Cyclooxygenase 2: An inducibly-expressed subtype of prostaglandin-endoperoxide synthase. It plays an important role in many cellular processes and INFLAMMATION. It is the target of COX2 INHIBITORS.Cyclooxygenase 1: A constitutively-expressed subtype of prostaglandin-endoperoxide synthase. It plays an important role in many cellular processes.Cyclooxygenase Inhibitors: Compounds or agents that combine with cyclooxygenase (PROSTAGLANDIN-ENDOPEROXIDE SYNTHASES) and thereby prevent its substrate-enzyme combination with arachidonic acid and the formation of eicosanoids, prostaglandins, and thromboxanes.Protein Isoforms: Different forms of a protein that may be produced from different GENES, or from the same gene by ALTERNATIVE SPLICING.Cyclooxygenase 2 Inhibitors: A subclass of cyclooxygenase inhibitors with specificity for CYCLOOXYGENASE-2.Prostaglandin-Endoperoxide Synthases: Enzyme complexes that catalyze the formation of PROSTAGLANDINS from the appropriate unsaturated FATTY ACIDS, molecular OXYGEN, and a reduced acceptor.Isoenzymes: Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.Dinoprostone: The most common and most biologically active of the mammalian prostaglandins. It exhibits most biological activities characteristic of prostaglandins and has been used extensively as an oxytocic agent. The compound also displays a protective effect on the intestinal mucosa.Indomethacin: A non-steroidal anti-inflammatory agent (NSAID) that inhibits the enzyme cyclooxygenase necessary for the formation of prostaglandins and other autacoids. It also inhibits the motility of polymorphonuclear leukocytes.Prostaglandins: A group of compounds derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway. They are extremely potent mediators of a diverse group of physiological processes.Arachidonic Acid: An unsaturated, essential fatty acid. It is found in animal and human fat as well as in the liver, brain, and glandular organs, and is a constituent of animal phosphatides. It is formed by the synthesis from dietary linoleic acid and is a precursor in the biosynthesis of prostaglandins, thromboxanes, and leukotrienes.NitrobenzenesAnti-Inflammatory Agents, Non-Steroidal: Anti-inflammatory agents that are non-steroidal in nature. In addition to anti-inflammatory actions, they have analgesic, antipyretic, and platelet-inhibitory actions.They act by blocking the synthesis of prostaglandins by inhibiting cyclooxygenase, which converts arachidonic acid to cyclic endoperoxides, precursors of prostaglandins. Inhibition of prostaglandin synthesis accounts for their analgesic, antipyretic, and platelet-inhibitory actions; other mechanisms may contribute to their anti-inflammatory effects.Sulfonamides: A group of compounds that contain the structure SO2NH2.Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.Pyrazoles: Azoles of two nitrogens at the 1,2 positions, next to each other, in contrast with IMIDAZOLES in which they are at the 1,3 positions.Lipoxygenase Inhibitors: Compounds that bind to and inhibit that enzymatic activity of LIPOXYGENASES. Included under this category are inhibitors that are specific for lipoxygenase subtypes and act to reduce the production of LEUKOTRIENES.Ibuprofen: A nonsteroidal anti-inflammatory agent with analgesic properties used in the therapy of rheumatism and arthritis.Thromboxane B2: A stable, physiologically active compound formed in vivo from the prostaglandin endoperoxides. It is important in the platelet-release reaction (release of ADP and serotonin).RNA, Messenger: RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.Arachidonic Acids6-Ketoprostaglandin F1 alpha: The physiologically active and stable hydrolysis product of EPOPROSTENOL. Found in nearly all mammalian tissue.Alternative Splicing: A process whereby multiple RNA transcripts are generated from a single gene. Alternative splicing involves the splicing together of other possible sets of EXONS during the processing of some, but not all, transcripts of the gene. Thus a particular exon may be connected to any one of several alternative exons to form a mature RNA. The alternative forms of mature MESSENGER RNA produce PROTEIN ISOFORMS in which one part of the isoforms is common while the other parts are different.Proportional Hazards Models: Statistical models used in survival analysis that assert that the effect of the study factors on the hazard rate in the study population is multiplicative and does not change over time.Eicosanoids: A class of compounds named after and generally derived from C20 fatty acids (EICOSANOIC ACIDS) that includes PROSTAGLANDINS; LEUKOTRIENES; THROMBOXANES, and HYDROXYEICOSATETRAENOIC ACIDS. They have hormone-like effects mediated by specialized receptors (RECEPTORS, EICOSANOID).Flurbiprofen: An anti-inflammatory analgesic and antipyretic of the phenylalkynoic acid series. It has been shown to reduce bone resorption in periodontal disease by inhibiting CARBONIC ANHYDRASE.Lipoxygenase: An enzyme of the oxidoreductase class primarily found in PLANTS. It catalyzes reactions between linoleate and other fatty acids and oxygen to form hydroperoxy-fatty acid derivatives.Aspirin: The prototypical analgesic used in the treatment of mild to moderate pain. It has anti-inflammatory and antipyretic properties and acts as an inhibitor of cyclooxygenase which results in the inhibition of the biosynthesis of prostaglandins. Aspirin also inhibits platelet aggregation and is used in the prevention of arterial and venous thrombosis. (From Martindale, The Extra Pharmacopoeia, 30th ed, p5)Epoprostenol: A prostaglandin that is a powerful vasodilator and inhibits platelet aggregation. It is biosynthesized enzymatically from PROSTAGLANDIN ENDOPEROXIDES in human vascular tissue. The sodium salt has been also used to treat primary pulmonary hypertension (HYPERTENSION, PULMONARY).Masoprocol: A potent lipoxygenase inhibitor that interferes with arachidonic acid metabolism. The compound also inhibits formyltetrahydrofolate synthetase, carboxylesterase, and cyclooxygenase to a lesser extent. It also serves as an antioxidant in fats and oils.Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.Cells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.Piroxicam: A cyclooxygenase inhibiting, non-steroidal anti-inflammatory agent (NSAID) that is well established in treating rheumatoid arthritis and osteoarthritis and used for musculoskeletal disorders, dysmenorrhea, and postoperative pain. Its long half-life enables it to be administered once daily.Diclofenac: A non-steroidal anti-inflammatory agent (NSAID) with antipyretic and analgesic actions. It is primarily available as the sodium salt.Intramolecular Oxidoreductases: Enzymes of the isomerase class that catalyze the oxidation of one part of a molecule with a corresponding reduction of another part of the same molecule. They include enzymes converting aldoses to ketoses (ALDOSE-KETOSE ISOMERASES), enzymes shifting a carbon-carbon double bond (CARBON-CARBON DOUBLE BOND ISOMERASES), and enzymes transposing S-S bonds (SULFUR-SULFUR BOND ISOMERASES). (From Enzyme Nomenclature, 1992) EC 5.3.Receptors, Prostaglandin E: Cell surface receptors which bind prostaglandins with a high affinity and trigger intracellular changes which influence the behavior of cells. Prostaglandin E receptors prefer prostaglandin E2 to other endogenous prostaglandins. They are subdivided into EP1, EP2, and EP3 types based on their effects and their pharmacology.Gene Expression Regulation, Enzymologic: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis.Thromboxane A2: An unstable intermediate between the prostaglandin endoperoxides and thromboxane B2. The compound has a bicyclic oxaneoxetane structure. It is a potent inducer of platelet aggregation and causes vasoconstriction. It is the principal component of rabbit aorta contracting substance (RCS).Blotting, Western: 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.Electron Transport Complex IV: A multisubunit enzyme complex containing CYTOCHROME A GROUP; CYTOCHROME A3; two copper atoms; and 13 different protein subunits. It is the terminal oxidase complex of the RESPIRATORY CHAIN and collects electrons that are transferred from the reduced CYTOCHROME C GROUP and donates them to molecular OXYGEN, which is then reduced to water. The redox reaction is simultaneously coupled to the transport of PROTONS across the inner mitochondrial membrane.Naproxen: An anti-inflammatory agent with analgesic and antipyretic properties. Both the acid and its sodium salt are used in the treatment of rheumatoid arthritis and other rheumatic or musculoskeletal disorders, dysmenorrhea, and acute gout.Arachidonate 5-Lipoxygenase: An enzyme that catalyzes the oxidation of arachidonic acid to yield 5-hydroperoxyarachidonate (5-HPETE) which is rapidly converted by a peroxidase to 5-hydroxy-6,8,11,14-eicosatetraenoate (5-HETE). The 5-hydroperoxides are preferentially formed in leukocytes.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Isomerism: The phenomenon whereby certain chemical compounds have structures that are different although the compounds possess the same elemental composition. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 5th ed)Thromboxane-A Synthase: An enzyme found predominantly in platelet microsomes. It catalyzes the conversion of PGG(2) and PGH(2) (prostaglandin endoperoxides) to thromboxane A2. EC 5.3.99.5.Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.ThiazinesHydroxyeicosatetraenoic Acids: Eicosatetraenoic acids substituted in any position by one or more hydroxy groups. They are important intermediates in a series of biosynthetic processes leading from arachidonic acid to a number of biologically active compounds such as prostaglandins, thromboxanes, and leukotrienes.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Rats, Sprague-Dawley: A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.Nitric Oxide Synthase: An NADPH-dependent enzyme that catalyzes the conversion of L-ARGININE and OXYGEN to produce CITRULLINE and NITRIC OXIDE.RNA Isoforms: The different gene transcripts generated from a single gene by RNA EDITING or ALTERNATIVE SPLICING of RNA PRECURSORS.Reverse Transcriptase Polymerase Chain Reaction: A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.Thromboxanes: Physiologically active compounds found in many organs of the body. They are formed in vivo from the prostaglandin endoperoxides and cause platelet aggregation, contraction of arteries, and other biological effects. Thromboxanes are important mediators of the actions of polyunsaturated fatty acids transformed by cyclooxygenase.Meclofenamic Acid: A non-steroidal anti-inflammatory agent with antipyretic and antigranulation activities. It also inhibits prostaglandin biosynthesis.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Dinoprost: A naturally occurring prostaglandin that has oxytocic, luteolytic, and abortifacient activities. Due to its vasocontractile properties, the compound has a variety of other biological actions.Nitric Oxide: A free radical gas produced endogenously by a variety of mammalian cells, synthesized from ARGININE by NITRIC OXIDE SYNTHASE. Nitric oxide is one of the ENDOTHELIUM-DEPENDENT RELAXING FACTORS released by the vascular endothelium and mediates VASODILATION. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic GUANYLATE CYCLASE and thus elevates intracellular levels of CYCLIC GMP.SulfonesCell Line: Established cell cultures that have the potential to propagate indefinitely.Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.Enzyme Induction: An increase in the rate of synthesis of an enzyme due to the presence of an inducer which acts to derepress the gene responsible for enzyme synthesis.Prostaglandins G: A group of physiologically active prostaglandin endoperoxides. They are precursors in the biosynthesis of prostaglandins and thromboxanes. Most frequently encountered member of this group is the prostaglandin G2.Seminal Vesicles: A saclike, glandular diverticulum on each ductus deferens in male vertebrates. It is united with the excretory duct and serves for temporary storage of semen. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)Lactones: Cyclic esters of hydroxy carboxylic acids, containing a 1-oxacycloalkan-2-one structure. Large cyclic lactones of over a dozen atoms are MACROLIDES.Phospholipases A: Phospholipases that hydrolyze one of the acyl groups of phosphoglycerides or glycerophosphatidates.5,8,11,14-Eicosatetraynoic Acid: A 20-carbon unsaturated fatty acid containing 4 alkyne bonds. It inhibits the enzymatic conversion of arachidonic acid to prostaglandins E(2) and F(2a).Phospholipases A2: Phospholipases that hydrolyze the acyl group attached to the 2-position of PHOSPHOGLYCERIDES.Signal Transduction: The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.Vasodilation: The physiological widening of BLOOD VESSELS by relaxing the underlying VASCULAR SMOOTH MUSCLE.4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine: A dual inhibitor of both cyclooxygenase and lipoxygenase pathways. It exerts an anti-inflammatory effect by inhibiting the formation of prostaglandins and leukotrienes. The drug also enhances pulmonary hypoxic vasoconstriction and has a protective effect after myocardial ischemia.Endothelium, Vascular: Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components.Prostaglandins E: (11 alpha,13E,15S)-11,15-Dihydroxy-9-oxoprost-13-en-1-oic acid (PGE(1)); (5Z,11 alpha,13E,15S)-11,15-dihydroxy-9-oxoprosta-5,13-dien-1-oic acid (PGE(2)); and (5Z,11 alpha,13E,15S,17Z)-11,15-dihydroxy-9-oxoprosta-5,13,17-trien-1-oic acid (PGE(3)). Three of the six naturally occurring prostaglandins. They are considered primary in that no one is derived from another in living organisms. Originally isolated from sheep seminal fluid and vesicles, they are found in many organs and tissues and play a major role in mediating various physiological activities.Prognosis: A prediction of the probable outcome of a disease based on a individual's condition and the usual course of the disease as seen in similar situations.Rats, Wistar: A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.Sulindac: A sulfinylindene derivative prodrug whose sulfinyl moiety is converted in vivo to an active NSAID analgesic. Specifically, the prodrug is converted by liver enzymes to a sulfide which is excreted in the bile and then reabsorbed from the intestine. This helps to maintain constant blood levels with reduced gastrointestinal side effects.Ketorolac: A pyrrolizine carboxylic acid derivative structurally related to INDOMETHACIN. It is an NSAID and is used principally for its analgesic activity. (From Martindale The Extra Pharmacopoeia, 31st ed)Receptors, Thromboxane: Cell surface proteins that bind THROMBOXANES with high affinity and trigger intracellular changes influencing the behavior of cells. Some thromboxane receptors act via the inositol phosphate and diacylglycerol second messenger systems.Leukotrienes: A family of biologically active compounds derived from arachidonic acid by oxidative metabolism through the 5-lipoxygenase pathway. They participate in host defense reactions and pathophysiological conditions such as immediate hypersensitivity and inflammation. They have potent actions on many essential organs and systems, including the cardiovascular, pulmonary, and central nervous system as well as the gastrointestinal tract and the immune system.Kinetics: The rate dynamics in chemical or physical systems.Prostaglandin H2: A cyclic endoperoxide intermediate produced by the action of CYCLOOXYGENASE on ARACHIDONIC ACID. It is further converted by a series of specific enzymes to the series 2 prostaglandins.8,11,14-Eicosatrienoic Acid: A 20-carbon-chain fatty acid, unsaturated at positions 8, 11, and 14. It differs from arachidonic acid, 5,8,11,14-eicosatetraenoic acid, only at position 5.Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.Vasoconstriction: The physiological narrowing of BLOOD VESSELS by contraction of the VASCULAR SMOOTH MUSCLE.Risk Factors: An aspect of personal behavior or lifestyle, environmental exposure, or inborn or inherited characteristic, which, on the basis of epidemiologic evidence, is known to be associated with a health-related condition considered important to prevent.Receptors, Prostaglandin E, EP4 Subtype: A subtype of prostaglandin E receptors that specifically couples to GS ALPHA GTP-BINDING PROTEIN SUBUNITS and subsequently activates ADENYLYL CYCLASES. The receptor may also signal through the activation of PHOSPHATIDYLINOSITOL 3-KINASE.Receptors, Prostaglandin E, EP1 Subtype: A subtype of prostaglandin E receptors that specifically couples to GTP-BINDING PROTEIN ALPHA SUBUNIT, GQ and the subsequently activates TYPE C PHOSPHOLIPASES. Additional evidence has shown that the receptor can act through a calcium-dependent signaling pathway.Prostaglandin D2: The principal cyclooxygenase metabolite of arachidonic acid. It is released upon activation of mast cells and is also synthesized by alveolar macrophages. Among its many biological actions, the most important are its bronchoconstrictor, platelet-activating-factor-inhibitory, and cytotoxic effects.Cloning, Molecular: 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.DNA, Complementary: Single-stranded complementary DNA synthesized from an RNA template by the action of RNA-dependent DNA polymerase. cDNA (i.e., complementary DNA, not circular DNA, not C-DNA) is used in a variety of molecular cloning experiments as well as serving as a specific hybridization probe.Bradykinin: A nonapeptide messenger that is enzymatically produced from KALLIDIN in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from MAST CELLS during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter.Mice, Inbred C57BLTransfection: The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.Arachidonate Lipoxygenases: Enzymes catalyzing the oxidation of arachidonic acid to hydroperoxyarachidonates. These products are then rapidly converted by a peroxidase to hydroxyeicosatetraenoic acids. The positional specificity of the enzyme reaction varies from tissue to tissue. The final lipoxygenase pathway leads to the leukotrienes. EC 1.13.11.- .Cohort Studies: Studies in which subsets of a defined population are identified. These groups may or may not be exposed to factors hypothesized to influence the probability of the occurrence of a particular disease or other outcome. Cohorts are defined populations which, as a whole, are followed in an attempt to determine distinguishing subgroup characteristics.Enzyme Activation: Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.Protein Kinase C: An serine-threonine protein kinase that requires the presence of physiological concentrations of CALCIUM and membrane PHOSPHOLIPIDS. The additional presence of DIACYLGLYCEROLS markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by PHORBOL ESTERS and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters.Sheep: Any of the ruminant mammals with curved horns in the genus Ovis, family Bovidae. They possess lachrymal grooves and interdigital glands, which are absent in GOATS.Lipopolysaccharides: Lipid-containing polysaccharides which are endotoxins and important group-specific antigens. They are often derived from the cell wall of gram-negative bacteria and induce immunoglobulin secretion. The lipopolysaccharide molecule consists of three parts: LIPID A, core polysaccharide, and O-specific chains (O ANTIGENS). When derived from Escherichia coli, lipopolysaccharides serve as polyclonal B-cell mitogens commonly used in laboratory immunology. (From Dorland, 28th ed)Gene Expression Regulation: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.Rabbits: The species Oryctolagus cuniculus, in the family Leporidae, order LAGOMORPHA. Rabbits are born in burrows, furless, and with eyes and ears closed. In contrast with HARES, rabbits have 22 chromosome pairs.Blood Platelets: Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation.HydrazinesCalcimycin: An ionophorous, polyether antibiotic from Streptomyces chartreusensis. It binds and transports CALCIUM and other divalent cations across membranes and uncouples oxidative phosphorylation while inhibiting ATPase of rat liver mitochondria. The substance is used mostly as a biochemical tool to study the role of divalent cations in various biological systems.Leukotriene B4: The major metabolite in neutrophil polymorphonuclear leukocytes. It stimulates polymorphonuclear cell function (degranulation, formation of oxygen-centered free radicals, arachidonic acid release, and metabolism). (From Dictionary of Prostaglandins and Related Compounds, 1990)Recombinant Proteins: Proteins prepared by recombinant DNA technology.Sequence Homology, Amino Acid: The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.Receptors, Prostaglandin E, EP2 Subtype: A subtype of prostaglandin E receptors that specifically couples to GS ALPHA GTP-BINDING PROTEIN SUBUNITS and subsequently activates ADENYLYL CYCLASES.Interleukin-1: A soluble factor produced by MONOCYTES; MACROPHAGES, and other cells which activates T-lymphocytes and potentiates their response to mitogens or antigens. Interleukin-1 is a general term refers to either of the two distinct proteins, INTERLEUKIN-1ALPHA and INTERLEUKIN-1BETA. The biological effects of IL-1 include the ability to replace macrophage requirements for T-cell activation.Mice, Knockout: Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.NG-Nitroarginine Methyl Ester: A non-selective inhibitor of nitric oxide synthase. It has been used experimentally to induce hypertension.Prostaglandin Antagonists: Compounds that inhibit the action of prostaglandins.Survival Analysis: A class of statistical procedures for estimating the survival function (function of time, starting with a population 100% well at a given time and providing the percentage of the population still well at later times). The survival analysis is then used for making inferences about the effects of treatments, prognostic factors, exposures, and other covariates on the function.Exons: The parts of a transcript of a split GENE remaining after the INTRONS are removed. They are spliced together to become a MESSENGER RNA or other functional RNA.Receptors, Prostaglandin: Cell surface receptors that bind prostaglandins with high affinity and trigger intracellular changes which influence the behavior of cells. Prostaglandin receptor subtypes have been tentatively named according to their relative affinities for the endogenous prostaglandins. They include those which prefer prostaglandin D2 (DP receptors), prostaglandin E2 (EP1, EP2, and EP3 receptors), prostaglandin F2-alpha (FP receptors), and prostacyclin (IP receptors).Follow-Up Studies: Studies in which individuals or populations are followed to assess the outcome of exposures, procedures, or effects of a characteristic, e.g., occurrence of disease.Salicylates: 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.DNA Primers: Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.Tolmetin: A non-steroidal anti-inflammatory agent (ANTI-INFLAMMATORY AGENTS, NON-STEROIDAL) similar in mode of action to INDOMETHACIN.Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.Cytochrome P-450 Enzyme System: A superfamily of hundreds of closely related HEMEPROTEINS found throughout the phylogenetic spectrum, from animals, plants, fungi, to bacteria. They include numerous complex monooxygenases (MIXED FUNCTION OXYGENASES). In animals, these P-450 enzymes serve two major functions: (1) biosynthesis of steroids, fatty acids, and bile acids; (2) metabolism of endogenous and a wide variety of exogenous substrates, such as toxins and drugs (BIOTRANSFORMATION). They are classified, according to their sequence similarities rather than functions, into CYP gene families (>40% homology) and subfamilies (>59% homology). For example, enzymes from the CYP1, CYP2, and CYP3 gene families are responsible for most drug metabolism.Up-Regulation: A positive regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.Nitric Oxide Synthase Type II: A CALCIUM-independent subtype of nitric oxide synthase that may play a role in immune function. It is an inducible enzyme whose expression is transcriptionally regulated by a variety of CYTOKINES.Microsomes: 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)PeroxidasesProspective Studies: Observation of a population for a sufficient number of persons over a sufficient number of years to generate incidence or mortality rates subsequent to the selection of the study group.Prostaglandins H: A group of physiologically active prostaglandin endoperoxides. They are precursors in the biosynthesis of prostaglandins and thromboxanes. The most frequently encountered member of this group is the prostaglandin H2.Kaplan-Meier Estimate: A nonparametric method of compiling LIFE TABLES or survival tables. It combines calculated probabilities of survival and estimates to allow for observations occurring beyond a measurement threshold, which are assumed to occur randomly. Time intervals are defined as ending each time an event occurs and are therefore unequal. (From Last, A Dictionary of Epidemiology, 1995)Receptors, Thromboxane A2, Prostaglandin H2: A subclass of eicosanoid receptors that have specificity for THROMBOXANE A2 and PROSTAGLANDIN H2.Platelet Aggregation: The attachment of PLATELETS to one another. This clumping together can be induced by a number of agents (e.g., THROMBIN; COLLAGEN) and is part of the mechanism leading to the formation of a THROMBUS.Receptors, Prostaglandin E, EP3 Subtype: A subtype of prostaglandin E receptors that specifically couples to GTP-BINDING PROTEIN ALPHA SUBUNIT, GI and subsequently inhibits ADENYLYL CYCLASES.Transcription, Genetic: The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.Inflammation: 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.Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.Ketoprofen: An IBUPROFEN-type anti-inflammatory analgesic and antipyretic. It is used in the treatment of rheumatoid arthritis and osteoarthritis.12-Hydroxy-5,8,10,14-eicosatetraenoic Acid: A lipoxygenase metabolite of ARACHIDONIC ACID. It is a highly selective ligand used to label mu-opioid receptors in both membranes and tissue sections. The 12-S-HETE analog has been reported to augment tumor cell metastatic potential through activation of protein kinase C. (J Pharmacol Exp Ther 1995; 274(3):1545-51; J Natl Cancer Inst 1994; 86(15):1145-51)Cell Line, Tumor: A cell line derived from cultured tumor cells.15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid: A stable prostaglandin endoperoxide analog which serves as a thromboxane mimetic. Its actions include mimicking the hydro-osmotic effect of VASOPRESSIN and activation of TYPE C PHOSPHOLIPASES. (From J Pharmacol Exp Ther 1983;224(1): 108-117; Biochem J 1984;222(1):103-110)Vasodilator Agents: Drugs used to cause dilation of the blood vessels.Immunoblotting: Immunologic method used for detecting or quantifying immunoreactive substances. The substance is identified by first immobilizing it by blotting onto a membrane and then tagging it with labeled antibodies.Muscle, Smooth, Vascular: The nonstriated involuntary muscle tissue of blood vessels.Blotting, Northern: Detection of RNA that has been electrophoretically separated and immobilized by blotting on nitrocellulose or other type of paper or nylon membrane followed by hybridization with labeled NUCLEIC ACID PROBES.Kidney: Body organ that filters blood for the secretion of URINE and that regulates ion concentrations.Tumor Cells, Cultured: 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.Survival Rate: The proportion of survivors in a group, e.g., of patients, studied and followed over a period, or the proportion of persons in a specified group alive at the beginning of a time interval who survive to the end of the interval. It is often studied using life table methods.Chromatography, High Pressure Liquid: Liquid chromatographic techniques which feature high inlet pressures, high sensitivity, and high speed.Nitroarginine: An inhibitor of nitric oxide synthetase which has been shown to prevent glutamate toxicity. Nitroarginine has been experimentally tested for its ability to prevent ammonia toxicity and ammonia-induced alterations in brain energy and ammonia metabolites. (Neurochem Res 1995:200(4):451-6)Acetylcholine: A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system.Vasoconstrictor Agents: Drugs used to cause constriction of the blood vessels.Disease Models, Animal: Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.Macrophages: The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.)Apoptosis: One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.Mutation: Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.Gastric Mucosa: Lining of the STOMACH, consisting of an inner EPITHELIUM, a middle LAMINA PROPRIA, and an outer MUSCULARIS MUCOSAE. The surface cells produce MUCUS that protects the stomach from attack by digestive acid and enzymes. When the epithelium invaginates into the LAMINA PROPRIA at various region of the stomach (CARDIA; GASTRIC FUNDUS; and PYLORUS), different tubular gastric glands are formed. These glands consist of cells that secrete mucus, enzymes, HYDROCHLORIC ACID, or hormones.Protein Structure, Tertiary: The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.Retrospective Studies: Studies used to test etiologic hypotheses in which inferences about an exposure to putative causal factors are derived from data relating to characteristics of persons under study or to events or experiences in their past. The essential feature is that some of the persons under study have the disease or outcome of interest and their characteristics are compared with those of unaffected persons.Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.Myosin Heavy Chains: The larger subunits of MYOSINS. The heavy chains have a molecular weight of about 230 kDa and each heavy chain is usually associated with a dissimilar pair of MYOSIN LIGHT CHAINS. The heavy chains possess actin-binding and ATPase activity.Anti-Inflammatory Agents: Substances that reduce or suppress INFLAMMATION.Cytochrome-c Oxidase Deficiency: A disease that results from a congenital defect in ELECTRON TRANSPORT COMPLEX IV. Defects in ELECTRON TRANSPORT COMPLEX IV can be caused by mutations in the SURF1, SCO2, COX10, or SCO1 genes. ELECTRON TRANSPORT COMPLEX IV deficiency caused by mutation in SURF1 manifests itself as LEIGH DISEASE; that caused by mutation in SCO2 as fatal infantile cardioencephalomyopathy; that caused by mutation in COX10 as tubulopathy and leukodystrophy; and that caused by mutation in SCO1 as early-onset hepatic failure and neurologic disorder. (from Online Mendelian Inheritance in Man, http://www.ncbi.nlm.nih.gov/Omim, MIM#220110, May 17, 2001)Biological Factors: Endogenously-synthesized compounds that influence biological processes not otherwise classified under ENZYMES; HORMONES or HORMONE ANTAGONISTS.Hydroxyprostaglandin Dehydrogenases: Catalyzes reversibly the oxidation of hydroxyl groups of prostaglandins.Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.Muscle, Skeletal: A subtype of striated muscle, attached by TENDONS to the SKELETON. Skeletal muscles are innervated and their movement can be consciously controlled. They are also called voluntary muscles.Multivariate Analysis: A set of techniques used when variation in several variables has to be studied simultaneously. In statistics, multivariate analysis is interpreted as any analytic method that allows simultaneous study of two or more dependent variables.Ketorolac Tromethamine: A pyrrolizine carboxylic acid derivative structurally related to INDOMETHACIN. It is a non-steroidal anti-inflammatory agent used for analgesia for postoperative pain and inhibits cyclooxygenase activity.Phospholipases A2, Cytosolic: A subcategory of phospholipases A2 that occur in the CYTOSOL.Tetradecanoylphorbol Acetate: A phorbol ester found in CROTON OIL with very effective tumor promoting activity. It stimulates the synthesis of both DNA and RNA.Dogs: The domestic dog, Canis familiaris, comprising about 400 breeds, of the carnivore family CANIDAE. They are worldwide in distribution and live in association with people. (Walker's Mammals of the World, 5th ed, p1065)SRS-A: A group of LEUKOTRIENES; (LTC4; LTD4; and LTE4) that is the major mediator of BRONCHOCONSTRICTION; HYPERSENSITIVITY; and other allergic reactions. Earlier studies described a "slow-reacting substance of ANAPHYLAXIS" released from lung by cobra venom or after anaphylactic shock. The relationship between SRS-A leukotrienes was established by UV which showed the presence of the conjugated triene. (From Merck Index, 11th ed)Treatment Outcome: Evaluation undertaken to assess the results or consequences of management and procedures used in combating disease in order to determine the efficacy, effectiveness, safety, and practicability of these interventions in individual cases or series.NF-kappa B: Ubiquitous, inducible, nuclear transcriptional activator that binds to enhancer elements in many different cell types and is activated by pathogenic stimuli. The NF-kappa B complex is a heterodimer composed of two DNA-binding subunits: NF-kappa B1 and relA.Brain: The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.Electrophoresis, Polyacrylamide Gel: Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.Polymerase Chain Reaction: In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships.Sequence Alignment: The arrangement of two or more amino acid or base sequences from an organism or organisms in such a way as to align areas of the sequences sharing common properties. The degree of relatedness or homology between the sequences is predicted computationally or statistically based on weights assigned to the elements aligned between the sequences. This in turn can serve as a potential indicator of the genetic relatedness between the organisms.Colonic Neoplasms: Tumors or cancer of the COLON.Promoter Regions, Genetic: DNA sequences which are recognized (directly or indirectly) and bound by a DNA-dependent RNA polymerase during the initiation of transcription. Highly conserved sequences within the promoter include the Pribnow box in bacteria and the TATA BOX in eukaryotes.COS Cells: CELL LINES derived from the CV-1 cell line by transformation with a replication origin defective mutant of SV40 VIRUS, which codes for wild type large T antigen (ANTIGENS, POLYOMAVIRUS TRANSFORMING). They are used for transfection and cloning. (The CV-1 cell line was derived from the kidney of an adult male African green monkey (CERCOPITHECUS AETHIOPS).)Stomach Ulcer: Ulceration of the GASTRIC MUCOSA due to contact with GASTRIC JUICE. It is often associated with HELICOBACTER PYLORI infection or consumption of nonsteroidal anti-inflammatory drugs (NSAIDS).Dexamethasone: An anti-inflammatory 9-fluoro-glucocorticoid.Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries.Organ Specificity: Characteristic restricted to a particular organ of the body, such as a cell type, metabolic response or expression of a particular protein or antigen.Cell Division: The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.Mitochondria: Semiautonomous, self-reproducing organelles that occur in the cytoplasm of all cells of most, but not all, eukaryotes. Each mitochondrion is surrounded by a double limiting membrane. The inner membrane is highly invaginated, and its projections are called cristae. Mitochondria are the sites of the reactions of oxidative phosphorylation, which result in the formation of ATP. They contain distinctive RIBOSOMES, transfer RNAs (RNA, TRANSFER); AMINO ACYL T RNA SYNTHETASES; and elongation and termination factors. Mitochondria depend upon genes within the nucleus of the cells in which they reside for many essential messenger RNAs (RNA, MESSENGER). Mitochondria are believed to have arisen from aerobic bacteria that established a symbiotic relationship with primitive protoeukaryotes. (King & Stansfield, A Dictionary of Genetics, 4th ed)Substrate Specificity: A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.Tissue Distribution: Accumulation of a drug or chemical substance in various organs (including those not relevant to its pharmacologic or therapeutic action). This distribution depends on the blood flow or perfusion rate of the organ, the ability of the drug to penetrate organ membranes, tissue specificity, protein binding. The distribution is usually expressed as tissue to plasma ratios.Fatty Acids, Unsaturated: FATTY ACIDS in which the carbon chain contains one or more double or triple carbon-carbon bonds.Lipoxins: Trihydroxy derivatives of eicosanoic acids. They are primarily derived from arachidonic acid, however eicosapentaenoic acid derivatives also exist. Many of them are naturally occurring mediators of immune regulation.Tumor Necrosis Factor-alpha: Serum glycoprotein produced by activated MACROPHAGES and other mammalian MONONUCLEAR LEUKOCYTES. It has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. Also known as TNF-alpha, it is only 30% homologous to TNF-beta (LYMPHOTOXIN), but they share TNF RECEPTORS.Mesenteric Arteries: Arteries which arise from the abdominal aorta and distribute to most of the intestines.Lung: Either of the pair of organs occupying the cavity of the thorax that effect the aeration of the blood.Cattle: Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor.ThiazolesAdenocarcinoma: A malignant epithelial tumor with a glandular organization.Aorta: The main trunk of the systemic arteries.Mitochondrial Proteins: Proteins encoded by the mitochondrial genome or proteins encoded by the nuclear genome that are imported to and resident in the MITOCHONDRIA.Quinacrine: An acridine derivative formerly widely used as an antimalarial but superseded by chloroquine in recent years. It has also been used as an anthelmintic and in the treatment of giardiasis and malignant effusions. It is used in cell biological experiments as an inhibitor of phospholipase A2.
Cyclooxygenase (COX) has two well-studied isoforms, called COX-1 and COX-2. COX-1 mediates the synthesis of prostaglandins ... COX-2 selective inhibitor Discovery and development of cyclooxygenase 2 inhibitors Knox, Richard (September 30, 2004), Merck ... By creating "selective" NSAIDs that inhibit COX-2, but not COX-1, the same pain relief as traditional NSAIDs is offered, but ... Complications of the COX-2 inhibitors parecoxib and valdecoxib after cardiac surgery. N Engl J Med 2005;352(11):1081-91. PMID ...
Arachidonic acid Cyclooxygenase Cyclooxygenase 2 NSAID Discovery and development of COX-2 selective inhibitors COX-2 selective ... Hla T (January 1996). "Molecular characterization of the 5.2 KB isoform of the human cyclooxygenase-1 transcript". ... In humans it is one of two cyclooxygenases. Cyclooxygenase (COX) is the central enzyme in the biosynthetic pathway to ... Prostaglandin-endoperoxide synthase (PTGS), also known as cyclooxygenase (COX), is the key enzyme in prostaglandin biosynthesis ...
... ibuprofen is a nonselective COX inhibitor, in that it inhibits two isoforms of cyclooxygenase, COX-1 and COX-2. The analgesic, ... Hippisley-Cox, J; Coupland, C (11 June 2005). "Risk of myocardial infarction in patients taking cyclo-oxygenase-2 inhibitors or ... However, the role of the individual COX isoforms in the analgesic, anti-inflammatory, and gastric damage effects of NSAIDs is ... NSAIDs such as ibuprofen work by inhibiting the cyclooxygenase (COX) enzymes, which convert arachidonic acid to prostaglandin ...
Several of these exist in multiple isoforms. Oxidation by either COX or lipoxygenase releases reactive oxygen species (ROS) and ... Competitive inhibition-DGLA and EPA compete with AA for access to the cyclooxygenase and lipoxygenase enzymes. So the presence ... Cyclooxygenases (COXs): COX-1 and COX-2 initiate the metabolism of arachidonic acid to prostanoids that contain two double ... Inhibition of COX-1 and/or the inducible COX-2 isoforms, is the hallmark of NSAIDs (non-steroidal anti-inflammatory drugs), ...
... is the third and most recently discovered cyclooxygenase (COX) isozyme, the others being COX-1 and COX-2. The COX-3 ... could be read as showing that paracetamol acts at a different site than the other NSAIDs and that more than one COX isoform ... A number of arguments counted against the COX-3 hypothesis: COX-2-selective inhibitors react weakly with the COX-3 enzymatic ... Chandrasekharan NV, Dai H, Roos KL, Evanson NK, Tomsik J, Elton TS, Simmons DL (October 2002). "COX-3, a cyclooxygenase-1 ...
Like any other selective COX-2 inhibitor ("coxib"), etoricoxib selectively inhibits isoform 2 of the enzyme cyclooxygenase (COX ... Selective COX-2 inhibitors show less activity on COX-1 compared to traditional non-steroidal anti-inflammatory drugs (NSAID). ... It has approximately 106-fold selectivity for COX-2 inhibition over COX-1. This reduces the generation of prostaglandins (PGs) ... Like all other NSAIDs the COX-2 inhibitors too have their share of adverse effects. Fixed drug eruption and generalised ...
Cyclooxygenases have two main isoforms that are called COX-1 and COX-2 (as well as a COX-3). COX-1 is responsible for the ... COX enzyme proved to be difficult to purify and was not sequenced until 1988. In 1991 the existence of the COX-2 enzyme was ... Once the COX-2 enzyme was identified, Dup-697 became the building-block for synthesis of COX-2 inhibitors. Celecoxib and ... One of the keys to developing COX-2 selective drugs is the larger active site of COX-2, which makes it possible to make ...
Cox MB, Miller CA (2002). "The p23 co-chaperone facilitates dioxin receptor signaling in a yeast model system". Toxicol. Lett. ... 2001). "Identification and characterization of novel isoforms of COP I subunits". J. Biochem. 128 (5): 793-801. doi:10.1093/ ... 2000). "Molecular identification of cytosolic prostaglandin E2 synthase that is functionally coupled with cyclooxygenase-1 in ... Wu T, Wu H, Wang J, Wang J (2011). "Expression and cellular localization of cyclooxygenases and prostaglandin E synthases in ...
A highly selective reversible inhibitor of the COX-2 isoform of cyclooxygenase, celecoxib inhibits the transformation of ... Celecoxib is approximately 10-20 times more selective for COX-2 inhibition over COX-1. It binds with its polar sulfonamide side ... Price ML, Jorgensen WL (2001). "Rationale for the observed COX-2/COX-1 selectivity of celecoxib from Monte Carlo simulations". ... The COX-2 inhibitor rofecoxib (Vioxx) was removed from the market in 2004 due to its risk. Like all NSAIDs on the US market, ...
"Impact of naproxen sodium at over-the-counter doses on cyclooxygenase isoforms in human volunteers". Int J Clin Pharmacol Ther ... and naproxen on COX-2 versus COX-1 in healthy volunteers". J Clin Pharmacol. 40 (10): 1109-20. doi:10.1177/009127000004001005 ( ... Thus, by inhibiting COX-1/2, naproxen induces an anti-inflammatory effect. Naproxen is a minor substrate of CYP1A2 and CYP2C9. ... COX-2 selective and nonselective NSAIDs have been linked to increases in the number of serious and potentially fatal ...
It inhibits COX-1, COX-2, and ALOX5 in vitro and in animal models. Flavocoxid has been approved for use as a medical food in ... Shaw KJ, Ng C, Kovacs BW (1994). "Cyclooxygenase gene expression in human endometrium and decidua". Prostaglandins Leukot. ... Ochs MJ, Suess B, Steinhilber D (2014). "5-lipoxygenase mRNA and protein isoforms". Basic & Clinical Pharmacology & Toxicology ... ALOX5 also cooperates with other lipoxygenase, cyclooxygenase, or cytochrome P450 enzymes in serial metabolic pathways to ...
Cyclooxygenase (COX) oxidation removes two C=C double bonds, leading to the TX, PG and PGI series. Lipoxygenase oxidation ... For example, PGE2 binds four receptors, dubbed EP1-4. Each is coded by a separate gene, and some exist in multiple isoforms. ... For example, cyclooxygenase action upon AA (with 4 double bonds) leads to the series-2 thromboxanes (TXA2, TXB2... ) each with ... Cyclooxygenase action on EPA (with 5 double bonds) leads to the series-3 thromboxanes (TXA3, TXB3... ) each with three double ...
An S, Yang J, So SW, Zeng L, Goetzl EJ (December 1994). "Isoforms of the EP3 subtype of human prostaglandin E2 receptor ... Abulencia JP, Gaspard R, Healy ZR, Gaarde WA, Quackenbush J, Konstantopoulos K (August 2003). "Shear-induced cyclooxygenase-2 ... COX. (PTGS). *Salicylic acids: Aloxiprin. *Aspirin (acetylsalicylic acid). *Benorilate (benorylate). *Carbasalate calcium ... "Cloning and expression of three isoforms of the human EP3 prostanoid receptor". FEBS Letters. 338 (2): 170-4. doi:10.1016/0014- ...
The enzymes cyclooxygenase-1 and -2 (i.e. prostaglandin G/H synthase 1 and 2 {PTGS1 and PTGS2}) metabolize arachidonic acid to ... γ isoforms, arachidonic acid is a key inflammatory intermediate and can also act as a vasodilator.[5] (Note separate synthetic ... "Effects of prostaglandins and COX-inhibiting drugs on skeletal muscle adaptations to exercise". J. Appl. Physiol. 115 (6): 909 ... ISBN 1-4160-2328-3.. *^ a b c d e f Walter F., PhD. Boron (2003). Medical Physiology: A Cellular And Molecular Approaoch. ...
The Arachidonic Acid then reacts with two Cyclooxygenase (COX) receptors, COX-1 and COX-2 to form Prostaglandin H2, an ... The PGF2α isoform 8-iso-PGF2α was found in significantly increased amounts in patients with endometriosis, thus being a ... Z)-7-[(1R,2R,3R,5S)-3,5-dihydroxy-2-[(E,3S)- 3-hydroxyoct-1-enyl]cyclopentyl]hept-5-enoic acid ... In small doses (1-4 mg/day), PGF2α acts to stimulate uterine muscle contractions, which aids in the birth process. However, ...
Inhibitory COX-2[edytuj , edytuj kod]. Jak wspomniano wcześniej, w polipach myszy Lkb+/- i pacjentów z PJS stwierdzono ... Suppression of Peutz-Jeghers polyposis by inhibition of cyclooxygenase-2. „Gastroenterology". 127. 4, s. 1030-7, 2004. PMID: ... Two novel mutations and a new STK11/LKB1 gene isoform in Peutz-Jeghers patients. „Hum Mutat". 20. 1, s. 78-9, 2002. DOI: ... 1, s. 38-43, 1998. DOI: 10.1038/ng0198-38. PMID: 9425897. *↑ a b c d e f g h i j k l m Hemminki A, Markie D, Tomlinson I, ...
Korbecki J, Baranowska-Bosiacka I, Gutowska I, Chlubek D (2014). "Cyclooxygenase pathways". Acta Biochimica Polonica. 61 (4): ... inhibition or stimulation of adenylyl cyclase depending on the isoform, activation of GIRK channels and activation of GRK. IP3 ... COX. (PTGS). *Salicylic acids: Aloxiprin. *Aspirin (acetylsalicylic acid). *Benorilate (benorylate). *Carbasalate calcium ... 56 (1): 12-21. doi:10.1006/geno.1998.5655. PMID 10036181.. *^ a b Ishii M, Asano K, Namkoong H, Tasaka S, Mizoguchi K, Asami T ...
PTGS2 (COX-2) is unexpressed under normal conditions in most cells, but elevated levels are found during inflammation. PTGS1 (COX-1) is constitutively expressed in many tissues and is the predominant form in gastric mucosa and in the kidneys. Inhibition of PTGS1 (COX-1) reduces the basal production of cytoprotective PGE2 and PGI2 in the stomach, which may contribute to gastric ulceration. Since PTGS2 (COX-2) is generally expressed only in cells where prostaglandins are upregulated (e.g., during inflammation), drug-candidates that selectively inhibit PTGS2 (COX-2) were suspected to show fewer side-effects[25] but proved to substantially increase risk for cardiovascular events such as heart attack and stroke. Two different mechanisms may explain contradictory effects. Low-dose aspirin protects against heart attacks and strokes by blocking ...
Cyclooxygenase 1 (COX-1), also known as prostaglandin G/H synthase 1, prostaglandin-endoperoxide synthase 1 or prostaglandin H2 synthase 1, is an enzyme that in humans is encoded by the PTGS1 gene. In humans it is one of two cyclooxygenases. Cyclooxygenase (COX) is the central enzyme in the biosynthetic pathway to prostaglandins from arachidonic acid. This protein was purified more than 20 years ago and cloned in 1988. There are two isozymes of COX encoded by distinct gene products: a constitutive COX-1 (this enzyme) and an inducible COX-2, which differ in their regulation of expression and tissue distribution. The expression of these two transcripts is differentially regulated by relevant cytokines and growth factors. This gene encodes COX-1, which ...
... (or PGE synthase) is an enzyme involved in eicosanoid and glutathione metabolism, a member of MAPEG family. It generates prostaglandin E (PGE) from prostaglandin H2. The synthase generating PGE2 is a membrane-associated protein. Humans express three prostaglandin-E synthase isozymes, each encoded by a separate gene: Jegerschold, C.; Pawelzik, S. -C.; Purhonen, P.; Bhakat, P.; Gheorghe, K. R.; Gyobu, N.; Mitsuoka, K.; Morgenstern, R.; Jakobsson, P. -J.; Hebert, H. (2008). "Structural basis for induced formation of the inflammatory mediator prostaglandin E2". Proceedings of the National Academy of Sciences. 105 (32): 11110-11115. doi:10.1073/pnas.0802894105. PMC 2516235 . PMID 18682561. Murakami M, Nakatani Y, Tanioka T, Kudo I (August 2002). "Prostaglandin E synthase". Prostaglandins Other Lipid Mediat. 68-69: 383-99. doi:10.1016/S0090-6980(02)00043-6. PMID 12432931. Park JY, Pillinger MH, Abramson SB (June 2006). "Prostaglandin E2 synthesis and secretion: the role of ...
Microsomal prostaglandin E synthase-1 (mPGES-1) or Prostaglandin E synthase is an enzyme that in humans is encoded by the PTGES gene. The protein encoded by this gene is a glutathione-dependent prostaglandin E synthase. The expression of this gene has been shown to be induced by proinflammatory cytokine interleukin 1 beta (IL1B). Its expression can also be induced by tumor suppressor protein TP53, and may be involved in TP53-induced apoptosis. Knockout studies in mice suggest that this gene may contribute to the pathogenesis of collagen-induced arthritis and mediate acute pain during inflammatory responses. Prostaglandin E synthase GRCh38: Ensembl release 89: ENSG00000148344 - Ensembl, May 2017 GRCm38: Ensembl release 89: ENSMUSG00000050737 - Ensembl, May 2017 "Human PubMed Reference:". "Mouse PubMed Reference:". Jakobsson PJ, Thorén S, Morgenstern R, et al. (1989). "Identification of human prostaglandin E synthase: a microsomal glutathione-dependent, inducible enzyme, constituting a potential ...
Both COX1 and COX2 (also termed prostaglandin-endoperoxide synthase-1 (PTGS1) and PTGS2, respectively) metabolize arachidonic acid by adding molecular O2 between carbons 9 and 11 to form an endoperoxide bridge between these two carbons, adding molecular O2 to carbon 15 to yield a 15-hydroperoxy product, creating a carbon-carbon bond between carbons 8 and 12 to create a cyclopentane ring in the middle of the fatty acid, and in the process making PGG2, a product that has two fewer double bonds than arachidonic acid. The 15-hydroperoxy residue of PGG2 is then reduced to a 15-hydroxyl residue thereby forming PGH2. PGH2 is the parent prostanoid to all other prostanoids. It is metabolized by (see diagram in Prostanoids: a) the Prostaglandin E synthase pathway in which any one of three isozymes, PTGES, PTGES2, or PTGES3, convert PGH2 to PGE2 (subsequent products of this pathway include PGA2 and PGB2 (see Prostanoid#Biosynthesis); b) PGF synthase ...
Most NSAIDs act as nonselective inhibitors of the enzyme cyclooxygenase (COX), inhibiting both the cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) isoenzymes. This inhibition is competitively reversible (albeit at varying degrees of reversibility), as opposed to the mechanism of aspirin, which is irreversible inhibition.[79] COX catalyzes the formation of prostaglandins and thromboxane from arachidonic acid (itself derived from the cellular phospholipid bilayer by phospholipase A2). Prostaglandins act (among other things) as messenger molecules in the process of inflammation. This mechanism of action was elucidated by John Vane (1927-2004), who received a Nobel Prize for his work (see Mechanism of action of aspirin). COX-1 is a constitutively expressed enzyme with a "house-keeping" ...
... s are a subclass of eicosanoids consisting of the prostaglandins (mediators of inflammatory and anaphylactic reactions), the thromboxanes (mediators of vasoconstriction), and the prostacyclins (active in the resolution phase of inflammation.) Prostaglandin H2 PGD synthase PGD2 PGJ2 PGE synthase PGE2 PGA2 PGB2 Prostacyclin synthase PGI2 6-keto-PGFα PGE 9- ketoreductase PGF2 Thromboxane-A synthase TXA2 Cyclooxygenase (COX) catalyzes the conversion of the free essential fatty acids to prostanoids by a two-step process. In the first step, two molecules of O2 are added as two peroxide linkages and a 5-member carbon ring is forged near the middle of the fatty acid chain. This forms the short-lived, unstable intermediate Prostaglandin G (PGG). One of the peroxide linkages sheds a single oxygen, forming PGH. (See diagrams and more detail at Cyclooxygenase). All other prostanoids originate from PGH (as PGH1, PGH2, or PGH3). The image at right ...
... is an antiinflammatory agent. More specifically, it is a nonsteroidal anti-inflammatory drug (NSAID) that acts via inhibition of the enzyme cyclooxygenase (COX). Wiseman, E. H.; McIlhenny, H. M.; Bettis, J. W. (1975). "Flumizole, a new nonsteroidal anti-inflammatory agent". Journal of pharmaceutical sciences. 64 (9): 1469-1475. doi:10.1002/jps.2600640909. PMID 810570 ...
Selective COX-2 inhibitors are a type of nonsteroidal anti-inflammatory drug (NSAID) that directly targets cyclooxygenase-2, COX-2, an enzyme responsible for inflammation and pain. Targeting selectivity for COX-2 reduces the risk of peptic ulceration, and is the main feature of celecoxib, rofecoxib and other members of this drug class. After several COX-2 inhibiting drugs were approved for marketing, data from clinical trials revealed that COX-2 inhibitors caused a significant increase in heart attacks and strokes, with some drugs in the class having worse risks than others. Rofecoxib (commonly known as Vioxx) was taken off the market in 2004 because of these concerns and celecoxib and ...
Интерлеукин 17A је протеин који је код људи кодиран IL17A геном.[1][2][3] Протеин кодиран овим геном је проинфламаторни цитокин произведен активираним Т ћелијама.[4] Овај цитокин регулише активности НФ-капаБ и митоген активираних протеин киназа. Овај цитокин може да стимулише изражавање ИЛ-6 и циклооксигеназе-2 (PTGS2/COX-2), као и да појача продукцију нитрик оксида (NO). Високи нивои овог цитокина су асоцирани са неколико хроничних инфламаторних обољења укључујући реуматоидни артритис, псоријазу и мултиплу склерозу.[2] ...
Cyclooxygenase 1 (COX-1), also known as prostaglandin G/H synthase 1, prostaglandin-endoperoxide synthase 1 or prostaglandin H2 synthase 1, is an enzyme that in humans is encoded by the PTGS1 gene. In humans it is one of two cyclooxygenases. Cyclooxygenase (COX) is the central enzyme in the biosynthetic pathway to prostaglandins from arachidonic acid. This protein was purified more than 20 years ago and cloned in 1988. There are two isozymes of COX encoded by distinct gene products: a constitutive COX-1 (this enzyme) and an inducible COX-2, which differ in their regulation of expression and tissue distribution. The expression of these two transcripts is differentially regulated by relevant cytokines and growth factors. This gene encodes COX-1, which ...
PTGS2 (COX-2) is unexpressed under normal conditions in most cells, but elevated levels are found during inflammation. PTGS1 (COX-1) is constitutively expressed in many tissues and is the predominant form in gastric mucosa and in the kidneys. Inhibition of PTGS1 (COX-1) reduces the basal production of cytoprotective PGE2 and PGI2 in the stomach, which may contribute to gastric ulceration. Since PTGS2 (COX-2) is generally expressed only in cells where prostaglandins are upregulated (e.g., during inflammation), drug-candidates that selectively inhibit PTGS2 (COX-2) were suspected to show fewer side-effects[25] but proved to substantially increase risk for cardiovascular events such as heart attack and stroke. Two different mechanisms may explain contradictory effects. Low-dose aspirin protects against heart attacks and strokes by blocking ...
Интерлеукин 17A је протеин који је код људи кодиран IL17A геном.[1][2][3] Протеин кодиран овим геном је проинфламаторни цитокин произведен активираним Т ћелијама.[4] Овај цитокин регулише активности НФ-капаБ и митоген активираних протеин киназа. Овај цитокин може да стимулише изражавање ИЛ-6 и циклооксигеназе-2 (PTGS2/COX-2), као и да појача продукцију нитрик оксида (NO). Високи нивои овог цитокина су асоцирани са неколико хроничних инфламаторних обољења укључујући реуматоидни артритис, псоријазу и мултиплу склерозу.[2] ...
The two COX isoforms appear to play different roles in neuroinflammation. COX-1 (inhibited only by traditional NSAIDs such as ... cyclooxygenase-2 [COX-2] inhibitors like celecoxib and rofecoxib, salicylates [aspirin]) and risk of either Alzheimer disease ( ... COX-2, but not COX-1, activity is necessary for the induction of perforant path long-term potentiation and spatial learning in ... COX-2 (inhibited by the selective COX-2 inhibitors like celecoxib and rofecoxib, as well as by traditional NSAIDs) is expressed ...
The anti-inflammatory effects of 1,8â cineole (eucalyptol) in the treatment of acute bronchitis and treatment of chronic airway ... There are two isoforms of cyclooxygenase: COX?1 is an essential enzyme that is present in many body tissues and regulates the ... 2 isoforms of cyclooxygenase were measured with Standard Kit (Cayman Chemical, USA). COX activity assay is a colorimetrical ... 8-cineole on the activity of cyclooxygenase and its two isoforms (COX1 and COX‑2) were analysed and compared with the effects ...
COX activation contributes undetectably to lipid peroxidation induced by LPS; and (c) COX-2, but not COX-1, contributes to the ... Nonselective inhibition of both COX isoforms completely inhibits PGI-M excretion. (c) The effect of LPS on PGI-M excretion ... To examine the role of cyclooxygenase (COX) isozymes in prostaglandin formation and oxidant stress in inflammation, we ... Effect of regulated expression of human cyclooxygenase isoforms on eicosanoid and isoeicosanoid production in inflammation.. ...
... colloquially known as cyclooxygenase (COX; ref. 3). Mammalian cells contain two isoforms of COX (2-4). They are structurally ... However, we have previously shown that this particular iP may also be formed by either COX isoform in vitro (31, 45). COX ... Systemic biosynthesis of prostacyclin by cyclooxygenase (COX)-2: the human pharmacology of a selective inhibitor of COX-2. Proc ... However, given this caveat, inhibition of both COX isoforms with ibuprofen or COX-2 inhibition with celecoxib abolished the ...
Cyclooxygenase (COX) has two well-studied isoforms, called COX-1 and COX-2. COX-1 mediates the synthesis of prostaglandins ... COX-2 selective inhibitor Discovery and development of cyclooxygenase 2 inhibitors Knox, Richard (September 30, 2004), Merck ... By creating "selective" NSAIDs that inhibit COX-2, but not COX-1, the same pain relief as traditional NSAIDs is offered, but ... Complications of the COX-2 inhibitors parecoxib and valdecoxib after cardiac surgery. N Engl J Med 2005;352(11):1081-91. PMID ...
Two isoforms of this enzyme have been identified; cyclooxygenase (COX) 1 and COX-2. The present study was undertaken to ... Furthermore, COX-2 expression seems to be increased in a subset of adenomas. COX-2 may provide an attractive therapeutic target ... COX-2, but not COX-1, gene expression is markedly elevated in most human colorectal cancers compared with accompanying normal ... Because COX-2 expression is low to undetectable in normal colorectal mucosa, 14 unpaired adenomas were examined for COX-2 ...
Cyclooxygenase-2-dependent prostacyclin formation and blood pressure homeostasis: targeted exchange of cyclooxygenase isoforms ... Deletion of COX-2 completely inhibited COX-2 protein expression without influencing the expression of COX-1 or of IP receptor ... The physiological relevance of COX-2 in arterial thrombosis was studied in COX-2KO mice. To assess the effect of COX-2 deletion ... suppressed TF activity in carotid artery rings from COX-2KO mice (COX-2KO, 588.18±73.0 7 U/μg protein versus COX-2KO+CAY10591, ...
To date, which COX isoform (COX-1 or COX-2) plays a more important role in during fetal development and influences kidney ... function early in life is not known, though evidence points to a predominant role for COX-2. Clinical implications of the use ... 2. COX Isoforms. Two main COX isoforms have been identified constitutive COX-1 and inducible COX-2, which catalyze the first ... abundantly express both COX isoforms. The most recently discovered isoform, COX-3, is believed to be a splice variant of COX-1 ...
Two COX isoforms have been identified; first, as a constitutive form (COX-1), which is thought to have an important ... An attack may last for 48 hours, and damage to the Cyclooxygenase-2 (COX-2), a widely distributed enzyme, plays an important ... The initiation of prostanoid synthesis from arachidonic acid involves the enzyme cyclooxygenase (COX), an enzyme that is also ... pancreatic COX-2 mRNA levels rose within 15 minutes of the start of cerulein administration and that pancreatic COX-2 protein ...
Cyclooxygenase has two isoforms, i.e., COX-1 and COX-2. COX-1 is constitutively expressed in most tissues and is thought to be ... COX-2-negative; b, case 13: breast cancer, COX-2-positive; c, case 6: lung cancer, COX-2-positive; d, case 11: colon cancer, ... Cyclooxygenase expression was determined by Western blot analyses. B, effects of TGFβ (5 ng/mL) on COX-2 expression in primary ... Cyclooxygenase (COX) is a rate-limiting enzyme of prostaglandin synthesis in the arachidonic acid cascade ( 1, 2). ...
COX), a key enzyme in the conversion of arachidonic acid to prostaglandins. Two isoforms of COX have been characterized, COX-1 ... Two isoforms for COX have been described, COX-1 and COX-2. We and others have shown that COX-2 levels are markedly increased in ... COX-2 Expression and Prostaglandin Production.. The COX-2 transfected Caco-2 cells exhibited a 10- to 12-fold increase in COX-2 ... Two COX isoforms have been characterized, COX-1 and COX-2. COX-1 is expressed in normal intestine, but its levels do not change ...
There are two cyclooxygenase isoforms, COX-1 and COX-2. COX-1 is produced constitutively in most cell types, whereas COX-2 is ... The expression of COX-2 protein was assessed by western blot and analysed by densitometry compared to β-actin expression. COX-2 ... A. Tomlinson, I. Appleton, A. R. Moore et al., "Cyclo-oxygenase and nitric oxide synthase isoforms in rat carrageenin-induced ... The Effect of LPS on COX-2, PGE2 and PGD2 Expression in Lung Fibroblasts. To determine the dynamic expression of COX-2 in rat ...
Cyclooxygenases have two main isoforms that are called COX-1 and COX-2 (as well as a COX-3). COX-1 is responsible for the ... COX enzyme proved to be difficult to purify and was not sequenced until 1988. In 1991 the existence of the COX-2 enzyme was ... Once the COX-2 enzyme was identified, Dup-697 became the building-block for synthesis of COX-2 inhibitors. Celecoxib and ... One of the keys to developing COX-2 selective drugs is the larger active site of COX-2, which makes it possible to make ...
Four of the tested compounds proved to be good inhibitors of both COX isoforms, but only compound A3 showed a good COX-2 ... In an effort to obtain safer NSAIDs, we assessed the direct cyclooxygenase (COX) inhibition activity and we investigated the ... The in vitro COX inhibition assays were performed against ovine COX-1 and human recombinant COX-2. Molecular docking studies ... The present data prove that the investigated compounds inhibit COX and thus confirm the previously reported in vivo anti- ...
Staining for the inducible COX-2 isoform of the same LPS-challenged mice was not qualitatively affected by COX-1 deficiency ( ... has been suggested to represent a distinct isoform, COX-3. In rodents and humans, however, COX-3 encodes proteins whose amino ... 2005) Cyclooxygenase 2 (COX-2) inhibition increases the inflammatory response in the brain during systemic immune stimuli. J ... 2002) COX-3, a cyclooxygenase-1 variant inhibited by acetaminophen and other analgesic/antipyretic drugs: cloning, structure, ...
... and COX-2. Aspirin impairs the biosynthesis of all prostanoids through the irreversible inhibition of both COX isoforms. Long- ... Prostanoids are a large family of bioactive lipids derived from the activity of cyclooxygenase-1 (COX-1) ... but the COX isoform, downstream prostanoid, and cell compartment responsible for this effect are yet to be determined. Here, we ... 8) or COX-1+/+ platelets isolated from donor mice pretreated with vehicle, aspirin, SC-560, NS-398, or picotamide (. n. = 10, 9 ...
... and COX-2. Aspirin impairs the biosynthesis of all prostanoids through the irreversible inhibition of both COX isoforms. Long- ... Prostanoids are a large family of bioactive lipids derived from the activity of cyclooxygenase-1 (COX-1) ... but the COX isoform, downstream prostanoid, and cell compartment responsible for this effect are yet to be determined. Here, we ... Inhibition of the COX-1/TXA2 pathway in platelets decreased aggregation of platelets on tumor cells, endothelial activation, ...
COX-2, Interleukin-lβ, Interleukin-6, α, HLE, and iNOS. Methods and compositions for treating and preventing diseases, i ... and Cyclooxygenase-2 (COX-2) was measured. Specifically, the IC50 values were measured on isolated enzymes for COX-1 and COX-2 ... Inhibiting the inducible isoform of nitric oxide (iNOS) also exhibits clinical benefits. Nitric Oxide (NO ) plays a critical ... The synthesis of all but the leukotrienes involves the enzyme cyclooxygenase (COX); the synthesis of leukotrienes involves the ...
COX), thereby blocking the synthesis of prostaglandins. Cyclooxygenase exists in at least two different isoforms COX-1 and COX- ... A major change in the use of NSAIDs occurred with the discovery of COX-2 inhibitors. In the beginning it was thought that COX- ... More reports on safety have to come for the complete acceptance of COX- 2 inhibitors. Therefore older COX-1 NSAIDs are still in ... These COX-2 inhibitors are contraindicated in kidney dysfunction and congestive heart failure where the extent of effect is ...
Two COX isoforms have been cloned: COX-1 and COX-2. COX-1 is constitutively expressed in most mammalian cells and is ... Expression of cyclooxygenase-2 (COX-2) in human invasive transitional cell carcinoma (TCC) of the urinary bladder. Cancer Res ... The expression and enzymatic activities of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) as well as the ... The COX-2 results are not surprising in that we have reported that COX-2 overexpression is an early event in rat esophageal ...
Cox 2 Inhibitors:. - highly selective cyclooxygenase-2 (COX-2) inhibitors have no effect on platelet aggregation and bleeding ... non steroidals exert their actions by inhibiting isoforms of cyclo-oxygenase 1 and 2;. - cox 1: expressed in the stomach and ... cox 2:. - cox 2 receptor is not normally expressed in synovial tissue;. - regulates inflammatory response and is responsible ... Nonaspirin NSAIDs, Cyclooxygenase 2 Inhibitors, and the Risk for Stroke.. - Risk of hospitalization for myocardial infarction ...
There are two known isoforms of cyclo-oxygenase, COX-1 and COX-2 [56]. COX-1 is constitutively expressed in most tissues and ... They act through the inhibition of the two known isoforms of cyclo-oxygenase (COX-1, COX-2), the key enzyme in the metabolism ... In recent years, the development of COX-2-selective inhibitors, which inhibit COX-2 but not COX-1 at therapeutic doses, has ... COX-2 technology-a new approach to pain management. The mechanism of action of NSAIDs is related to the inhibition of cyclo- ...
Two COX isoforms have been identified as COX-1 and COX-2. COX-1 is expressed constitutively in several cell types of normal ... Cyclooxygenase-2 (COX-2) and the inflammogenesis of cancer. Subcell Biochem 2007;42:3-126. ... May cyclooxygenase-2 (COX-2), p21 and p27 expression affect prognosis and therapeutic strategy of patients with malignant ... Cyclooxygenases. Cyclooxygenases, also known as prostaglandin-endoperoxide synthases, are key regulatory enzymes in the ...
In the early 1990s, COX was demonstrated to exist as two distinct isoforms. COX-1 is constitutively expressed as a " ... COX. cyclooxygenase. NF-κB. nuclear factor-κB. POAG. primary open angle glaucoma. CLASS. Celecoxib Long-Term Arthritis Safety ... The enzyme cyclooxygenase (COX) catalyzes the first step of the synthesis of prostanoids. ... Cyclooxygenase-2-10 Years Later Message Subject (Your Name) has forwarded a page to you from Journal of Pharmacology and ...
Two isoforms exist: COX-1 and COX-2. COX-2 is considered the inducible isoform. Its expression is increased by a number of ... 3 increased formation of cyclooxygenase (COX)-dependent vasoconstrictors,4 but also to increased expression of the most potent ... COX-2, Another Important Player in the Nitric Oxide-Endothelin Cross-Talk. Good News for COX-2 Inhibitors?. Ulrich Hink, Thomas ... Further evidence for a role of COX-2 was provided by Western blot analysis demonstrating that COX-2 expression was found to be ...
  • Inhibition of the COX-1/TXA2 pathway in platelets decreased aggregation of platelets on tumor cells, endothelial activation, tumor cell adhesion to the endothelium, and recruitment of metastasis-promoting monocytes/macrophages, and diminished the formation of a premetastatic niche. (jci.org)
  • Thus, platelet-derived TXA2 orchestrates the generation of a favorable intravascular metastatic niche that promotes tumor cell seeding and identifies COX-1/TXA2 signaling as a target for the prevention of metastasis. (jci.org)
  • E and F ) Number of tumor cells ( E ) and representative tile scans ( F ) of the left lung from platelet-depleted recipient mice ( n = 5) at 1 day after i.v. injection of platelets (from COX-1 -/- or COX-1 +/+ donor mice) and tumor cells (B16F10-CMFDA cells, white). (jci.org)
  • These results suggest a novel tumor suppressive role of BRB through inhibition of COX-2, iNOS, and c- Jun . (aacrjournals.org)
  • We compared the angiogenic characteristics of a COX-2-positive human pancreatic tumor cell line, BxPC-3, with those of a COX-2-negative pancreatic tumor cell line, AsPC-1. (aacrjournals.org)
  • These results suggest an involvement of COX-2 in the control of tumor-dependent angiogenesis and growth in certain pancreatic cancers and provide the rational for inhibition of the COX pathway as an effective therapeutic approach for pancreatic tumors. (aacrjournals.org)
  • One of the mechanisms by which COX-2 supports tumorigenesis is by stimulating angiogenesis, the formation of new blood vessels from existing vasculature, a crucial process for tumor growth and expansion ( 17 , 18 ). (aacrjournals.org)
  • Thus, tumor growth is markedly reduced in COX-2 (−/−) mice compared with wild-type or COX-1 (−/−) animals ( 19 ). (aacrjournals.org)
  • In the present study, we compared COX-2-positive and COX-2-negative pancreatic tumor cell lines to evaluate the involvement of the COX-2 pathway in angiogenesis and growth of pancreatic cancer. (aacrjournals.org)
  • Whereas COX-2 and PGE 2 are associated with cancer cell survival and tumor angiogenesis, arachidonic acid itself is a strong apoptotic signal that may facilitate cancer cell death. (aacrjournals.org)
  • To further elucidate the mechanism responsible for increased levels of PGE 2 in colorectal tumors, we determined the amounts of mPGES and COX-2 in 18 paired samples (tumor and adjacent normal) of colorectal cancer. (aacrjournals.org)
  • Tumor necrosis factor-α induced both mPGES and COX-2, but the time course and magnitude of induction differed. (aacrjournals.org)
  • In this study, we aimed to investigate the associations between COX-2, PGE 2 and NO in co-cultures of human colon cancer spheroids obtained from different tumor grades with normal human colonic epithelium and myofibroblast monolayers. (springer.com)
  • COX-2, PGE 2 and NO levels depended on the tumor grade of the cells, being the highest in Duke's stage III colon carcinoma. (springer.com)
  • Summing up, we showed that addition of L-arginine at doses which did not stimulate NO level caused a significant decrease in COX-2 and PGE 2 amounts in co-cultures of colon tumor spheroids with normal epithelial cells and myofibroblasts. (springer.com)
  • Therefore, selective inhibitors of COX-2 may also block PGE 2 generation minimizing its colorectal-tumor-promoting effects. (springer.com)
  • Selective inhibition of COX-2 and PGE 2 production and influencing NO synthesis in the tumor microenvironment may represent important goals for prevention or therapy of colon cancers. (springer.com)
  • 2001), and is highly expressed in a variety of human cancers and cancer cell lines (Liao and Milas 2004).COX-2 overexpression is associated with more aggressive biological tumor behaviors (Liao and Milas 2004), and the inhibition of COX-2 has been regarded as an effective anticancer strategy (Davies et al. (thefreelibrary.com)
  • An elevated expression of COX-2 as the inducible form of the cyclooxygenases was detected in 36% of tumors and was significantly associated with several clinicopathological parameters, for example positive nodal status, poor differentiation and larger tumor size. (hu-berlin.de)
  • In contrast, an increased expression of COX-1 was detected in 45% of breast carcinomas and was associated with smaller tumor size and negative nodal status. (hu-berlin.de)
  • FLP inhibited tumor growth and metastasis in a Lewis lung xenograft mice model through the Cox-2 pathway. (biomedcentral.com)
  • Together, PGs comprise a diverse family of biologically active lipids derived from the enzymatic conversion of arachidonic acid by COX to PGG 2 /H 2 followed by the generation of five primary bioactive prostanoids PGE 2 , PGI 2 , PGD 2 , PGF 2α and thromboxane A 2 [ 4 , 5 , 6 ]. (mdpi.com)
  • COX is a key enzyme in catalyzing the conversion of arachidonic acid, which is released from the cell membrane, to prostaglandin (PG) G 2 and H 2 . (aspetjournals.org)
  • Rather, ascorbic acid dose-dependently (0.1-100 microM) produced a significant reduction in IL-1beta-mediated production of 8-iso-prostaglandin F2alpha (8-iso-PGF2alpha), a reliable indicator of free radical formation, suggesting that the effects of ascorbic acid on COX-2-mediated PGE2 biosynthesis may be the result of the maintenance of the neuronal redox status since COX activity is known to be enhanced by oxidative stress. (cogprints.org)
  • Our results provide in vitro evidence that the neuroprotective effects of ascorbic acid may depend, at least in part, on its ability to reduce neuronal COX-2 activity and PGE2 synthesis, owing to its antioxidant properties. (cogprints.org)
  • These findings support an involvement of COX-1 in bidirectional interplay between ECs and PVCs in initiating vascular PGE 2 and downstream HPA response to proinflammatory challenges. (jneurosci.org)
  • These results suggest that bone-derived TGFβ up-regulates COX-2 expression in breast cancer cells, thereby increasing prostaglandin E 2 production, which in turn, stimulates osteoclastic bone destruction, leading to the progression of bone metastases. (aacrjournals.org)
  • Recently COX-2 has been reported to frequently overexpress in colorectal neoplasms and to play a role in colorectal tumorigenesis and tumour progression. (nih.gov)
  • These findings, coupled with recent evidence demonstrating the benefits of COX-2 inhibitors in many cancer models, underscore the significance of aberrant COX-2 expression and suggest that pharmacologic inhibition of COX-2 and/or regulation of its expression may limit cancer progression. (rupress.org)
  • Although no prenatal or postnatal phenotype involving the DA was originally reported in either COX-deficient line, functional compensation of one isoform for the other may have obscured a neonatal DA phenotype. (pnas.org)
  • The current study aims to resolve the functional significance of COX-2 in human gastric ulcer from a biological and clinical perspective. (clinicaltrials.gov)
  • Molecular docking studies were performed to explain the possible interactions between the inhibitors and both COX isoforms binding pockets. (mdpi.com)
  • These and other explanations offered ( 1 )( 2 )( 3 )( 4 )( 5 ) have not been generally accepted because of the lack of molecular evidence in vivo and the high concentrations of ω-3 PUFA required to achieve putative "beneficial actions" in vitro. (rupress.org)