lipoxygenase inhibitors at the US National Library of Medicine Medical Subject Headings (MeSH) MeSH list of agents 82016859. ... Arachidonate 5-lipoxygenase inhibitors are compounds that slow or stop the action of the arachidonate 5-lipoxygenase (5- ... lipoxygenase or 5-LOX) enzyme, which is responsible for the production of inflammatory leukotrienes. The overproduction of ... Arachidonate 5-lipoxygenase ...Specific function: Catalyzes the first step in leukotriene biosynthesis, and thereby plays a ...
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OXER1, a G protein-coupled oxoeicosatetraenoid receptor, mediates the survival-promoting effects of arachidonate 5-lipoxygenase ... OXER1, a G protein-coupled oxoeicosatetraenoid receptor, mediates the survival-promoting effects of arachidonate 5-lipoxygenase ... OXER1, a G protein-coupled oxoeicosatetraenoid receptor, mediates the survival-promoting effects of arachidonate 5-lipoxygenase ... OXER1, a G protein-coupled oxoeicosatetraenoid receptor, mediates the survival-promoting effects of arachidonate 5-lipoxygenase ...
Recombinant Protein and Arachidonate 5-lipoxygenase Antibody at MyBioSource. Custom ELISA Kit, Recombinant Protein and Antibody ... Arachidonate 5-lipoxygenase. Arachidonate 5-lipoxygenase ELISA Kit. Arachidonate 5-lipoxygenase Recombinant. Arachidonate 5- ... lipoxygenase Antibody. Also known as Arachidonate 5-lipoxygenase (5-LO) (5-lipoxygenase).. Catalyzes the first step in ... Below are the list of possible Arachidonate 5-lipoxygenase products. If you cannot find the target and/or product is not ...
Arachidonate 5-Lipoxygenase, Arachidonic Acid 5-Lipoxygen, item number: L2623-10C.100 from United States Biological at Biomol! ... Anti-Lipoxygenase, 5- (5-LOX, 5-LO, 5-LPG, Arachidonate 5-Lipoxygenase, Arachidonic Acid 5-Lipoxygen ... Product information "Anti-Lipoxygenase, 5- (5-LOX, 5-LO, 5-LPG, Arachidonate 5-Lipoxygenase, Arachidonic Acid 5-Lipoxygen" ... Customer review for "Anti-Lipoxygenase, 5- (5-LOX, 5-LO, 5-LPG, Arachidonate 5-Lipoxygenase, Arachidonic Acid 5-Lipoxygen" ...
THE 5-LOX interface involving the four cysteines 159, 300, 416 and 418 is important for the translocation to the nuclear ... Lipoxin and resolvin biosynthesis is dependent on 5-lipoxygenase activating protein.. 26159646. 2015. Variants in the ... Inhibitors of its function impede translocation of 5-lipoxygenase from the cytoplasm to the cell membrane and inhibit 5- ... lipoxygenase activation. Alternatively spliced transcript variants encoding different isoforms have been identified for this ...
Arachidonate 5-Lipoxygenase) ELISA Kit OSCAR DIAGNOSTIC SERVICES PVT. an India based Company in Delhi. ... Arachidonate 5-Lipoxygenase) ELISA Kit. Rabbit 5-LO (Arachidonate 5-Lipoxygenase) ELISA Kit. ... Arachidonate 5-Lipoxygenase) ELISA Kit » Rabbit 5-LO (Arachidonate 5-Lipoxygenase) ELISA Kit. Rabbit 5-LO (Arachidonate 5- ... Lipoxygenase) ELISA Kit. Rabbit 5-LO (Arachidonate 5-Lipoxygenase) ELISA Kit. Rabbit 5-LO (Arachidonate 5-Lipoxygenase) ELISA ...
Arachidonate 5-Lipoxygenase (Alox5) Inhibition. Evidences showed that neutrophil-derived leukotriene support breast cancer ... Pharmacologic inhibition of arachidonate 5-lipoxyenase (Alox5) by zileuton (203) could inhibit the pro-metastatic activity of ... Zileuton: the first 5-lipoxygenase inhibitor for the treatment of asthma. Ann Pharmacother. (1996) 30:858-64. doi: 10.1177/ ... 5. Borregaard N. Neutrophils, from marrow to microbes. Immunity. (2010) 33:657-70. doi: 10.1016/j.immuni.2010.11.011 ...
... Jagadananda Ghosh*. Departments of ... Central role of arachidonate 5-lipoxygenase in the regulation of cell growth and apoptosis in human prostate cancer cells. Adv ... Inhibition of arachidonate 5-lipoxygenase triggers massive apoptosis in human prostate cancer cells. Proc. Natl. Acad. Sci. USA ... Cite this article as: Ghosh J. Arachidonate-5-Lipoxygenase (ALOX5): A Master Regulator for Prostate Cancer Cell Survival. Clin ...
Compare 5-Lipoxygenase ELISA Kits from leading suppliers on Biocompare. View specifications, prices, citations, reviews, and ... Alox5, Arachidonate 5-lipoxygenase (Alox5). *. Detection Range: 0.156 ng/mL-10 ng/mL ... 5-Lipoxygenase ELISA Kits. The ELISA (enzyme-linked immunosorbent assay) is a widely used application for detecting and ... Select up to 5 products from below to compare or request more information. * ...
Arachidonate 5-Lipoxygenase Activating Protein, including: function, proteins, disorders, pathways, orthologs, and expression. ... Lipoxygenases (LOXs) are a family of non-heme iron dioxygenases that are involved in the production and metabolism of fatty ... arachidonate 5-lipoxygenase activating protein,expressed in cells of myeloid origin,localized in the nuclear envelop,involved ... There are six lipoxygenase isozymes; 5-LOX, 12R-LOX, 12S-LOX, 15-LOX-1, 15-LOX-2 and E-LOX. ...
InChI=1S/C17H14Cl2F2N2O3/c18-11-6-22-7-12(19)15(11)23-16(24)10-3-4-13(26-17(20)21)14(5-10)25-8-9-1-2-9/h3-7,9,17H,1-2,8H2,(H,22 ... 38 (5): 847-56. doi:10.1111/j.1365-2222.2008.02950.x. ISSN 1365-2222. PMID 18307529.. ...
Arachidonate 12-lipoxygenase, 12R-type. Mus musculus (Mouse). Loading... O75342 Arachidonate 12-lipoxygenase, 12R-type. Homo ... Manganese lipoxygenase. Magnaporthe oryzae (strain 70-15 / ATCC MYA-4617 / FGSC 8958) (Rice blast fungus). Loading... ... Arachidonate 12-lipoxygenase, epidermal-type. Rattus norvegicus (Rat). Loading... F1LQ70 Arachidonate 12-lipoxygenase, 12S-type ...
Arachidonate 5-lipoxygenase inhibitor Arachidonate 5-lipoxygenase PubMed PubMed PubMed Cyclooxygenase inhibitor Cyclooxygenase ... InChI=1S/C7H7NO3/c8-4-1-2-6(9)5(3-4)7(10)11/h1-3,9H,8H2,(H,1 ... Download InChI ...
Arachidonate 15-lipoxygenase. MGLYRIRVSTGASLYAGSNNQVQLWLVGQHGEAALGKRLWPARGKETELK.... unknown. Arachidonate 5-lipoxygenase. ... Resveratrol (3,5,4-trihydroxystilbene) is a polyphenolic phytoalexin. It is a stilbenoid, a derivate of stilbene, and is ... InChI=1S/C14H12O3/c15-12-5-3-10(4-6-12)1-2-11-7-13(16)9-14(17)8-11/h1-9,15-17H/b2-1+. ... E)-5-(2-(4-hydroxyphenyl)ethenyl)-1,3-benzenediol(E)-5-(2-(4-hydroxyphenyl)ethenyl)-1,3-benzenediol ...
Hsieh M-S, Yu S-C, Hsueh Y-M, Chiu W-T, Lee H-M. Gene Variants of Arachidonate 5-lipoxygenase-activating protein (ALOX5AP) And ... Hsieh, M-S, Yu, S-C, Hsueh, Y-M, Chiu, W-T & Lee, H-M 2008, Gene Variants of Arachidonate 5-lipoxygenase-activating protein ( ... Hsieh, M-S., Yu, S-C., Hsueh, Y-M., Chiu, W-T., & Lee, H-M. (2008). Gene Variants of Arachidonate 5-lipoxygenase-activating ... Gene Variants of Arachidonate 5-lipoxygenase-activating protein (ALOX5AP) And Risks of Ischemic Stroke in The Taiwanese ...
5):844-852. doi: 10.1093/rheumatology/kew499. Clinical Trial; Clinical Trial, Phase III; Comparative Study; Multicenter Study; ... The arachidonate 5-lipoxygenase activating protein gene polymorphism is associated with the risk of scleroderma-related ... The arachidonate 5-lipoxygenase activating protein (ALOX5AP) regulates synthesis of leukotrienes (LTs), which are important ... Kowal-Bielecka O1, Chwiesko-Minarowska S2, Bernatowicz PL2, Allanore Y3, Radstake T4,5, Matucci-Cerinic M6, Broen J5, ...
Nonredox-type 5-lipoxygenase (5-LO) inhibitors such as ZM230487 or L-739.010 potently suppress leukotriene biosynthesis at low ... Here, we show that inhibition of 5-LO product formation by nonredox-type 5-LO inhibitors in human isolated polymorphonuclear ... Arachidonate 5-Lipoxygenase / metabolism * Arsenites / pharmacology * Benzeneacetamides* * Bridged Bicyclo Compounds / ... Thus, compared with 5-LO product synthesis induced by the Ca2+-mobilizing agent ionophore A23187, cell stress-induced 5-LO ...
Conversely, alternative activation resulted in the up-regulation of the M2 marker arachidonate 15-lipoxygenase and unexpectedly ... Differential regulation of arachidonate metabolism-related enzymes in human macrophage differentiation and polarization. A, ... as well as the arachidonate 5-lipoxygenase (ALOX5), and leukotriene A4 hydrolase. As expected, classical activation was ... arachidonate 5-lipoxygenase; COX, cyclooxygenase; Mo, monocyte; Mφ, macrophage. ...
arachidonate 5-lipoxygenase. MGI:87999 Go Annotations as Summary Text (Tabular View) (GO Graph). Automated description from the ... Orthologous to human ALOX5 (arachidonate 5-lipoxygenase).. Go Annotations in Tabular Form (Text View) (GO Graph) Filter ... Predicted to have arachidonate 5-lipoxygenase activity and iron ion binding activity. Involved in leukotriene biosynthetic ...
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arachidonate 5-lipoxygenase. MGI:87999 5 matching records from 5 references.. Summary by Age and Assay: Numbers in the table ...
Arachidonate 5-Lipoxygenase / physiology* * Aspirin / adverse effects* * Asthma / chemically induced* * Asthma / drug therapy ... The pivotal role of 5-lipoxygenase products in the reaction of aspirin-sensitive asthmatics to aspirin Am Rev Respir Dis. 1993 ... We examined the effects of an inhibitor of 5-lipoxygenase, zileuton, in a group of eight asthmatic patients with known ...
101914238 ALOX5; arachidonate 5-lipoxygenase 101917252 LTA4H; leukotriene A4 hydrolase 101917253 leukotriene C4 synthase-like ... arachidonate 5-lipoxygenase [EC:] K01254 LTA4H; leukotriene-A4 hydrolase [EC:] K00807 LTC4S; leukotriene-C4 ... 101910798 GGT5; gamma-glutamyltransferase 5 101910629 GGT1; gamma-glutamyltransferase 1 101911072 GPX2; glutathione peroxidase ... 5; gamma-glutamyltranspeptidase / glutathione hydrolase / leukotriene-C4 hydrolase [EC:] K00432 gpx ...
Rabbit polyclonal 5 Lipoxygenase (phospho S271) antibody validated for WB, ELISA, IHC and tested in Human. Immunogen ... Arachidonate 5-lipoxygenase antibody. *arachidonic 5-lipoxygenase alpha-10 isoform antibody. *arachidonic 5-lipoxygenase delta- ... Belongs to the lipoxygenase family.. Contains 1 lipoxygenase domain.. Contains 1 PLAT domain. ... All lanes : Anti-5 Lipoxygenase (phospho S271) antibody (ab59395) at 1/500 dilution. Lane 1 : Extracts from HuvEc cells.. Lane ...
Rabbit polyclonal 5 Lipoxygenase antibody validated for WB, ELISA, IHC and tested in Human and Mouse. Referenced in 2 ... Arachidonate 5-lipoxygenase antibody. *arachidonic 5-lipoxygenase alpha-10 isoform antibody. *arachidonic 5-lipoxygenase delta- ... Belongs to the lipoxygenase family.. Contains 1 lipoxygenase domain.. Contains 1 PLAT domain. ... All lanes : Anti-5 Lipoxygenase antibody (ab59341) at 1/500 dilution. Lane 1 : Extracts from HuvEc cells without immunizing ...
  • Arachidonate 5-lipoxygenase , also known as ALOX5 , 5-lipoxygenase , 5-LOX , or 5-LO , is a non- heme iron-containing enzyme (EC that in humans is encoded by the ALOX5 gene . (
  • The ALOX5 gene, which occupies 71.9 kilo base 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. (
  • ALOX5 products, particularly 5-hydroxyeicosatetraenoic acid and 5-oxo-eicosatetraenoic acid , promote the proliferation of these ALOX5 aberrantly expressing tumor cell lines suggesting that ALOX5 acts as a pro-malignancy factor for them and by extension their parent tumors. (
  • Required for leukotriene biosynthesis by ALOX5 (5-lipoxygenase). (
  • Ghosh J. Arachidonate-5-Lipoxygenase (ALOX5): A Master Regulator for Prostate Cancer Cell Survival. (
  • Orthologous to human ALOX5 (arachidonate 5-lipoxygenase). (
  • ALOX5 (ENST00000374391.7) at chr10:45374216-45446117 - Homo sapiens arachidonate 5-lipoxygenase (ALOX5), transcript variant 5, mRNA. (
  • from RefSeq NM_001320862) ALOX5 (ENST00000622021.4) at chr10_GL383546v1_alt:215007-286950 - Homo sapiens arachidonate 5-lipoxygenase (ALOX5), transcript variant 3, mRNA. (
  • from RefSeq NM_001256154) ALOX5 (ENST00000612635.4) at chr10:45374280-45445687 - arachidonate 5-lipoxygenase (from HGNC ALOX5) ALOX5 (ENST00000542434.5) at chr10:45374176-45446119 - Homo sapiens arachidonate 5-lipoxygenase (ALOX5), transcript variant 3, mRNA. (
  • HM592258 - Homo sapiens arachidonic 5-lipoxygenase (ALOX5) mRNA, complete cds, alternatively spliced. (
  • HM592259 - Homo sapiens arachidonic 5-lipoxygenase delta-13 isoform (ALOX5) mRNA, complete cds, alternatively spliced. (
  • HM592261 - Homo sapiens arachidonic 5-lipoxygenase delta-p10 isoform (ALOX5) mRNA, complete cds, alternatively spliced. (
  • JQ728550 - Homo sapiens LOX-5 splice variant (ALOX5) mRNA, complete cds, alternatively spliced. (
  • The mouse 5-LO gene, ALOX5 , has been shown to contribute to the development of atherosclerosis [ 2 ]. (
  • ALOX5AP (Arachidonate 5-Lipoxygenase Activating Protein) is a Protein Coding gene. (
  • The arachidonate 5-lipoxygenase activating protein (ALOX5AP) regulates synthesis of leukotrienes (LTs), which are important mediators of inflammation and connective tissue remodelling. (
  • from RefSeq NR_137328) ALOX5AP (ENST00000380490.4) at chr13:30735508-30764426 - Homo sapiens arachidonate 5-lipoxygenase activating protein (ALOX5AP), transcript variant 1, mRNA. (
  • from RefSeq NM_001629) ALOX5AP (ENST00000617770.4) at chr13:30713478-30764425 - Homo sapiens arachidonate 5-lipoxygenase activating protein (ALOX5AP), transcript variant 2, mRNA. (
  • from RefSeq NM_001204406) ALOX5AP (ENST00000479597.1) at chr13:30742336-30744396 - arachidonate 5-lipoxygenase activating protein (from HGNC ALOX5AP) LTC4S (ENST00000639087.2) at chr5_KV575244v1_fix:559563-562224 - Homo sapiens leukotriene C4 synthase (LTC4S), mRNA. (
  • MG134610 - Synthetic construct Xenopus tropicalis clone IMAGE:6999522 arachidonate 5-lipoxygenase activating protein (alox5ap) gene, encodes complete protein. (
  • The M1 macrophages exhibited preferential induction of arachidonate 5-lipoxygenase activating protein (ALOX5AP), whereas M2 macrophages had a high-level expression of arachidonate 15-lipoxygenase (ALOX15). (
  • Genetic variation in the arachidonate 5-lipoxygenase-activating protein (ALOX5AP) is associated with myocardial infarction in the German population. (
  • Genetic variation in the genes ALOX5AP (arachidonate 5-lipoxygenase-activating protein) and LTA4H (leukotriene A4 hydrolase) has previously been shown to contribute to the risk of MI (myocardial infarction) and stroke in Icelandic and Scottish populations. (
  • FLAP (5-lipoxygenase activating protein), encoded by the ALOX5AP gene, likely acts as an arachidonic acid-binding and transfer protein to facilitate 5LO activity [ 4 ]. (
  • Single SNPs and haplotypes of ALOX5AP have been associated with myocardial infarction in multiple populations [ 5 - 7 ]. (
  • Inhibition of 5-Lox induces apoptosis in prostate cancer cells by inactivating PKCε which is prevented by 5-oxoETE, and activators of PKCε prevent 5-Lox inhibition-induced apoptosis, suggesting that 5-Lox metabolites exert survival signaling via PKCε. (
  • Interestingly, we found that U73122, an inhibitor of PLC-beta, interrupts the apoptosis-preventing effect of 5-oxoETE, and exogenous diacyl-glycerol effectively prevents 5-Lox inhibition-induced apoptosis, suggesting that 5-oxoETE signals via OXER1 to promote prostate cancer cell survival. (
  • Effect of 5-Lox inhibition on prostate cancer cell survival. (
  • Surprisingly, it was found that inhibition of 5-lipoxygenase does not inhibit Akt or ERKs which are known for their roles in cell survival. (
  • Here, we show that inhibition of 5-LO product formation by nonredox-type 5-LO inhibitors in human isolated polymorphonuclear leukocytes (PMNL) depends on the activation pathway of 5-LO. (
  • Thus, compared with 5-LO product synthesis induced by the Ca2+-mobilizing agent ionophore A23187, cell stress-induced 5-LO product formation involving 5-LO kinase pathways required ~10- to 100-fold higher concentrations of ZM230487 or L-739.010 for comparable 5-LO inhibition. (
  • Experiments using purified 5-LO revealed that Ca2+ is no prerequisite for potent enzyme inhibition by ZM230487, and exposure of PMNL to the combination of ionophore and cell stress did not restore potent 5-LO suppression. (
  • Selective inhibition of arachidonate 5-lipoxygenase by novel acetohydroxamic acids III. (
  • Selective inhibition of arachidonate 5-lipoxygenase by novel acetohydroxamic acids: I. Biochemical assessment in vitro and ex vivo Br. (
  • Inhibition of 5-lo Activating Protein (Flap) Activity Decreases Proteinuria in Streptozotocin(Stz)-induced Diabetic Rats. (
  • Inhibition of arachidonate 5-lipoxygenase triggers prostate cancer cell death through rapid activation of c-Jun N-terminal kinase. (
  • Several botanicals, including Spanish needles ( Bidens pilosa ) [ 4 , 5 ] and cinnamon extract ( Cinnamomum cassia )[ 6 ] have been reported to have significant effects upon a number of allergic processes, including but not limited to the inhibition of histamine release and synthesis of lipid-derived mediators. (
  • Arachidonate 5-lipoxygenase inhibitors are compounds that slow or stop the action of the arachidonate 5-lipoxygenase (5-lipoxygenase or 5-LOX) enzyme, which is responsible for the production of inflammatory leukotrienes. (
  • The enzyme 5-lipoxygenase (5-LO) plays a key role in regulating the production of leukotrienes. (
  • The phospho-specific antibody to Ser523 on 5-LO is thus likely to provide a valuable tool for studies of the role of 5-LO regulation in diseases such as asthma, fibrosis and atherosclerosis.The enzyme 5-lipoxygenase (5-LO) plays a key role in regulating the production of leukotrienes (LTs) (Funk, 2001). (
  • Both leukotrienes and the hydroxyeicosatetraenoids (HETEs) are products of 5-lipoxygenase activity. (
  • For example, pulmonary tissues synthesize the peptido-leukotrienes (LTC 4 , D 4 and E 4 ), which are products of 5-lipoxygenase, in response to immunological challenge. (
  • Inflammatory mediators, leukotrienes, are generated from arachidonic acid (polyunsaturated n -6 fatty acid) by the enzyme 5-lipoxygenase. (
  • 5‐Lipoxygenase (5‐LOX) catalyses two steps in the biosynthesis of leukotrienes (LTs), lipid mediators of inflammation derived from arachidonic acid. (
  • 5‐LOX produces 5‐HPETE, leukotrienes and together with other dioxygenases lipoxins. (
  • Lipoxygenase (LOX) enzyme transforms linoleic, arachidonic and other polyunsaturated fatty acids into biologically active metabolites implicated in the inflammation-related and immunological reactions like hydroperoxy fatty acids and leukotrienes [ 6 ]. (
  • LY293111 was also known to have inhibitory effects on 5-lipoxygenase, which is upstream of the production of leukotrienes. (
  • Zileuton is a specific inhibitor of 5-lipoxygenase and thus inhibits leukotriene (LTB4, LTC4, LTD4, and LTE4) formation. (
  • Also inhibits arachidonate 5-lipoxygenase (IC 50 = 16 nM). (
  • Cyclic adenosine 3',5'-monophosphate inhibits the availability of arachidonate to prostaglandin synthetase in human platelet suspensions. (
  • Fuscoside: an anti-inflammatory marine natural product which selectively inhibits 5-lipoxygenase. (
  • Human 12-lipoxygenase (encoded by ALOX12 ) and 15-lipoxygenase (encoded by ALOX15 ) have been localized to atherosclerotic plaques, suggesting that 12/15LO activity is involved in the development of atherosclerosis [ 8 - 10 ]. (
  • One notable example of an important role of eicosanoids in cancer is the regulation of cancer cell survival by a group of arachidonic acid metabolites which are generated via the 5-lipoxygenase pathway. (
  • The 5‐lipoxygenase pathway is part of the innate immune system. (
  • Genes of the 5-lipoxygenase pathway are compelling candidates for atherosclerosis. (
  • Further, lipoxygenase pathway SNPs that were associated with measures of atherosclerosis were associated with markers of inflammation (CRP, ICAM-1) and calcification (MGP). (
  • These results suggest that variants in lipoxygenase pathway genes may have pleiotropic effects on multiple components that determine risk of cardiovascular disease. (
  • The current research was motivated by the role of lipoxygenase pathway gene products in inflammation, initiation/progression of atherosclerosis, and their modulation of expression by glucose. (
  • Separate lines of research have identified the 5-lipoxygenase/leukotriene B 4 receptor pathway and the PPAR pathway as potential targets for prevention or treatment of this disease. (
  • The third pathway for metabolizing arachidonic acid, the lipoxygenase pathway catalyzes the incorporation of one oxygen molecule into polyunsaturated fatty acids to yield a 1-hydroperoxy-2, 4-trans, cis-pentadiene product [ 14 - 16 ]. (
  • Higgs G.A. (1989) Novel 5-Lipoxygenase Inhibitors in Inflammation and Asthma. (
  • Since atherosclerosis involves arterial inflammation, a polymorphism in the 5-lipoxygenase gene promoter could relate to atherosclerosis in humans and that this effect could interact with the dietary intake of competing 5-lipoxygenase substrates. (
  • 5‐LOX products are involved in inflammation, allergic reactions, development of cardiovascular disease as well as certain types of cancer. (
  • Immediately following these plenary lectures, three simultaneous breakout sessions were held, one of inflammation, a second on cancer and synthesis of novel inhibitors, and a third on enzymes-lipoxygenases/cyclooxygenases and inhibitors. (
  • Medisyn's approach will involve identification of inhibitors for both cyclooxygenase-2 (COX-2) and arachidonate 5-lipoxygenase (5-LO), two potent mediators of inflammation. (
  • and 3) consume a diet high in fruits, vegetables, nuts, and whole grains and low in refined grains ( Fig. 1 ).The effects of diet on CHD can be mediated through multiple biologic pathways other than serum lipids, including oxidative stress, subclinical inflammation, endothelial dysfunction, insulin sensitivity, blood pressure, and thrombotic tendency ( 5 ). (
  • 1981) Inflammation 5(1):13-17. (
  • We examined the effects of an inhibitor of 5-lipoxygenase, zileuton, in a group of eight asthmatic patients with known sensitivity to ASA accompanied by LTE4 hyperexcretion. (
  • The phospho-specific antibody to Ser523 on 5-LO is thus likely to provide a valuable tool for studies of the role of 5-LO regulation in diseases such as asthma, fibrosis and atherosclerosis. (
  • It was also found that the active 5-lipoxygenase metabolite, 5-oxoETE (a dehydrogenated derive of 5(S)-HETE), signals via its cognate receptor, called OXER1, which is a member of the seven-transmembrane G proteincoupled receptor (GPCR) family. (
  • Acetohydroxamic acids as potent, selective, orally active 5-lipoxygenase inhibitors. (
  • Inhibitors of its function impede translocation of 5-lipoxygenase from the cytoplasm to the cell membrane and inhibit 5-lipoxygenase activation. (
  • The same extract was also found to inhibit lipoxygenase and xanthine oxidase enzymes in a concentration-dependent manner with an IC 50 of 128.20±3.39 and 144.23±2.04 μg/ml for lipoxygenase and xanthine oxidase, respectively. (
  • Omega 3 fatty acids inhibit tumor growth by a number of mechanisms including suppression of COX-2 expression and, for EPA at least, the alternative substrate produces different cyclooxygenase (PGE 3 ) and lipoxygenase (LTB 5 ) products that have anti-inflammatory and anticancer effects. (
  • THE 5-LOX interface involving the four cysteines 159, 300, 416 and 418 is important for the translocation to the nuclear membrane and the colocalization with FLAP. (
  • 5‐LOX interacts with various proteins such as FLAP, CLP and Dicer. (
  • Upon cell stimulation soluble 5‐LOX binds Ca 2+ and may become phosphorylated, and then translocates to the nuclear envelope where it binds to the outer or inner nuclear membrane via Ca 2+ close to membrane‐integrated FLAP . (
  • AA liberated by cPLA 2 is transferred via FLAP to 5‐LOX producing LTA 4 that is converted by LTC 4 S (cytosolic side) or LTA 4 H (intranuclear) to LTC 4 or LTB 4 , respectively. (
  • 5-Lipoxygenase-Activating Proteins" is a descriptor in the National Library of Medicine's controlled vocabulary thesaurus, MeSH (Medical Subject Headings) . (
  • Scaffolding proteins that play an important role in the localization and activation of 5-LIPOXYGENASE. (
  • This graph shows the total number of publications written about "5-Lipoxygenase-Activating Proteins" by people in Harvard Catalyst Profiles by year, and whether "5-Lipoxygenase-Activating Proteins" was a major or minor topic of these publication. (
  • Below are the most recent publications written about "5-Lipoxygenase-Activating Proteins" by people in Profiles. (
  • 5-HETE, 5-oxo-6,8,11,14- E,Z,Z,Z -eicosatetraenoate, and 5-oxo-15-hydroxy-eicosatetraenoate are known to stimulate leukocytes by a receptor coupled to pertussis toxin-sensitive G proteins. (
  • (10) have identified a gene encoding a GPCR that mediates responses to 5-HETE, couples to PT-sensitive G proteins, and, based on these and other data, may be the leukocyte 5-HETE receptor. (
  • Examples of 5-LOX inhibitors include drugs, such as meclofenamate sodium and zileuton. (
  • The arachidonate 5-lipoxygenase activating protein gene polymorphism is associated with the risk of scleroderma-related interstitial lung disease: a multicentre European Scleroderma Trials and Research group (EUSTAR) study. (
  • 1993) 5‐Lipoxygenase‐activating protein stimulates the utilization of arachidonic acid by 5‐lipoxygenase. (
  • BC018538 - Homo sapiens arachidonate 5-lipoxygenase-activating protein, mRNA (cDNA clone MGC:17120 IMAGE:4342203), complete cds. (
  • In (b), PKCε was first isolated from untreated LNCaP cells and then treated with 5-oxoETE or MK591 (10 μM) for 10 min in the assay buffer. (
  • Antiproliferative activity was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. (
  • Kermode J C et al: "Characteristics of binding of a potent chemotactic formyl tetrapeptide, formylmethionyl-leucyl-phenylalanyl-phenyl alanine, to the receptors on rabbit neutrophils" Journal of Leukocyte Biology vol. 43, No. 5, 1988, pp. 420-428, XP001029129 ISSN: 0741-5400. (
  • 5) Each step is characterized by a different repertoire of G protein-coupled receptors, with five nucleotide receptors as novel M2-associated genes. (
  • Your search returned 257 5-Lipoxygenase ELISA ELISA Kit across 14 suppliers. (
  • However, mechanisms by which 5-Lox metabolites activate PKCε are not understood yet. (
  • How 5-lipoxygenase metabolites exert survival-promoting effects in prostate cancer cells was the topic of great interest in the last decade. (
  • Possible vasoconstrictor mediators include arachidonic acid-derived lipoxygenase (LO) metabolites. (
  • Nonredox-type 5-lipoxygenase (5-LO) inhibitors such as ZM230487 or L-739.010 potently suppress leukotriene biosynthesis at low cellular peroxide tone. (
  • 5‐LOX is also involved in the biosynthesis of anti‐inflammatory/pro‐resolving lipoxins. (
  • Leukotriene B4, along with some of the mono-hydroxy lipoxygenase products is chemotactic and it has been suggested that LTB4 production by activated PMNs represents a local control mechanism for the accumulation of leukocytes at inflammatory sites. (
  • The effects of a novel series of selective inhibitors of arachidonate 5-lipoxygenase on anaphylactic and inflammatory responses. (
  • 2004). Recent work has demonstrated that the activity of 5-LO is regulated by PKA phosphorylation of serine-523 in 5-LO (Luo et al. (
  • Intriguingly, a significant difference in the potency of nonredox-type inhibitors (but not of BWA4C) was determined between wild-type 5-LO and the mutant S271A/S663A-5-LO (lacking phosphorylation sites for ERK1/2 and MAPKAPK-2) in HeLa cells. (
  • Collectively, our data suggest that compared with Ca2+-mediated 5-LO product formation, enzyme activation involving 5-LO phosphorylation events specifically and strongly alters the susceptibility of 5-LO toward nonredox-type inhibitors in intact cells. (
  • Synthesized phosphopeptide derived from human 5 Lipoxygenase around the phosphorylation site of serine 271. (
  • Synthesized non phosphopeptide derived from human 5 lipoxygenase around the phosphorylation site of serine 271 (QLS P LE). (
  • 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. (
  • 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 . (
  • K-Ras is the isoform that is most frequently mutated in human cancers ( 5 ). (
  • Another important activity for hyperforin is a dual inhibitor of cyclooxygenase-1 and 5-lipoxygenase [59]. (
  • 6 The combined cyclooxygenase/lipoxygenase (LO) inhibitor BW 755C completely blocked contractions in the females. (
  • Both the R(+) and S(-) enantiomers are pharmacologically active as 5-lipoxygenase inhibitors in in vitro systems. (
  • Hyperforin turned out to be a novel type of 5-lipoxygenase inhibitor with high effectivity in vivo [55] and suppressed oxidative bursts in polymorphonuclear cells at 1.8 µmol/L in vitro [56]. (
  • To examine the nature of the in vitro inhibitory effect of lobaric acid on 5-lipoxygenase observed earlier, investigations were undertaken to study the effects of lobaric acid on ionophore A23187 induced contractions in the smooth muscle taenia coli from guinea pigs. (
  • In vitro Evaluation of Antiproliferative, Lipoxygenase and Xanthine Oxidase Inhibitory Activities of Artemisia nilagirica (C.B.Clarke) Pamp. (
  • 2017 May 1;56(5):844-852. (
  • 2017 May;69(5):1028-1034. (
  • We found that prostate cancer cells express high levels of OXER1, a G protein-coupled 5-oxoETE receptor, which delivers signal by generating diacyl-glycerol through phospholipase C-beta. (
  • a) Model of human wildtype 5‐LOX derived from the crystal structure of stable 5‐LOX (PDB: 3o8y). (
  • Human aortic endothelial cells cultured in chronically high glucose levels results in elevated levels of 12S-HETE, suggesting activation of lipoxygenase pathways [ 12 , 13 ]. (
  • Mammalian lipoxygenases possess regiospecificity during interaction with substrate, and on this basis have been designated as arachidonate 5-, 12-, and 15-lipoxygenase (5-LOX, 12-LOX, and 15-LOX) [ 14 - 16 ]. (