Phospholipase D: An enzyme found mostly in plant tissue. It hydrolyzes glycerophosphatidates with the formation of a phosphatidic acid and a nitrogenous base such as choline. This enzyme also catalyzes transphosphatidylation reactions. EC 3.1.4.4.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.Phospholipases A2: Phospholipases that hydrolyze the acyl group attached to the 2-position of PHOSPHOGLYCERIDES.Phospholipases A: Phospholipases that hydrolyze one of the acyl groups of phosphoglycerides or glycerophosphatidates.Type C Phospholipases: A subclass of phospholipases that hydrolyze the phosphoester bond found in the third position of GLYCEROPHOSPHOLIPIDS. Although the singular term phospholipase C specifically refers to an enzyme that catalyzes the hydrolysis of PHOSPHATIDYLCHOLINE (EC 3.1.4.3), it is commonly used in the literature to refer to broad variety of enzymes that specifically catalyze the hydrolysis of PHOSPHATIDYLINOSITOLS.Phospholipases: A class of enzymes that catalyze the hydrolysis of phosphoglycerides or glycerophosphatidates. EC 3.1.-.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.Phospholipase C gamma: A phosphoinositide phospholipase C subtype that is primarily regulated by PROTEIN-TYROSINE KINASES. It is structurally related to PHOSPHOLIPASE C DELTA with the addition of SRC HOMOLOGY DOMAINS and pleckstrin homology domains located between two halves of the CATALYTIC DOMAIN.Cell Membrane: The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.Phosphoinositide Phospholipase C: A type C phospholipase with specificity towards PHOSPHATIDYLINOSITOLS that contain INOSITOL 1,4,5-TRISPHOSPHATE. Many of the enzymes listed under this classification are involved in intracellular signaling.Phospholipase C beta: A phosphoinositide phospholipase C subtype that is primarily regulated by its association with HETEROTRIMERIC G-PROTEINS. It is structurally related to PHOSPHOLIPASE C DELTA with the addition of C-terminal extension of 400 residues.Prostaglandins F: (9 alpha,11 alpha,13E,15S)-9,11,15-Trihydroxyprost-13-en-1-oic acid (PGF(1 alpha)); (5Z,9 alpha,11,alpha,13E,15S)-9,11,15-trihydroxyprosta-5,13-dien-1-oic acid (PGF(2 alpha)); (5Z,9 alpha,11 alpha,13E,15S,17Z)-9,11,15-trihydroxyprosta-5,13,17-trien-1-oic acid (PGF(3 alpha)). A family of prostaglandins that includes three of the six naturally occurring prostaglandins. All naturally occurring PGF have an alpha configuration at the 9-carbon position. They stimulate uterine and bronchial smooth muscle and are often used as oxytocics.Phospholipase A2 Inhibitors: Compounds that inhibit or block the activity of a PHOSPHOLIPASE A2 enzyme.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.Membranes: Thin layers of tissue which cover parts of the body, separate adjacent cavities, or connect adjacent structures.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.Intracellular Membranes: Thin structures that encapsulate subcellular structures or ORGANELLES in EUKARYOTIC CELLS. They include a variety of membranes associated with the CELL NUCLEUS; the MITOCHONDRIA; the GOLGI APPARATUS; the ENDOPLASMIC RETICULUM; LYSOSOMES; PLASTIDS; and VACUOLES.Membrane Lipids: Lipids, predominantly phospholipids, cholesterol and small amounts of glycolipids found in membranes including cellular and intracellular membranes. These lipids may be arranged in bilayers in the membranes with integral proteins between the layers and peripheral proteins attached to the outside. Membrane lipids are required for active transport, several enzymatic activities and membrane formation.Phospholipases A1: A phospholipase that hydrolyzes the acyl group attached to the 1-position of PHOSPHOGLYCERIDES.Prostaglandins A: (13E,15S)-15-Hydroxy-9-oxoprosta-10,13-dien-1-oic acid (PGA(1)); (5Z,13E,15S)-15-hydroxy-9-oxoprosta-5,10,13-trien-1-oic acid (PGA(2)); (5Z,13E,15S,17Z)-15-hydroxy-9-oxoprosta-5,10,13,17-tetraen-1-oic acid (PGA(3)). A group of naturally occurring secondary prostaglandins derived from PGE; PGA(1) and PGA(2) as well as their 19-hydroxy derivatives are found in many organs and tissues.Phospholipase C delta: A phosphoinositide phospholipase C subtype that is structurally defined by the presence of an N-terminal pleckstrin-homology and EF-hand domains, a central catalytic domain, and a C-terminal calcium-dependent membrane-binding domain.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.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.Isoenzymes: Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.Group IV Phospholipases A2: A cytosolic phospholipase A2 group that plays an important role in the release of free ARACHIDONIC ACID, which in turn is metabolized to PROSTAGLANDINS by the CYCLOOXYGENASE pathway and to LEUKOTRIENES by the 5-LIPOXYGENASE pathway.Receptors, Phospholipase A2: Cell surface receptors that bind to and internalize SECRETED PHOSPHOLIPASES A2. Although primarily acting as scavenger receptors, these proteins may also play a role in intracellular signaling. Soluble forms of phospholipase A2 receptors occur through the action of proteases and may a play a role in the inhibition of extracellular phospholipase activity.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.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).Prostaglandin Antagonists: Compounds that inhibit the action of prostaglandins.Group II Phospholipases A2: A subcategory of secreted phospholipases A2 that includes enzymes isolated from a variety of sources. The creation of this group is based upon similarities in the structural determinants of the enzymes including a negatively charged carboxy-terminal segment.Phosphatidylinositol Diacylglycerol-Lyase: A phosphorus-oxygen lyase found primarily in BACTERIA. The enzyme catalyzes the cleavage of a phosphoester linkage in 1-phosphatidyl-1D-myo-inositol to form 1D-myo-inositol 1,2-cyclic phosphate and diacylglycerol. The enzyme was formerly classified as a phosphoric diester hydrolase (EC 3.1.4.10) and is often referred to as a TYPE C PHOSPHOLIPASES. However it is now known that a cyclic phosphate is the final product of this enzyme and that water does not enter into the reaction.Phosphatidic Acids: Fatty acid derivatives of glycerophosphates. They are composed of glycerol bound in ester linkage with 1 mole of phosphoric acid at the terminal 3-hydroxyl group and with 2 moles of fatty acids at the other two hydroxyl groups.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.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.Kinetics: The rate dynamics in chemical or physical systems.Prostaglandins D: Physiologically active prostaglandins found in many tissues and organs. They show pressor activity, are mediators of inflammation, and have potential antithrombotic effects.Membrane Potentials: The voltage differences across a membrane. For cellular membranes they are computed by subtracting the voltage measured outside the membrane from the voltage measured inside the membrane. They result from differences of inside versus outside concentration of potassium, sodium, chloride, and other ions across cells' or ORGANELLES membranes. For excitable cells, the resting membrane potentials range between -30 and -100 millivolts. Physical, chemical, or electrical stimuli can make a membrane potential more negative (hyperpolarization), or less negative (depolarization).Cell Line: Established cell cultures that have the potential to propagate indefinitely.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.Phosphatidylinositols: Derivatives of phosphatidic acids in which the phosphoric acid is bound in ester linkage to the hexahydroxy alcohol, myo-inositol. Complete hydrolysis yields 1 mole of glycerol, phosphoric acid, myo-inositol, and 2 moles of fatty acids.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.Prostaglandin-Endoperoxide Synthases: Enzyme complexes that catalyze the formation of PROSTAGLANDINS from the appropriate unsaturated FATTY ACIDS, molecular OXYGEN, and a reduced acceptor.Arachidonic AcidsMembranes, Artificial: Artificially produced membranes, such as semipermeable membranes used in artificial kidney dialysis (RENAL DIALYSIS), monomolecular and bimolecular membranes used as models to simulate biological CELL MEMBRANES. These membranes are also used in the process of GUIDED TISSUE REGENERATION.Phospholipases A2, Secretory: A subcategory of phospholipases A2 that are secreted from cells. They are 14 kDa proteins containing multiple disulfide-bonds and access their substrate via an interfacial binding site that interacts with phospholipid membranes. In addition specific PHOSPHOLIPASE A2 RECEPTORS can bind to and internalize the enzymes.Erythrocyte Membrane: The semi-permeable outer structure of a red blood cell. It is known as a red cell 'ghost' after HEMOLYSIS.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.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.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.Cytosol: Intracellular fluid from the cytoplasm after removal of ORGANELLES and other insoluble cytoplasmic components.Lysophospholipase: An enzyme that catalyzes the hydrolysis of a single fatty acid ester bond in lysoglycerophosphatidates with the formation of glyceryl phosphatidates and a fatty acid. EC 3.1.1.5.Alprostadil: A potent vasodilator agent that increases peripheral blood flow.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.Estrenes: Unsaturated derivatives of the ESTRANES with methyl groups at carbon-13, with no carbon at carbon-10, and with no more than one carbon at carbon-17. They must contain one or more double bonds.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.Phosphatidylcholines: Derivatives of phosphatidic acids in which the phosphoric acid is bound in ester linkage to a choline moiety. Complete hydrolysis yields 1 mole of glycerol, phosphoric acid and choline and 2 moles of fatty acids.Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water.DiglyceridesMembrane 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.Group VI Phospholipases A2: A calcium-independent phospholipase A2 group that may play a role in membrane phospholipid remodeling and homeostasis by controling the levels of PHOSPHATIDYLCHOLINE in mammalian cell membranes.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.Phospholipids: Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides see GLYCEROPHOSPHOLIPIDS) or sphingosine (SPHINGOLIPIDS). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system.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.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.Glycerophospholipids: 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.Prostaglandins, Synthetic: Compounds obtained by chemical synthesis that are analogs or derivatives of naturally occurring prostaglandins and that have similar activity.Pyrrolidinones: A group of compounds that are derivatives of oxo-pyrrolidines. A member of this group is 2-oxo pyrrolidine, which is an intermediate in the manufacture of polyvinylpyrrolidone. (From Merck Index, 11th ed)Solubility: The ability of a substance to be dissolved, i.e. to form a solution with another substance. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed)Membrane Fluidity: The motion of phospholipid molecules within the lipid bilayer, dependent on the classes of phospholipids present, their fatty acid composition and degree of unsaturation of the acyl chains, the cholesterol concentration, and temperature.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.Cell Membrane Permeability: A quality of cell membranes which permits the passage of solvents and solutes into and out of cells.Prostaglandins E, Synthetic: Analogs or derivatives of prostaglandins E that do not occur naturally in the body. They do not include the product of the chemical synthesis of hormonal PGE.Inositol Phosphates: Phosphoric acid esters of inositol. They include mono- and polyphosphoric acid esters, with the exception of inositol hexaphosphate which is PHYTIC ACID.Phosphatidylinositol 4,5-Diphosphate: A phosphoinositide present in all eukaryotic cells, particularly in the plasma membrane. It is the major substrate for receptor-stimulated phosphoinositidase C, with the consequent formation of inositol 1,4,5-triphosphate and diacylglycerol, and probably also for receptor-stimulated inositol phospholipid 3-kinase. (Kendrew, The Encyclopedia of Molecular Biology, 1994)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.1-Butanol: A four carbon linear hydrocarbon that has a hydroxy group at position 1.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.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.Electrophoresis, Polyacrylamide Gel: Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.Lysophosphatidylcholines: Derivatives of PHOSPHATIDYLCHOLINES obtained by their partial hydrolysis which removes one of the fatty acid moieties.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Molecular Weight: The sum of the weight of all the atoms in a molecule.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.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Phospholipases A2, Cytosolic: A subcategory of phospholipases A2 that occur in the CYTOSOL.GTP-Binding Proteins: Regulatory proteins that act as molecular switches. They control a wide range of biological processes including: receptor signaling, intracellular signal transduction pathways, and protein synthesis. Their activity is regulated by factors that control their ability to bind to and hydrolyze GTP to GDP. EC 3.6.1.-.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.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.Substrate Specificity: A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.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.Membrane Glycoproteins: Glycoproteins found on the membrane or surface of cells.Hydrogen-Ion Concentration: The normality of a solution with respect to HYDROGEN ions; H+. It is related to acidity measurements in most cases by pH = log 1/2[1/(H+)], where (H+) is the hydrogen ion concentration in gram equivalents per liter of solution. (McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed)Subcellular Fractions: 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)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.Cell Fractionation: Techniques to partition various components of the cell into SUBCELLULAR FRACTIONS.Prostaglandin Endoperoxides: Precursors in the biosynthesis of prostaglandins and thromboxanes from arachidonic acid. They are physiologically active compounds, having effect on vascular and airway smooth muscles, platelet aggregation, etc.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.Models, Biological: Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.Lipid Bilayers: Layers of lipid molecules which are two molecules thick. Bilayer systems are frequently studied as models of biological membranes.Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes.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.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Phosphoric Diester Hydrolases: A class of enzymes that catalyze the hydrolysis of one of the two ester bonds in a phosphodiester compound. EC 3.1.4.Microscopy, Electron: Microscopy using an electron beam, instead of light, to visualize the sample, thereby allowing much greater magnification. The interactions of ELECTRONS with specimens are used to provide information about the fine structure of that specimen. In TRANSMISSION ELECTRON MICROSCOPY the reactions of the electrons that are transmitted through the specimen are imaged. In SCANNING ELECTRON MICROSCOPY an electron beam falls at a non-normal angle on the specimen and the image is derived from the reactions occurring above the plane of the specimen.Detergents: Purifying or cleansing agents, usually salts of long-chain aliphatic bases or acids, that exert cleansing (oil-dissolving) and antimicrobial effects through a surface action that depends on possessing both hydrophilic and hydrophobic properties.Escherichia coli: A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc.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.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)Transfection: 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.Liposomes: Artificial, single or multilaminar vesicles (made from lecithins or other lipids) that are used for the delivery of a variety of biological molecules or molecular complexes to cells, for example, drug delivery and gene transfer. They are also used to study membranes and membrane proteins.Cyclooxygenase 1: A constitutively-expressed subtype of prostaglandin-endoperoxide synthase. It plays an important role in many cellular processes.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.Basement Membrane: A darkly stained mat-like EXTRACELLULAR MATRIX (ECM) that separates cell layers, such as EPITHELIUM from ENDOTHELIUM or a layer of CONNECTIVE TISSUE. The ECM layer that supports an overlying EPITHELIUM or ENDOTHELIUM is called basal lamina. Basement membrane (BM) can be formed by the fusion of either two adjacent basal laminae or a basal lamina with an adjacent reticular lamina of connective tissue. BM, composed mainly of TYPE IV COLLAGEN; glycoprotein LAMININ; and PROTEOGLYCAN, provides barriers as well as channels between interacting cell layers.Recombinant Fusion Proteins: Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.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.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.Models, Molecular: Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.Inositol 1,4,5-Trisphosphate: Intracellular messenger formed by the action of phospholipase C on phosphatidylinositol 4,5-bisphosphate, which is one of the phospholipids that make up the cell membrane. Inositol 1,4,5-trisphosphate is released into the cytoplasm where it releases calcium ions from internal stores within the cell's endoplasmic reticulum. These calcium ions stimulate the activity of B kinase or calmodulin.Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.Pyrones: Keto-pyrans.Cricetinae: A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.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).Guanosine 5'-O-(3-Thiotriphosphate): Guanosine 5'-(trihydrogen diphosphate), monoanhydride with phosphorothioic acid. A stable GTP analog which enjoys a variety of physiological actions such as stimulation of guanine nucleotide-binding proteins, phosphoinositide hydrolysis, cyclic AMP accumulation, and activation of specific proto-oncogenes.Adenosine Triphosphate: An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter.Bacterial Proteins: Proteins found in any species of bacterium.Calcimycin: An ionophorous, polyether antibiotic from Streptomyces chartreusensis. It binds and transports CALCIUM and other divalent cations across membranes and uncouples oxidative phosphorylation while inhibiting ATPase of rat liver mitochondria. The substance is used mostly as a biochemical tool to study the role of divalent cations in various biological systems.Receptors, Cell Surface: Cell surface proteins that bind signalling molecules external to the cell with high affinity and convert this extracellular event into one or more intracellular signals that alter the behavior of the target cell (From Alberts, Molecular Biology of the Cell, 2nd ed, pp693-5). Cell surface receptors, unlike enzymes, do not chemically alter their ligands.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).Tetradecanoylphorbol Acetate: A phorbol ester found in CROTON OIL with very effective tumor promoting activity. It stimulates the synthesis of both DNA and RNA.Phosphatidylethanolamines: Derivatives of phosphatidic acids in which the phosphoric acid is bound in ester linkage to an ethanolamine moiety. Complete hydrolysis yields 1 mole of glycerol, phosphoric acid and ethanolamine and 2 moles of fatty acids.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.1-Alkyl-2-acetylglycerophosphocholine Esterase: A lipoprotein-associated PHOSPHOLIPASE A2 which modulates the action of PLATELET ACTIVATING FACTOR by hydrolyzing the SN-2 ester bond to yield the biologically inactive lyso-platelet-activating factor. It has specificity for phospholipid substrates with short-chain residues at the SN-2 position, but inactive against long-chain phospholipids. Deficiency in this enzyme is associated with many diseases including ASTHMA, and HYPERCHOLESTEROLEMIA.Protein Transport: The process of moving proteins from one cellular compartment (including extracellular) to another by various sorting and transport mechanisms such as gated transport, protein translocation, and vesicular transport.Cyclic AMP: An adenine nucleotide containing one phosphate group which is esterified to both the 3'- and 5'-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and ACTH.Group X Phospholipases A2: A secreted phospholipase A2 subtype that contains a interfacial-binding region with specificity for PHOSPHATIDYLCHOLINE. This enzyme group may play a role in eliciting ARACHIDONIC ACID release from intact cellular membranes and from LOW DENSITY LIPOPROTEINS. Members of this group bind specifically to PHOSPHOLIPASE A2 RECEPTORS.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.Endoplasmic Reticulum: A system of cisternae in the CYTOPLASM of many cells. In places the endoplasmic reticulum is continuous with the plasma membrane (CELL MEMBRANE) or outer membrane of the nuclear envelope. If the outer surfaces of the endoplasmic reticulum membranes are coated with ribosomes, the endoplasmic reticulum is said to be rough-surfaced (ENDOPLASMIC RETICULUM, ROUGH); otherwise it is said to be smooth-surfaced (ENDOPLASMIC RETICULUM, SMOOTH). (King & Stansfield, A Dictionary of Genetics, 4th ed)Prostaglandins B: Physiologically active prostaglandins found in many tissues and organs. They are potent pressor substances and have many other physiological activities.Group V Phospholipases A2: A subcategory of secreted phospholipases A2 that contains both a negatively charged carboxy-terminal segment and interfacial-binding region specific for PHOSPHATIDYL CHOLINE-containing membranes. This enzyme group may play a role in the release of ARACHIDONIC ACID from phospholipid membranes.Prostaglandin Endoperoxides, Synthetic: Synthetic compounds that are analogs of the naturally occurring prostaglandin endoperoxides and that mimic their pharmacologic and physiologic activities. They are usually more stable than the naturally occurring compounds.Prostaglandins F, Synthetic: Analogs or derivatives of prostaglandins F that do not occur naturally in the body. They do not include the product of the chemical synthesis of hormonal PGF.Bee Venoms: Venoms obtained from Apis mellifera (honey bee) and related species. They contain various enzymes, polypeptide toxins, and other substances, some of which are allergenic or immunogenic or both. These venoms were formerly used in rheumatism to stimulate the pituitary-adrenal system.Golgi Apparatus: A stack of flattened vesicles that functions in posttranslational processing and sorting of proteins, receiving them from the rough ENDOPLASMIC RETICULUM and directing them to secretory vesicles, LYSOSOMES, or the CELL MEMBRANE. The movement of proteins takes place by transfer vesicles that bud off from the rough endoplasmic reticulum or Golgi apparatus and fuse with the Golgi, lysosomes or cell membrane. (From Glick, Glossary of Biochemistry and Molecular Biology, 1990)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)Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing HEMOGLOBIN whose function is to transport OXYGEN.Crotalid Venoms: Venoms from snakes of the subfamily Crotalinae or pit vipers, found mostly in the Americas. They include the rattlesnake, cottonmouth, fer-de-lance, bushmaster, and American copperhead. Their venoms contain nontoxic proteins, cardio-, hemo-, cyto-, and neurotoxins, and many enzymes, especially phospholipases A. Many of the toxins have been characterized.Snake Venoms: Solutions or mixtures of toxic and nontoxic substances elaborated by snake (Ophidia) salivary glands for the purpose of killing prey or disabling predators and delivered by grooved or hollow fangs. They usually contain enzymes, toxins, and other factors.Peptides: Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are linear polypeptides that are normally synthesized on RIBOSOMES.Cytoplasm: The part of a cell that contains the CYTOSOL and small structures excluding the CELL NUCLEUS; MITOCHONDRIA; and large VACUOLES. (Glick, Glossary of Biochemistry and Molecular Biology, 1990)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.Temperature: The property of objects that determines the direction of heat flow when they are placed in direct thermal contact. The temperature is the energy of microscopic motions (vibrational and translational) of the particles of atoms.Structure-Activity Relationship: 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.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.Lysophospholipids: Derivatives of PHOSPHATIDIC ACIDS that lack one of its fatty acyl chains due to its hydrolytic removal.Microscopy, Confocal: A light microscopic technique in which only a small spot is illuminated and observed at a time. An image is constructed through point-by-point scanning of the field in this manner. Light sources may be conventional or laser, and fluorescence or transmitted observations are possible.Membrane Transport Proteins: Membrane proteins whose primary function is to facilitate the transport of molecules across a biological membrane. Included in this broad category are proteins involved in active transport (BIOLOGICAL TRANSPORT, ACTIVE), facilitated transport and ION CHANNELS.Phospholipases A2, Calcium-Independent: A subcategory of structurally-related phospholipases A2 that do not require calcium for activity.Pertussis Toxin: One of the virulence factors produced by BORDETELLA PERTUSSIS. It is a multimeric protein composed of five subunits S1 - S5. S1 contains mono ADPribose transferase activity.Butanols: Isomeric forms and derivatives of butanol (C4H9OH).Microvilli: Minute projections of cell membranes which greatly increase the surface area of the cell.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).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.Virulence Factors, Bordetella: A set of BACTERIAL ADHESINS and TOXINS, BIOLOGICAL produced by BORDETELLA organisms that determine the pathogenesis of BORDETELLA INFECTIONS, such as WHOOPING COUGH. They include filamentous hemagglutinin; FIMBRIAE PROTEINS; pertactin; PERTUSSIS TOXIN; ADENYLATE CYCLASE TOXIN; dermonecrotic toxin; tracheal cytotoxin; Bordetella LIPOPOLYSACCHARIDES; and tracheal colonization factor.Cobra Venoms: Venoms from snakes of the genus Naja (family Elapidae). They contain many specific proteins that have cytotoxic, hemolytic, neurotoxic, and other properties. Like other elapid venoms, they are rich in enzymes. They include cobramines and cobralysins.Rats, Inbred Strains: Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding.Glycosylphosphatidylinositols: Compounds containing carbohydrate or glycosyl groups linked to phosphatidylinositols. They anchor GPI-LINKED PROTEINS or polysaccharides to cell membranes.6-Ketoprostaglandin F1 alpha: The physiologically active and stable hydrolysis product of EPOPROSTENOL. Found in nearly all mammalian tissue.Liver: A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.Protein Conformation: The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain).ThionesChromatography, Thin Layer: Chromatography on thin layers of adsorbents rather than in columns. The adsorbent can be alumina, silica gel, silicates, charcoals, or cellulose. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)Group IB Phospholipases A2: A subclass of group I phospholipases A2 that includes enzymes isolated from PANCREATIC JUICE. Members of this group have specificity for PHOSPHOLIPASE A2 RECEPTORS.Peptide Fragments: Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.Hydroxyprostaglandin Dehydrogenases: Catalyzes reversibly the oxidation of hydroxyl groups of prostaglandins.Fluorescent Antibody Technique: Test for tissue antigen using either a direct method, by conjugation of antibody with fluorescent dye (FLUORESCENT ANTIBODY TECHNIQUE, DIRECT) or an indirect method, by formation of antigen-antibody complex which is then labeled with fluorescein-conjugated anti-immunoglobulin antibody (FLUORESCENT ANTIBODY TECHNIQUE, INDIRECT). The tissue is then examined by fluorescence microscopy.Mutagenesis, Site-Directed: Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.Swine: 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).Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.Synaptic Membranes: Cell membranes associated with synapses. Both presynaptic and postsynaptic membranes are included along with their integral or tightly associated specializations for the release or reception of transmitters.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.Microscopy, Fluorescence: Microscopy of specimens stained with fluorescent dye (usually fluorescein isothiocyanate) or of naturally fluorescent materials, which emit light when exposed to ultraviolet or blue light. Immunofluorescence microscopy utilizes antibodies that are labeled with fluorescent dye.Phosphodiesterase Inhibitors: Compounds which inhibit or antagonize the biosynthesis or actions of phosphodiesterases.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.Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.Phosphatidylinositol Phosphates: Phosphatidylinositols in which one or more alcohol group of the inositol has been substituted with a phosphate group.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.Calcium Signaling: Signal transduction mechanisms whereby calcium mobilization (from outside the cell or from intracellular storage pools) to the cytoplasm is triggered by external stimuli. Calcium signals are often seen to propagate as waves, oscillations, spikes, sparks, or puffs. The calcium acts as an intracellular messenger by activating calcium-responsive proteins.Snakes: Limbless REPTILES of the suborder Serpentes.Biological Transport: The movement of materials (including biochemical substances and drugs) through a biological system at the cellular level. The transport can be across cell membranes and epithelial layers. It also can occur within intracellular compartments and extracellular compartments.Protein Processing, Post-Translational: Any of various enzymatically catalyzed post-translational modifications of PEPTIDES or PROTEINS in the cell of origin. These modifications include carboxylation; HYDROXYLATION; ACETYLATION; PHOSPHORYLATION; METHYLATION; GLYCOSYLATION; ubiquitination; oxidation; proteolysis; and crosslinking and result in changes in molecular weight and electrophoretic motility.Kidney: Body organ that filters blood for the secretion of URINE and that regulates ion concentrations.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).)Naphthalenes: Two-ring crystalline hydrocarbons isolated from coal tar. They are used as intermediates in chemical synthesis, as insect repellents, fungicides, lubricants, preservatives, and, formerly, as topical antiseptics.CHO Cells: CELL LINE derived from the ovary of the Chinese hamster, Cricetulus griseus (CRICETULUS). The species is a favorite for cytogenetic studies because of its small chromosome number. The cell line has provided model systems for the study of genetic alterations in cultured mammalian cells.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).Guinea Pigs: A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research.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.Platelet Activating Factor: A phospholipid derivative formed by PLATELETS; BASOPHILS; NEUTROPHILS; MONOCYTES; and MACROPHAGES. It is a potent platelet aggregating agent and inducer of systemic anaphylactic symptoms, including HYPOTENSION; THROMBOCYTOPENIA; NEUTROPENIA; and BRONCHOCONSTRICTION.ADP-Ribosylation Factors: MONOMERIC GTP-BINDING PROTEINS that were initially recognized as allosteric activators of the MONO(ADP-RIBOSE) TRANSFERASE of the CHOLERA TOXIN catalytic subunit. They are involved in vesicle trafficking and activation of PHOSPHOLIPASE D. This enzyme was formerly listed as EC 3.6.1.47

*Peripheral membrane protein

"The membrane binding domains of prostaglandin endoperoxide H synthases 1 and 2. Peptide mapping and mutational analysis". J ... Peripheral enzymes participate in metabolism of different membrane components, such as lipids (phospholipases and cholesterol ... Peripheral membrane proteins are membrane proteins that adhere only temporarily to the biological membrane with which they are ... Other phosphoinositide-binding proteins include phosphotyrosine-binding domain [25] and certain PDZ domains. They bind PtdIns(4 ...

*PTGS1

... released from membrane phospholipids at the sn-2 ester binding site by the enzymatic activity of phospholipase A2, to ... Cyclooxygenase 1 (COX-1), also known as prostaglandin G/H synthase 1, prostaglandin-endoperoxide synthase 1 or prostaglandin H2 ... Picot D, Loll PJ, Garavito RM (January 1994). "The X-ray crystal structure of the membrane protein prostaglandin H2 synthase-1 ... Prostaglandin-endoperoxide synthase (PTGS), also known as cyclooxygenase (COX), is the key enzyme in prostaglandin biosynthesis ...

*Orientations of Proteins in Membranes database

"The membrane binding domains of prostaglandin endoperoxide H synthases 1 and 2. Peptide mapping and mutational analysis". J ... "Changes in Ca2+ affinity upon activation of Agkistrodon piscivorus piscivorus phospholipase A2". Biochemistry. 40 (11): 3264- ... membrane topology, quaternary structure of proteins in membrane-bound state, and the type of a destination membrane for each ... Orientations of Proteins in Membranes (OPM) database provides spatial positions of membrane protein structures with respect to ...

*Methylprednisolone

Unbound glucocorticoids cross cell membranes and bind with high affinity to specific cytoplasmic receptors, modifying ... The anti-inflammatory actions of corticosteroids are thought to involve phospholipase A2 inhibitory proteins, lipocortins, ... which control the biosynthesis of potent mediators of inflammation such as prostaglandins and leukotrienes. Guanacastepene A ...

*Glycerophospholipid

... and membrane-bound enzymes. Marked alterations in neural membrane glycerophospholipid composition have been reported to occur ... such as prostaglandins, eicosanoids, platelet activating factor and diacylglycerol. Thus, neural membrane phospholipids are a ... Receptor-mediated degradation of glycerophospholipids by phospholipases A(l), A(2), C, and D results in generation of second ... Their amphipathic nature drives the formation of the lipid bilayer structure of membranes. The cell membrane seen under the ...

*15-Hydroxyeicosatetraenoic acid

The 15(S)-HpETE is bound primarily at the sn-2 position of these phospholipids (see Phospholipase) and may be reduced to 15(S)- ... 104:5-62, 1981 Marshall, Paul J.; Kulmacz, Richard J. (1988). "Prostaglandin H synthase: Distinct binding sites for ... 15(S)-HETE-containing-phospholipids may also be made directly by the action of 15-LO-1 on membrane phosphatidylinositols or ... The phosphatidylethanolamine-bound 15-HETE may be converted to phosphatidylethanolamine-bound 15-oxo-ETE. Oxygenated by 5- ...

*Prostaglandin DP2 receptor

G protein-coupled receptors (GPCRs) such as DP2 are integral membrane proteins that, when bound by their cognate ligands (or, ... which simulate phospholipase C to cleave phosphatidylinositol triphosphate into inositol triphosphate (IP3) and diacylglycerol ... It is a member of the class of prostaglandin receptors which bind with and respond to various prostaglandins. DP2 along with ... The following standard prostaglandins have the following relative affinities and potencies in binding to and activating DP2: ...

*Mometasone furoate

It is believed that the action of corticosteroid anti-inflammatory agents are bound to inhibitive proteins of phospholipase A2 ... Mometasone and other corticosteroids circulate in the blood easily, crossing cellular membranes and binding with cytoplasmic ... The lipocortins, in turn, control the biosynthesis of potent mediators of inflammation as the prostaglandins and leukotrienes, ... the reduction of the permeability of the capillary membranes and consequently edema, the reduction of complementary components ...

*CD36

In the absence of ligand, membrane bound CD36 exists primarily in a monomeric state. However exposure to the thrombospondin ... Recently, CD36 was linked to store-operated calcium flux, phospholipase A2 activation, and production of prostaglandin E2 CD36 ... Daviet L, Malvoisin E, Wild TF, McGregor JL (August 1997). "Thrombospondin induces dimerization of membrane-bound, but not ... phospholipase A2 activation, and production of prostaglandin E2". The Journal of Biological Chemistry. 286 (20): 17785-95. doi: ...

*Prostaglandin F2alpha

PGF2α acts by binding to the prostaglandin F2α receptor. It is released in response to an increase in oxytocin levels in the ... Action of PGF2α is dependent on the number of receptors on the corpus luteum membrane. The PGF2α isoform 8-iso-PGF2α was found ... First, Phospholipase A2 (PLA2) facilitates the conversion of phospholipids to Arachidonic Acid, the framework from which all ... 1978). "Prostaglandins and thromboxanes". Annual Review of Biochemistry. 47: 997-1029. CS1 maint: Explicit use of et al. (link ...

*Annexin A1

... prostaglandins and leukotrienes. They inhibit prostaglandin synthesis at the level of phospholipase A2 as well as at the level ... Augmentation by membrane phospholipids". J. Biol. Chem. 266 (2): 1101-8. PMID 1670773. Kovacic RT, Tizard R, Cate RL, et al. ( ... ANXA1 inhibits the activation of NF-κB by binding to the p65 subunit. The gene for annexin A1 (ANXA1) is upregulated in hairy ... Since phospholipase A2 is required for the biosynthesis of the potent mediators of inflammation, prostaglandins, and ...

*Diglyceride

... by the enzyme phospholipase C (PLC) (a membrane-bound enzyme) that, through the same reaction, produces inositol trisphosphate ... In addition to activating PKC, diacylglycerol has a number of other functions in the cell: a source for prostaglandins a ... The production of DAG in the membrane facilitates translocation of PKC from the cytosol to the plasma membrane. Munc13 ... Binding of DAG to the C1 domain of Munc13 increases the fusion competence of synaptic vesicles resulting in potentiated release ...

*Eicosanoid

These fatty acids are bound in ester linkage to the SN2 position of membrane phospholipids; PLA2s act as esterases to release ... doi:10.1016/j.prostaglandins.2011.09.001. PMID 21945326. Matsuoka T, Narumiya S (2007). "Prostaglandin receptor signaling in ... The activated cells then mobilize enzymes, termed phospholipase A2's (PLA2s), capable of releasing ω-6 and ω-3 fatty acids from ... They derive from the fatty acids that make up the cell membrane and nuclear membrane. These fatty acids must be released from ...

*Biochemical cascade

IP3 is released as a soluble structure into the cytosol and DAG remains bound to the membrane. IP3 binds to IP3 receptors, ... PLCγ (Phosphoinositide Phospholipase C γ) hydrolyzes membrane phospholipids to form IP3 (Inositoltriphosphate) and DAG ( ... The LH surge also leads to the production of progesterone and prostaglandins that induce the expression of ADAMTS1 and other ... are insoluble in water and membrane-associated, being localized at intermembrane spaces, where they can bind to membrane- ...

*Immune system

In humans, this response is activated by complement binding to antibodies that have attached to these microbes or the binding ... In HIV, the envelope that covers the virion is formed from the outermost membrane of the host cell; such "self-cloaked" viruses ... Eicosanoids include prostaglandins that produce fever and the dilation of blood vessels associated with inflammation, and ... Moreau JM, Girgis DO, Hume EB, Dajcs JJ, Austin MS, O'Callaghan RJ (Sep 2001). "Phospholipase A(2) in rabbit tears: a host ...

*Luteinizing hormone/choriogonadotropin receptor

Upon binding of LH to the external part of the membrane spanning receptor, a transduction of the signal takes place that ... The process is modified by prostaglandins. Other cellular regulators that participate are the intracellular calcium ... concentration modified by phospholipase, nitric acid, and other growth factors. In a feedback mechanism, these activated ... This can be accomplished by metabolizing bound LHCGR sites. The bound LCGR complex is brought by lateral migration to a coated ...

*Follicle-stimulating hormone receptor

The hormone-binding subdomain is responsible for the high-affinity hormone binding, and the signal-specificity subdomain, ... Upregulation refers to the increase in the number of receptor sites on the membrane. Estrogen upregulates FSH receptor sites. ... The process is modified by prostaglandins. Other cellular regulators are participate are the intracellular calcium ... concentration modified by phospholipase, nitric acid, and other growth factors. The FSH receptor can also activate the ...

*Fatty acid metabolism

... by the cell membrane bound enzyme phospholipase C (PLC). An example of a diacyl-glycerol shown on the right. This DAG is 1- ... The prostaglandins made from arachidonic acid stored in the cell membrane, are probably the most well known group of these ... The prostaglandins are synthesized in the cell membrane by the cleavage of arachidonate from the phospholipids that make up the ... This is catalyzed either by phospholipase A2 acting directly on a membrane phospholipid, or by a lipase acting on DAG (diacyl- ...

*Epoxyeicosatrienoic acid

Membrane-bound Microsomal epoxide hydrolase (mEH or Epoxide hydrolase 1 [EC 3.2.2.9.]) can metabolize EETs to their dihydroxy ... Prostaglandins & Other Lipid Mediators. 98 (3-4): 75-85. doi:10.1016/j.prostaglandins.2011.11.007. PMID 22173545. Bellien J, ... causes arachidonic acid to be released from the sn-2 position of cellular phospholipids through the action of Phospholipase A2- ... Prostaglandins & Other Lipid Mediators. 122: 45-53. doi:10.1016/j.prostaglandins.2015.12.007. PMID 26747234. Siler DA, Berlow ...

*Systemin

... the receptor that brassinolides bind to on the cell membrane. This was the first receptor which was found to be able to bind ... Lipids in the membrane are converted to arachidonic acid and then to prostaglandins, which are analogs of jasmonic acid. Both ... and linolenic acid is released from cell membranes after a phospholipase has been activated. Linolenic acid is then converted ... In 1994, tomato systemin was found to bind to a 50KDa protein in the cell membrane of tomato. The protein has a structure ...

*Prostaglandin

DP1-2 receptors bind to PGD2). The diversity of receptors means that prostaglandins act on an array of cells and have a wide ... inhibit phospholipase A2 production) COX-2 selective inhibitors or coxibs Cyclopentenone prostaglandins may play a role in ... demonstrated that diffusion alone cannot explain the penetration of prostaglandin through the cellular membrane. The release of ... Prostaglandin E2 (PGE2) is generated from the action of prostaglandin E synthases on prostaglandin H2 (prostaglandin H2, PGH2 ...

*Free fatty acid receptor 1

This membrane protein binds free fatty acids, acting as a nutrient sensor for regulating energy homeostasis. The protein FFA1 ... Prostaglandins Other Lipid Mediat. 89 (3-4): 82-8. doi:10.1016/j.prostaglandins.2009.05.003. PMID 19460454. Sum CS, Tikhonova ... This activation causes one of its subunits to dissociate from the receptor, which then activates phospholipase C (PLC) which is ... "Expression of the gene for a membrane-bound fatty acid receptor in the pancreas and islet cell tumours in humans: evidence for ...

*Lipid signaling

DAG remains bound to the membrane by its fatty acid "tails" where it recruits and activates both conventional and novel members ... Prostaglandins are formed through oxidation of arachidonic acid by cyclooxygenases and other prostaglandin synthases. There are ... C1P activate phospholipase A2 and is found, along with CK, to be a mediator of arachidonic acid released in cells in response ... ceramide readily flip-flops across membranes as supported by studies in membrane models and membranes from red blood cells ( ...

*PNPLA8

Tanaka H, Takeya R, Sumimoto H (Jul 2000). "A novel intracellular membrane-bound calcium-independent phospholipase A(2)". ... "Group VIB Ca2+-independent phospholipase A2gamma promotes cellular membrane hydrolysis and prostaglandin production in a manner ... and expression of a novel human intracellular membrane-associated calcium-independent phospholipase A(2)". J Biol Chem. 275 (14 ... Calcium-independent phospholipase A2-gamma is an enzyme that in humans is encoded by the PNPLA8 gene. GRCh38: Ensembl release ...

*Nicolas Bazan

Role of phospholipase A2 and membrane-derived lipid second messengers in excitable membrane function and transcriptional ... Prostaglandins 27:203-216, 1984 Birkle DL, Bazan NG: Effects of K+ depolarization on the synthesis of prostaglandins and ... Distinct platelet-activating factor binding sites in synaptic endings and in intracellular membranes of rat cerebral cortex. J ... from membranes during seizures and ischemia through phospholipase A2. This finding has been referred to as the "Bazan Effect". ...
TY - JOUR. T1 - Characterization of a rat brain phospholipase D isozyme. AU - Min, Do Sik. AU - Park, Seung Kiel. AU - Exton, John H.. PY - 1998/3/20. Y1 - 1998/3/20. N2 - We have recently cloned a cDNA encoding a phospholipase D (PLD) from rat brain and named it rPLD1. It shows 90% amino acid identity with the human PLD isoform hPLD1b. We have expressed rPLD1 as a histidine-tagged fusion protein in insect (Sf9) cells using the expression vector pBlueBacHis and purified the recombinant protein to homogeneity by Ni2+-agarose affinity chromatography. Phosphatidylinositol 4,5-P2 and phosphatidylinositol 3,4,5- P3 activated the PLD equipotently, but other acidic phospholipids were ineffective. The activity of rPLD1 was dependent on both Mg2+ and Ca2+. It was specific for phosphatidylcholine and showed a broad dependence on pH with optimum activity at pH 6.5-7.5. The enzyme was inhibited by oleate and activated by the small G proteins ARF3 and ...
article{1b8edece-ac08-4e30-9e8c-455b71ce3ca9, abstract = {The cholinergic regulation of phospholipase D activity was studied in SH-SY5Y human neuroblastoma cells with phosphatidylethanol formation as a specific marker for the enzyme activity. The muscarinic antagonists, hexahydrosiladifenidol and pirenzepine, inhibited carbachol-induced phosphatidylethanol formation in a concentration-dependent manner and the inhibitory constants indicated that muscarinic M1 receptors are responsible for the major part of the phospholipase D activation. The mechanism of receptor-mediated phospholipase D activation varies between different cell types and receptors. In SH-SY5Y cells, the carbachol-induced phospholipase D activity was inhibited by protein kinase C inhibitors. Since both phospholipases D and C are activated by muscarinic stimulation in SH-SY5Y ...
Studies carried out in many laboratories have demonstrated the activation of phospholipase D (PLD) by a variety of receptor agonists and in many cell types. The signal-dependent formation of phosphatidic acid (PA), by PLD-catalyzed hydrolysis of phosphatidylcholine (PC), may represent a novel and ubiquitous signal transduction pathway in mammalian cells. The mode(s) of coupling between agonist receptors and PLD activation are not well understood. Studies utilizing NIH-3T3 fibroblasts indicated that PLD activation by different mitogens involves distinct mechanisms. Protein kinase C (PKC) seems to play a role both as a mediator and as a modulator of PLD activation. The role of PKC was further examined in Swiss/3T3-derived fibroblasts which stably overexpress PKC-alpha. In these cells, both basal and agonist-stimulated PLD activity are higher than in control cells. In vitro analysis of PLD activity in detergent-solubilized cell membranes, utilizing exogenous ...
Glycosylphosphatidylinositol phospholipase D (EC 3.1.4.50, GPI-PLD, glycoprotein phospholipase D, phosphatidylinositol phospholipase D, phosphatidylinositol-specific phospholipase D) is an enzyme with systematic name glycoprotein-phosphatidylinositol phosphatidohydrolase. This enzyme catalyses the following chemical reaction 6-(alpha-D-glucosaminyl)-1-phosphatidyl-1D-myo-inositol + H2O ⇌ {\displaystyle \rightleftharpoons } 6-(alpha-D-glucosaminyl)-1D-myo-inositol + 3-sn-phosphatidate This enzyme cleaves proteins from the lipid part of the glycosylphosphatidylinositol (GPI) anchors. Phospholipase Low, M.G.; Prasad, A.R.S. (1988). "A phospholipase D specific for the phosphatidylinositol anchor of cell-surface proteins is abundant in plasma". Proc. Natl. Acad. Sci. USA. 85 (4): 980-984. ...
TY - JOUR. T1 - Quercetin-induced downregulation of phospholipase D1 inhibits proliferation and invasion in U87 glioma cells. AU - Park, Mi Hee. AU - Min, Do Sik. PY - 2011/9/9. Y1 - 2011/9/9. N2 - Phospholipase D (PLD) has been recognized as a regulator of cell proliferation and tumorigenesis, but little is known about the molecules regulating PLD expression. Thus, the identification of small molecules inhibiting PLD expression would be an important advance in PLD-mediated physiology. Quercetin, a ubiquitous bioactive flavonoid, is known to inhibit proliferation and induce apoptosis in a variety of cancer cells. In the present study, we examined the effect of quercetin on the expression of PLD in U87 glioma cells. Quercetin significantly suppressed the expression of PLD1 at the transcriptional level. Moreover, quercetin abolished the protein expression of PLD1 in a time and dose-dependent manner, as well as inhibited PLD activity. Quercetin ...
Phospholipase D (PLD) hydrolyzes the phosphodiester bond of the predominant membrane phospholipid, phosphatidylcholine producing phosphatidic acid and free choline. This activity can participate in signal transduction pathways and impact on vesicle trafficking for secretion and endocytosis, as well as receptor signalling. Phospholipids can regulate PLD activity directly, through specific intermolecular interactions, or indirectly, through their effect on the localization or activity of PLDs protein effectors. This short review highlights these various phospholipid inputs into the regulation of PLD activity and also reviews potential roles for PLD-generated phosphatidic acid, particularly a mechanism by which the phospholipid may participate in the process of vesicular trafficking.
TY - JOUR. T1 - Activation of endothelial cell phospholipase D by sphingosine and sphingosine-1-phosphate.. AU - Natarajan, V.. AU - Jayaram, H. N.. AU - Scribner, W. M.. AU - Garcia, J. G.. PY - 1994/8. Y1 - 1994/8. N2 - We have investigated the activation of phospholipase D (PLD) by sphingosine and its derivatives in bovine pulmonary artery endothelial cells (BPAEC) prelabeled with [32P]orthophosphate or [32P]lyso phospholipids. Sphingosine, in a dose- and time-dependent manner, stimulated the hydrolysis of [32P]phosphatidylcholine (PC) resulting in the production of [32P]phosphatidic acid (PA), suggesting PLD activation. In the presence of ethanol (150 mM), the accumulation of [32P]phosphatidylethanol was also observed. The sphingosine-induced stimulation of PLD activity was not affected by treatment with the protein kinase C (PKC) inhibitor staurosporine or by down-regulation of PKC with TPA and was independent of extracellular Ca2+, ...
One hallmark of cancer is an increase of cellular phosphocholine (PC) and total choline-containing compounds (tCho), which are closely related to malignant transformation, invasion and metastasis. Enzymes in choline metabolism present attractive targets that can be exploited for treatment. Choline kinase (Chk) is a cytosolic enzyme that catalyzes the phosphorylation of choline (Cho) to phosphocholine (PC) by using ATP in the presence of magnesium. Over-expression of Chk-α has been observed in breast, prostate and lung cancers, making it an obvious choice for targeting. Down-regulation of Chk-α results in a significant reduction of cell proliferation and increased differentiation in highly invasive MDA-MB-231 human breast cancer cells after siRNA-Chk transfection. Another potential target is phosphatidylcholine-specific phospholipase D (PC-PLD). Two mammalian isoforms of PLD, PLD1 and PLD2 have currently been identified. PLD1 is activated by G proteins such as ARF, Rho and ...
Transient forebrain ischemia results in delayed neuronal death in the CA1 region of the hippocampus after injury, which is, at least in part, a consequence of excessive generation of reactive oxygen species. Previous in vitro studies using cell cultures or brain slices have demonstrated that phospholipase D (PLD) in the nervous system is involved in the signaling mechanism in response to a variety of agonists. Several recent studies have shown that reactive oxygen species stimulate phospholipase D (PLD) activity in several kinds of cells. Therefore, this raises the possibility that PLD activity is enhanced in the ischemic brain. Meanwhile, osteopontin (OPN) was initially identified as a sialoglycoprotein in bone, but has since been found in various tissues. Although not much is known about its function, OPN seems to play an important role in inflammation and tissue repair. Recently, it was reported that OPN was upregulated in the activated ...
Stimulation of human neutrophils by the receptor agonist N-formylmethionyl-leucyl-phenylalanine (fMLP) results in a respiratory burst, catalysed by an NADPH oxidase. Concomitantly, phospholipase D (PLD) is activated. To investigate the role of protein kinase C (PKC) in these neutrophil responses, we have compared the effects of staurosporine and a structural analogue of staurosporine (cgp41251), that reflects a higher selectivity towards PKC [Meyer, Regenass, Fabbro, Alteri, Rösel, Müller, Caravatti and Matter (1989) Int. J. Cancer 43, 851-856]. Both staurosporine and cgp41251 dose-dependently inhibited the production of superoxide induced by phorbol 12-myristate 13-acetate (PMA). Both compounds also caused inhibition of the fMLP-induced respiratory burst, but with a lower efficacy during the initiation phase of this response. This latter observation cannot be taken as evidence against PKC involvement in the activation of the respiratory burst, because pretreatment of ...
Overexpression on plasma membrane of human epidermal growth factor receptor 2 (HER2) is reported in 25% to 30% of breast cancers. Heterodimer formation with cognate members of the epidermal growth factor receptor (EGFR) family, such as HER3 and EGFR, activates abnormal cell-signalling cascades responsible for tumorigenesis and further transcriptional HER2 gene upregulation. Targeting the molecular mechanisms controlling HER2 overexpression and recycling may effectively deactivate this feedback-amplification loop. We recently showed that inactivation of phosphatidylcholine-specific phospholipase C (PC-PLC) may exert a pivotal role in selectively modulating the expression on the membrane of specific receptors or proteins relevant to cell function. In the present study, we investigated the capability of PC-PLC inhibition to target the molecular mechanisms controlling HER2 overexpression on the membrane of breast cancer cells by ...
P164 Angiotensin II (Ang II) promotes arachidonic acid (AA) release via activation of cytosolic phospholipase A2 (cPLA2) and D (PLD) in rabbit vascular smooth muscle cells (VSMC). Ang II also stimulates the Ras/MAP kinase pathway, and MAP kinase activates cPLA2 and PLD in VSMC. The increase in Ras/MAP kinase activity elicited by Ang II in VSMC is mediated by 20-hydroxyeicosatetraenoic acid (HETE) and to a lesser extent by 12(S)-HETE, metabolites of AA generated by cytochrome P450 (CYP) and lipoxygenase (LO), respectively, upon activation of cPLA2 by calcium calmodulin-dependent kinase II. The purpose of this study was to determine if Ang II-induced PLD activation stimulation in VSMC from rabbit aorta is mediated by the Ras/MAP kinase pathway via AA metabolites generated by cPLA2. Ang II (100 nM) increased PLD activity measured as the production of 3H-phosphatidylethanol from phospholipids in VSMC prelabeled with 3H-oleic. Inhibitors of PLD (C2-ceramide, 10 μM), phosphatidate ...
Acute exercise causes a temporary short lasting activation of blood coagulation, platelet function and the prostaglandin system, the extent of these alterations being significantly less pronounced in...
Wright, Michelle H., Farquhar, Michelle J., Aletrari, Mina-Olga , Ladds, Graham and Hodgkin, Matthew N.. (2008) Identification of caspase 3 motifs and critical aspartate residues in human Phospholipase D1b and Phopsholipase D2a. Biochemical and Biophysical Research Communications, Vol.369 (No.2). pp. 478-484. ISSN 0006-291x ...
Phosphatidylinositol-glycan-specific phospholipase D is an enzyme that in humans is encoded by the GPLD1 gene. Many proteins are tethered to the extracellular face of eukaryotic plasma membranes by a glycosylphosphatidylinositol (GPI) anchor. The GPI-anchor is a glycolipid found on many blood cells. The protein encoded by this gene is a GPI degrading enzyme. Glycosylphosphatidylinositol specific phospholipase D1 hydrolyzes the inositol phosphate linkage in proteins anchored by phosphatidylinositol glycans, thereby releasing the attached protein from the plasma membrane. GPLD1 has been shown to interact with Apolipoprotein A1 and APOA4. GRCh38: Ensembl release 89: ENSG00000112293 - Ensembl, May 2017 GRCm38: Ensembl release 89: ENSMUSG00000021340 - Ensembl, May 2017 "Human PubMed Reference:". "Mouse PubMed Reference:". Schofield JN, Rademacher TW (Dec 2000). "Structure and expression of the human ...
TY - JOUR. T1 - Cooperative function of PLDδ and PLDα1 in abscisic acid-induced stomatal closure in arabidopsis. AU - Uraji, Misugi. AU - Katagiri, Takeshi. AU - Okuma, Eiji. AU - Ye, Wenxiu. AU - Hossain, Mohammad Anowar. AU - Masuda, Choji. AU - Miura, Aya. AU - Nakamura, Yoshimasa. AU - Mori, Izumi. AU - Shinozaki, Kazuo. AU - Murata, Yoshiyuki. PY - 2012/5. Y1 - 2012/5. N2 - Phospholipase D (PLD) is involved in responses to abiotic stress and abscisic acid (ABA) signaling. To investigate the roles of two Arabidopsis (Arabidopsis thaliana) PLDs, PLDα1 and PLDδ, in ABA signaling in guard cells, we analyzed ABA responses in guard cells using Arabidopsis wild type, pldα1 and pldδ single mutants, and a pldα1 pldδ double mutant. ABA-induced stomatal closure was suppressed in the pldα1 pldδ double mutant but not in the pld single mutants. The pldα1 and pldδ mutations reduced ABAinduced phosphatidic acid production in epidermal tissues. Expression of either PLDα1 or PLDδ ...
The prostaglandins (PG) are a group of physiologically active lipid compounds having diverse hormone-like effects in animals. Prostaglandins have been found in almost every tissue in humans and other animals. They are derived enzymatically from fatty acids. Every prostaglandin contains 20 carbon atoms, including a 5-carbon ring. They are a subclass of eicosanoids and of the prostanoid class of fatty acid derivatives. The structural differences between prostaglandins account for their different biological activities. A given prostaglandin may have different and even opposite effects in different tissues in some cases. The ability of the same prostaglandin to stimulate a reaction in one tissue and inhibit the same reaction in another tissue is determined by the type of receptor to which the prostaglandin binds. They act as autocrine or paracrine factors with their target cells present in the immediate vicinity of the site of their secretion. ...
The phorbol ester tumor promoter (12-0-tetradecanoyl-phorbol-13-acetate (10-7-10-9 M) caused a rapid (1-3 hr after addition) release of arachidonic acid and prostaglandins E2 and F2α from chick embryo fibroblasts. This effect was inhibited by cycloheximide and puromycin. Prostaglandin release was more sensitive to inhibition than was arachidonic acid release. Indomethacin, a cyclooxygenase inhibitor, completely blocked TPA-induced prostaglandin synthesis and slightly enhanced arachidonic acid release. Despite the complete suppression of prostaglandin synthesis, indomethacin caused only a 20-30% inhibition of TPA induction of plasminogen activator. Phorbol 12,13-didecanoate, phorbol-l2,13-dibenzoate and mezerein were also potent inducers of arachidonic acid and prostaglandin release, while phorbol and 4α phorbol didecanoate were inactive. All trans retinoic acid (10-5-10-6 M) inhibited TPA-induced arachidonic acid and prostaglandin release; retinyl palmitate and β-carotene were less effective ...
We thank Tsikas et al1 for the interest in our findings. An underlying concern of Tsikas et al1 is our use of an immunoassay for the determination of prostaglandins,2 a method that most studies on prostaglandins in the literature have used. Their point is that our prostaglandin values in muscle microdialysate are too high. Our measured levels are very similar to those observed by others in interstitial fluid from skeletal muscle,3 as well as from peritendinous tissue.4 The prostaglandin concentrations in these studies have been measured by radioimmunoassay, different than the immunoassay used by our group, yet resulting in similar values. The observation that our concentrations are higher than those observed by others in plasma is not surprising; we often observe large differences in concentrations of compounds between plasma and interstitial fluid. It may be true that, for methodologic/technical reasons, urine is a better fluid to measure prostaglandins in; ...
Phospholipase D2兔多克隆抗体(ab78907)可与人样本反应并经WB, ELISA, IHC实验严格验证。所有产品均提供质保服务,中国75%以上现货。
We have demonstrated previously the potent activation of PLD by the chemokine IL-8 in T lymphocytes (18). We have now extended our findings to include the C-C chemokine RANTES in demonstrating that in the Jurkat T cell line, the activation of this enzyme occurs at subnanomolar concentrations and is dependent on the activation of small GTP-binding protein cofactors. RANTES-induced PLD activation is consistently maximal at 1 nM, a concentration corresponding to the optimal chemotaxis-inducing dose in normal T lymphocytes. Interestingly, PLD activation in T lymphocytes and Jurkat T cells appears to be an important biologic consequence of chemokine action and more readily measurable (at nanomolar concentrations) than readouts of receptor activation such as calcium flux. It was also apparent that RANTES is the only chemokine tested to date (RANTES, MIP-1α, MIP-1β, MCP-1, MCP-3, lymphotactin) that induces as robust a response as seen in this study, although the others listed were capable of low ...
TY - JOUR. T1 - Thrombin induces proliferation of osteoblast-like cells through phosphatidylcholine hydrolysis. AU - Suzuki, Atsushi. AU - Kozawa, Osamu. AU - Shinoda, Junji. AU - Watanabe, Yasuko. AU - Saito, Hidehiko. AU - Oiso, Yutaka. PY - 1996/7/1. Y1 - 1996/7/1. N2 - We examined the effect of thrombin on phosphatidylcholine-hydrolyzing phospholipase D activity in osteoblast-like MC3T3-E1 cells. Thrombin stimulated the formation of choline dose dependently in the range between 0.01 and 1 U/ml, but not the phosphocholine formation. Diisopropylfluorophosphate (DFP)-inactivated thrombin had little effect on the choline formation. The combined effects of thrombin and 12-O-tetradecanoylphorbol-13-acetate, a protein kinase C-activating phorbol ester, on the choline formation were additive. Staurosporine, an inhibitor of protein kinases, had little effect on the thrombin-induced formation of choline. Combined addition of thrombin and NaF, an activator of heterotrimeric ...
This study was undertaken to define pathways by which LPS might activate the ERK kinases in alveolar macrophages. We hypothesized that LPS activates a PC-PLC, leading to production of DAG, an activator of sphingomyelinase activity. This, in turn, results in increased amounts of ceramide, an important effector molecule, which activates PKC ζ. PKC ζ activates MEK, which subsequently leads to ERK kinase activation. To test this hypothesis, we showed that LPS activates the ERK 2 kinase in alveolar macrophages and that this activation is inhibited by D609, a relatively specific inhibitor of PC-PLC. We next showed that LPS increases amounts of DAG and ceramide and that both of these effects of LPS are inhibited by D609. Our present studies indicate that LPS induction of DAG in alveolar macrophages is derived, at least in part, from a PC-containing phospholipid. Thus, we conclude from these experiments that the LPS-induced DAG is derived from hydrolysis of PC via activation of PC-PLC. In separate ...
Balaji Krishnan, Ph.D., and colleagues have proposed two types of studies to explore the role of phospholipase D1 in synapse degeneration and Alzheimers disease. For the first type of study, the researchers will obtain samples of tissue from autopsy specimens and use biochemical methods to measure the activity of phospholipase D1. The team will study how the activity of this protein changes in people who have mild cognitive impairment, a condition that sometimes precedes Alzheimers, and those that go on to develop Alzheimers disease. For the second study, Dr. Krishnan and colleagues will use mice that have been genetically altered to have an Alzheimers-like condition. The researchers will treat the mice with a drug known to inhibit phospholipase D1, and then measure how such treatment affects the onset or progression of Alzheimers like changes in brain function and behavior. Impact ...
The action of purified phospholipases on monomolecular films of various interfacial pressures is compared with the action on erythrocyte membranes. The phospholipases which cannot hydrolyse phospholipids of the intact erythrocyte membrane, phospholipase C from Bacillus cereus, phospholipase A2 from pig pancreas and Crotalus adamanteus and phospholipase D from cabbage, can ... read more hydrolyse phospholipid monolayers at pressure below 31 dynes/cm only. The phospholipases which can hydrolyse phospholipids of the intact erythrocyte membrane, phospholipase C from Clostridium welchii phospholipase A2 from Naja naja and bee venom and sphingomyelinase from Staphylococcus aureus, can hydrolyse ...
Two widely expressed mammalian phosphatidylcholine (PC)-specific phospholipases D (PLD), PLD1 and PLD2, have been identified. Recombinantly expressed PLD2 has high basal activity and is insensitive to GTP-binding protein activators of PLD1 [Colley, W. C., et al. (1997) Curr. Biol. 7, 191-201]. To investigate the regulation of PLD2 we isolated PLD2, from mouse brain by immunoaffinity chromatography. The native and recombinant proteins have indistinguishable properties: PLD2 is potently activated by phosphoinositides with a vicinal 4,5-phosphate pair but is not stimulated by guanosine 5-O-(3-thio triphosphate)-activated ADP-ribosylation factor-1, Rho family GTP-binding proteins, or protein kinases C-alpha, or -beta1 ...
Calcium dependent phospholipase A2 activity in the mixed micelles of 1-palmitoyl-2-oleoyl-phosphatidylglycerol and cholate was measured in sera of 39 patients with Crohns disease, 40 patients with ulcerative colitis, and 40 healthy controls. The phospholipase A2 activity was significantly raised in those sera of the patients with active Crohns disease and those with moderate and severe ulcerative colitis. The major phospholipase A2 activity derived from the sera was separated into two peaks by reverse phase high performance liquid chromatography. The phospholipase A2 active fractions were immunochemically characterised using specific antibody directed against human group II phospholipase A2 purified from rheumatoid synovial fluid. The results suggest that raised serum phospholipase A2 activity in patients ...
Find out about the science and chemistry of Prostaglandin (Prostaglandin I2), see colourful images of Prostaglandin and explore interactive 3D molecules of Prostaglandin
Find out about the science and chemistry of Prostaglandin (Prostaglandin D2), see colourful images of Prostaglandin and explore interactive 3D molecules of Prostaglandin
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Definition of prostaglandin in the Financial Dictionary - by Free online English dictionary and encyclopedia. What is prostaglandin? Meaning of prostaglandin as a finance term. What does prostaglandin mean in finance?
Rabbit polyclonal antibody raised against synthetic phosphopeptide of human PLD2. Synthetic phosphopeptide (conjugated with KLH) corresponding to residues surrounding Y169 of human PLD2. (PAB29251) - Products - Abnova
AIMS: To examine the potential role of the lipolytic enzyme phospholipase A2, produced by Helicobacter pylori in ulcer formation. METHODS: Phospholipase A2 activity in H pylori was compared with that in 10 commonly occurring pathogenic bacteria. Phospholipase A2 activity and its cytotoxic metabolite, lysolecithin, in the basal gastric aspirates of 12 patients infected with H pylori were compared with those in 12 subjects not infected with H pylori. RESULTS: The phospholipase A2 activity in H pylori was substantially higher than that in most of the other bacteria tested, and the activities of phospholipase A2 and lysolecithin in the basal gastric aspirates of those infected with H pylori were significantly higher than the activities found in the basal gastric aspirates of subjects who were not infected. The lysolecithin proportion of total ...
Purpose: : Pterygium is an ocular surface disease of unknown etiology characterized by growth of fibrovascular tissue from conjunctiva onto the cornea. The phospholipase(PL)-D is a class of enzymes involved in inflammation and differentiation. In cultured corneal epithelial cells, PLD plays a role in wound healing, and in other contexts they suppress apoptosis and increases cell motility. We aimed to investigate the presence of PLD subtypes in native ocular surface tissue and pterygium. Methods: : This study involved paired control or un-involved conjunctival and pterygium tissues. Reverse transcription semi-quantitative and quantitative PCR were performed to assess transcript levels for PLD1-5 in normal conjunctiva and pterygium tissue. Immunofluorescent staining using antibodies against PLD1/2 was used to investigate expression and tissue distribution. Western blots were performed for protein detection and to confirm the specificity of the antibodies used. Results: : ...
Prostaglandin(PG) D,SUB,2,/SUB, and PGE,SUB,2,/SUB, are major cyclooxygenase metabolites of arachidonic acid produced during allergic reactions including asthma. However, the role of PGD,SUB,2,/SUB, and PGE,SUB,2,/SUB, in allergic inflammation has long been ambiguous. This is partly because non-steroidal anti-inflammatory drugs that inhibit prostanoid synthesis are generally ineffective in allergic disorders. Both PGs exert their actions by acting on G-proteincoupled receptors; PGD,SUB,2,/SUB, acts at the PGD receptor(DP), PGE,SUB,2,/SUB, acts at four subtypes of PGE receptor, EP1 to EP4. To dissect the roles of PGD,SUB,2,/SUB,-DP pathway and each PGE,SUB,2,/SUB,-EP pathway in allergic reactions, we subject mice deficient in DP, EP1, EP2, EP3 and EP4 receptor individually to ovalbumin-induced allergic asthma as a model of type I allergy. These studies have revealed that there are opposing actions between two prostanoid pathways in allergic reactions; PGD,SUB,2,/SUB,-DP pathway and ...
Phospholipids and lipid second messengers mediate mitogenic signal transduction and oncogenesis, but there have been few successful examples of small molecules that affect biologically important phospholipid metabolism. Here we investigated the actions of a previously described antitumor agent, 4-(benzyl-(2-[(2,5-diphenyloxazole-4-carbonyl)amino]ethyl)carbamoyl) -2-decanoylaminobutyric acid (SC-ααδ9), which has antisignaling properties, on phospholipases. Although SC-ααδ9 had been shown to be a potent and selective inhibitor of the Cdc25 family of dual-specificity phosphatases, many of its cellular effects are not readily reconciled with phosphatase inhibition. Molecular modeling studies suggested that SC-ααδ9 shared several structural features with membrane phospholipids. Enzyme inhibition studies in vitro revealed that SC-ααδ9 was a potent inhibitor of phospholipase C (PLC; IC50 = 25 μM) but did not inhibit ...
PubMed comprises more than 30 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
Bacteria colony counts in peripheral blood and in bronchoalveolar lavage fluid (BALF) were also markedly decreased in PLD2−/− mice versus WT (Fig. 3 a). Bacteria released into the peritoneal cavity eventually make their way through the circulation and enter lung tissue, resulting in lung inflammation (Matute-Bello et al., 2001). Bacteria colony counts in lung tissues were also significantly decreased in PLD2−/− mice versus WT (Fig. 3 a). Live bacterial colony numbers were significantly increased in liver and spleen 24 h after CLP in WT mice compared with PLD2−/− mice (Fig. 3 a).. It was recently reported that neutrophils generate NETs to trap and kill invading bacteria (Brinkmann et al., 2004). To investigate the effect of PLD2 deficiency on NET formation, we stained neutrophils with SYTOX Green nucleic acid stain, a nonpermeable dye that stains nucleic acid, a primary component of NETs. Stimulation of neutrophils isolated from WT mice with ionomycin induced NET formation (Fig. 3 d). ...
Looking for online definition of 180 kDa secretory phospholipase A2 receptor in the Medical Dictionary? 180 kDa secretory phospholipase A2 receptor explanation free. What is 180 kDa secretory phospholipase A2 receptor? Meaning of 180 kDa secretory phospholipase A2 receptor medical term. What does 180 kDa secretory phospholipase A2 receptor mean?
Phosphatidylethanol (PEth) is an alcohol biomarker with a high degree of specificity; blood concentration of PEth correlates to the amount of alcohol consumed. This application note describes the extraction of three common species of PEth from whole blood using ISOLUTE® SLE+ supported liquid extraction prior to HPLC-MS/MS analysis. This simple sample preparation procedure produces clean extracts, good recoveries with low RSD, and LOQ from 20 ng/mL, and can be fully automated using Biotage® Extrahera™. 96 samples can be processed in 22 minutes and 33 seconds.. ISOLUTE SLE+ supported liquid extraction fixed-well plates offer an efficient alternative to traditional liquid-liquid extraction (LLE) for bioanalytical sample preparation, providing high analyte recoveries, no emulsion formation, and significantly reduced sample preparation time.. ...
Phosphatidylethanol (PEth) is an alcohol biomarker with a high degree of specificity; blood concentration of PEth correlates to the amount of alcohol consumed. This application note describes the extraction of three common species of PEth from whole blood using ISOLUTE® SLE+ supported liquid extraction prior to HPLC-MS/MS analysis. This simple sample preparation procedure produces clean extracts, good recoveries with low RSD, and LOQ from 20 ng/mL, and can be fully automated using Biotage® Extrahera™. 96 samples can be processed in 22 minutes and 33 seconds.. ISOLUTE SLE+ supported liquid extraction fixed-well plates offer an efficient alternative to traditional liquid-liquid extraction (LLE) for bioanalytical sample preparation, providing high analyte recoveries, no emulsion formation, and significantly reduced sample preparation time.. ...
Marian Blanca Ramírez from the CSIC in Spain has been studying the effects of LRRK2, a protein associated with Parkinsons disease, on cell motility. A Travelling Fellowship from Journal of Cell Science allowed her to spend time in Prof Maddy Parsons lab at Kings College London, learning new cell migration assays and analysing fibroblasts cultured from individuals with Parkinsons. Read more on her story here. Where could your research take you? The deadline to apply for the current round of Travelling Fellowships is 23rd Feburary 2018. Apply now!. ...
PubMed comprises more than 30 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
We have previously shown that recombinant interleukin 1 (IL-1) and recombinant tumour necrosis factor (TNF) synergistically stimulate phospholipase A2 release from mesangial cells. We now report that treatment of mesangial cells with the ′-agonist salbutamol, prostaglandin E2 (PGE2), cholera toxin or forskolin, which all activate adenylate cyclase, increased release of phospholipase A2 activity. Likewise, addition of a membrane-permeant cyclic AMP (cAMP) analogue or the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine enhanced release of phospholipase A2 activity from mesangial cells. There was a lag period of about 8 h before a significantly enhanced secretion could be detected. Furthermore, actinomycin D or cycloheximide completely suppressed cAMP-stimulated secretion of phospholipase A2. Angiotensin II, the phorbol ester phorbol 12-myristate ...
Has phosphatidylinositol transfer activity. Involved in the regulation of the phospholipid composition of plasma- and endomembranes. Altering plasma membrane composition may provide a possible mechanism for multidrug resistance. Involved in the regulation of sterol biosynthesis. Contributes to efficient phospholipase D1 activation in the regulation of phospholipid turnover.
Spiders of the genus Loxosceles, popularly known as Brown spiders, are considered a serious public health issue, especially in regions of hot or temperate climates, such as parts of North and South America. Although the venoms of these arachnids are complex in molecular composition, often containing proteins with distinct biochemical characteristics, the literature has primarily described a family of toxins, the Phospholipases-D (PLDs), which are highly conserved in all Loxosceles species. PLDs trigger most of the major clinical symptoms of loxoscelism i.e., dermonecrosis, thrombocytopenia, hemolysis, and acute renal failure. The key role played by PLDs in the symptomatology of loxoscelism was first described 40 years ago, when researches purified a hemolytic toxin that cleaved sphingomyelin and generated choline, and was referred to as a Sphingomyelinase-D, which was subsequently changed to Phospholipase-D when it was demonstrated that the ...
TY - JOUR. T1 - Nuclear Diacylglycerol Kinase-θ is Activated in Response to α-Thrombin. AU - Bregoli, Lisa. AU - Baldassare, Joseph J.. AU - Raben, Daniel Max. PY - 2001/6/29. Y1 - 2001/6/29. N2 - Currently, there is substantial evidence that nuclear lipid metabolism plays a critical role in a number of signal transduction cascades. Previous work from our laboratory showed that stimulation of quiescent fibroblasts with α-thrombin leads to the production of two lipid second messengers in the nucleus: an increase in nuclear diacylglycerol mass and an activation of phospholipase D, which catalyzes the hydrolysis of phosphatidylcholine to generate phosphatidic acid. Diacylglycerol kinase (DGK) catalyzes the conversion of diacylglycerol to phosphatidic acid, making it an attractive candidate for a signal transduction component. There is substantial evidence that this activity is indeed regulated in a number of signaling cascades (reviewed by van Blitterswijk, W. J., and Houssa, ...
Free Online Library: Cerebrospinal fluid secretory [Ca.sup.2+]-dependent phospholipase [A.sub.2] activity is increased in alzheimer disease.(Proteomics and Protein Markers) by Clinical Chemistry;
Phospholipase D2 (PLD2) has been found localized in low-density caveolin-rich membrane microdomains. Our previous study suggested that PLD2 and aquaporin 3 (AQP3) interact in these domains to inhibit keratinocyte proliferation and promote differentiation by cooperating to produce phosphatidylglycerol. To examine the effect of membrane microdomain localization on the PLD2/AQP3 signaling module and keratinocyte proliferation and differentiation, we treated mouse keratinocytes with 3 µM cell-permeable caveolin-1 scaffolding domain peptide or a negative control peptide and stimulated cell differentiation using a moderately elevated extracellular calcium concentration (125 uM) to maximally promote differentiation and phosphatidylglycerol production. Cell proliferation, differentiation, total PLD activity, phosphatidylglycerol levels, and AQP3 activity were monitored. The caveolin-1 scaffolding domain peptide itself had no effect on ...
Phagocytic leukocytes play a key role in innate immune responses, and classic chemotactic peptide receptors such as FPR or FPRL1 are involved in the modulation of this phagocyte activity (Le et al., 2001b). Although the signaling mechanisms of FPR have been well studied, the signaling pathways of FPRL1 have not been investigated systematically. In the present study, we examined the events downstream of FPRL1 in human neutrophils and found that the activation of FPRL1 caused Ca2+ increase via PLC-β activation in a PTX-sensitive manner, resulting in PKC/PLD-mediated NADPH oxidase stimulation. FPRL1 stimulation also caused PI3K activity-dependent Akt (data not shown) or ERK activation that elicited cPLA2 activation. Nonreceptor tyrosine kinases, such as FAK, were also activated (data not shown), and this FAK activity induced paxillin phosphorylation.. Although the role of chemotactic peptide receptors is generally regarded to be important, and many different ligands for receptors have been ...
In the presented study, we demonstrate that the interaction of group IVA cytosolic phospholipase A2 and ceramide-1-phosphate is crucial for production of eicosanoid synthesis in inflammation. Inflammation is a critical component of many disease states including anaphylaxis, cancer, cardiovascular disease, rheumatoid arthritis, diabetes and asthma. Eicosanoids are well established mediators of inflammation, and the initial rate limiting step in the production of eicosanoids is the liberation of arachidonic acid (AA) from membrane phospholipids by a phospholipase A2 (PLA2). The major phospholipase involved in this liberation of AA during the inflammatory response is group IVA cytosolic phospholipase A2 (cPLA2α). Previous studies from our laboratory demonstrated that the bioactive sphingolipid, ceramide-1-phosphate (C1P), binds cPLA2α at a three amino acid ...
Esta Tabla de HKD/SCR le permite consultar el historial de tipos de cambio correspondiente a este par de divisas durante un máximo de 10 años. XE utiliza tipos de cambio del mercado medio en tiempo real, que son sumamente precisos y provienen de más de 150 fuentes de tipos de cambio.
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0004]The present invention comprises the method of treating host organisms (i.e. human or animal) in need of a drug having anti-neoplastic activity comprising the administration of a therapeutically effective amount of venom anti-serum either alone or preferably in combination with a Phospholipase C inhibitor of non-toxic nature or monoclonal or polyclonal anti-serum to Phospholipase C enzyme or a vaccine containing in whole or in part venom and/or other components of animal, insect or plant origin showing Phospholipase A2 and/or Phospholipase C activity. This patent presents pharmaceutical formulations containing snake and/or insect venoms, or extracts from such venoms which may contain, total or partial, Phospholipase A2 enzyme activity alone or in combination with animal or plant Phospholipase A2 with or ...
In this study, some PLDs who were in need of kidney transplant experienced delays in access to transplantation because of delays in (1) being added to the kidney waiting list, (2) being listed in active status, and (3) receiving PLD priority. Many PLDs are exposed to months or years on dialysis before being added to the waiting list, with only 40.7% of registrations occurring before initiation of maintenance dialysis, and one half of PLDs who do not receive preemptive transplants are on dialysis for 332 days or longer before listing. Given that waiting time and time on dialysis are not major determinants of organ offers for PLDs, this practice exposes PLDs to potentially avoidable time on dialysis. After listing, most PLDs are put in active status in a timely manner, but a substantial number (14.0%) remains ineligible to receive organ offers because of inactive status for ,1 year. There are valid medical and other reasons why a candidate could be kept in inactive status; it is impossible to ...
L-β,γ-DIPALMITOYL-α-PHOSPHATIDIC ACID DISODIUM SALT 71065-87-7 NMR spectrum, L-β,γ-DIPALMITOYL-α-PHOSPHATIDIC ACID DISODIUM SALT H-NMR spectral analysis, L-β,γ-DIPALMITOYL-α-PHOSPHATIDIC ACID DISODIUM SALT C-NMR spectral analysis ect.
PLD4 Fragment MS Protein Standard, is a protein fragment containing a 50-150 amino acid sequence identical to part of a human PLD4 protein target. The fragment MS Protein Standard represents a new category of using heavy isotope labeled (15N, 13C) Lysine and Arginine residues resulting in more than 99% isotope incorporation, as internal MS standards offering distinct advantages to existing products for relative and absolute quantification.
Endothelin-1 (ET-1) plays an important role in tissue remodelling and fibrogenesis by inducing synthesis of collagen I via protein kinase C (PKC). ET-1 signals are transduced by two receptor subtypes, the ETA- and ETB-receptors which activate different Gα proteins. Here, we investigated the expression of both ET-receptor subtypes in human primary dermal fibroblasts and demonstrated that the ETA-receptor is the major ET-receptor subtype expressed. To determine further signalling intermediates, we inhibited Gαi and three phospholipases. Pharmacologic inhibition of Gαi, phosphatidylcholine-phospholipase C (PC-PLC) and phospholipase D (PLD), but not of phospholipase Cβ, abolished the increase in collagen I by ET-1. Inhibition of all phospholipases revealed similar effects on TGF-β1 induced collagen I synthesis, demonstrating involvement of ...
article{2049007, abstract = {BACKGROUND: Male factor and idiopathic infertility contribute significantly to global infertility, with abnormal testicular gene expression considered to be a major cause. Certain types of male infertility are caused by failure of the sperm to activate the oocyte, a process normally regulated by calcium oscillations, thought to be induced by a sperm-specific phospholipase C, PLCzeta (PLC zeta). Previously, we identified a point mutation in an infertile male resulting in the substitution of histidine for proline at position 398 of the protein sequence (PLC zeta(H398P)), leading to abnormal PLC zeta function and infertility. METHODS AND RESULTS: Here, using a combination of direct-sequencing and mini-sequencing of the PLC zeta gene from the patient and his family, we report the identification of a second PLC zeta mutation in the same patient resulting in a histidine to leucine substitution at position 233 (PLC zeta(H233L)), which is predicted to ...
Phospholipase C gamma: A phosphoinositide phospholipase C subtype that is primarily regulated by PROTEIN-TYROSINE KINASES. It is structurally related to PHOSPHOLIPASE C DELTA with the addition of SRC HOMOLOGY DOMAINS and pleckstrin homology domains located between two halves of the CATALYTIC DOMAIN.
BACKGROUND: Male factor and idiopathic infertility contribute significantly to global infertility, with abnormal testicular gene expression considered to be a major cause. Certain types of male infertility are caused by failure of the sperm to activate the oocyte, a process normally regulated by calcium oscillations, thought to be induced by a sperm-specific phospholipase C, PLCzeta (PLCζ). Previously, we identified a point mutation in an infertile male resulting in the substitution of histidine for proline at position 398 of the protein sequence (PLCζ(H398P)), leading to abnormal PLCζ function and infertility. METHODS AND RESULTS: Here, using a combination of direct-sequencing and mini-sequencing of the PLCζ gene from the patient and his family, we report the identification of a second PLCζ mutation in the same patient resulting in a histidine to leucine substitution at position 233 (PLCζ(H233L)), which is predicted to disrupt local protein interactions in a manner similar ...
... δ-1 Phosphatidylinositol-specific phospholipase C Identifiers Symbol PI-PLC-X Pfam PF00388 InterPro IPR000909 SMART PLCXc SCOP
The phospholipase D3 (PLD3 ) gene has shown association with Alzheimers disease (AD). However, the role of PLD3 common variants in amyloid-β (Aβ ) pathology remains unclear. We examined the association of thirteen common single nucleotide polymorphi
In this work we compared the effect of five heavy metals: Zn, Pb, Cd, Ni and Cu on phospholipid composition of the ubiquitous soil fungus Paecilomyces marquandii, originating from a strongly metal polluted area and characterized by high tolerance to these elements. Cd, Ni and Cu caused an increase in phosphatidylcholine (PC). Only Pb decreased PC content, which was accompanied by a significant rise in the phosphatidic acids (PA) level, probably due to activation of phospholipase D which hydrolyzes PC to PA. This could result in membrane fluidity disturbance, and thus affect its integrity. The assessment of propidium iodide influx showed strong disturbance of membrane integrity for Cu and Pb stressed mycelia, whereas mycelia treated with Ni were impermeable to this dye. The results obtained revealed a strong Cu and Pb toxicity involving disruption of membrane integrity. Pb action was reflected by lipid composition, whereas ...
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LysoPC(22:1(13Z)) is a lysophospholipid (LyP). It is a monoglycerophospholipid in which a phosphorylcholine moiety occupies a glycerol substitution site. Lysophosphatidylcholines can have different combinations of fatty acids of varying lengths and saturation attached at the C-1 (sn-1) position. Fatty acids containing 16, 18 and 20 carbons are the most common. LysoPC(22:1(13Z)), in particular, consists of one chain of erucic acid at the C-1 position. The erucic acid moiety is derived from seed oils and avocados. Lysophosphatidylcholine is found in small amounts in most tissues. It is formed by hydrolysis of phosphatidylcholine by the enzyme phospholipase A2, as part of the de-acylation/re-acylation cycle that controls its overall molecular species composition. It can also be formed inadvertently during extraction of lipids from tissues if the phospholipase is activated by careless handling. In blood plasma significant amounts of ...
LysoPC(16:1(9Z)) is a lysophospholipid (LyP). It is a monoglycerophospholipid in which a phosphorylcholine moiety occupies a glycerol substitution site. Lysophosphatidylcholines can have different combinations of fatty acids of varying lengths and saturation attached at the C-1 (sn-1) position. Fatty acids containing 16, 18 and 20 carbons are the most common. LysoPC(16:1(9Z)), in particular, consists of one chain of palmitoleic acid at the C-1 position. Lysophosphatidylcholine is found in small amounts in most tissues. It is formed by hydrolysis of phosphatidylcholine by the enzyme phospholipase A2, as part of the de-acylation/re-acylation cycle that controls its overall molecular species composition. It can also be formed inadvertently during extraction of lipids from tissues if the phospholipase is activated by careless handling ...
Definition : Immunoassay reagents intended to perform quantitative analyses of body fluids (typically plasma or serum) to determine the level of the lipoprotein-associated enzyme phospholipase A2 (Lp-PLA2). These tests are usually based on turbidimetric or ELISA tests that use specific antibodies to identify the level of (Lp-PLA2). They may be used as an aid to assess vascular inflammation and the risk for coronary heart disease and ischemic stroke associated with atherosclerosis.. Entry Terms : "Lipoprotein-Associated Phospholipase A2 Determination Reagents" , "Lp-PLA2 Determination Reagents" , "PLAC Test ELISA Kits" , "PLAC Test Reagent Kits". UMDC code : 32900 ...
Phospholipase C gamma 1 ELISA Kits für viele Reaktivitäten. Huhn, Rind (Kuh), Hund und weitere. Phospholipase C gamma 1 ELISA Kits vergleichen und bestellen.
... is a member of the synuclein family, which also includes beta- and gamma-synuclein. Synucleins are abundantly expressed in the brain and alpha- and beta-synuclein inhibit phospholipase D2 selectively. SNCA may serve to integrate presynaptic signaling and membrane trafficking. Defects in SNCA have been implicated in the pathogenesis of Parkinson disease. SNCA peptides are a major component of amyloid plaques in the brains of patients with Alzheimers disease. Alternatively spliced transcripts encoding different isoforms have been identified for this gene. [provided by RefSeq, Feb 2016 ...
There is a great need of improved anticancer drugs and corresponding drug carriers. In particular, liposomal drug carriers with heat-activated release and targeting functions are being developed for combined hyperthermia and chemotherapy treatments of tumors. The aim of this study is to demonstrate the heat-activation of liposome targeting to biotinylated surfaces, in model experiments where streptavidin is used as a pretargeting protein. The design of the heat-activated liposomes is based on liposomes assembled in an asymmetric structure and with a defined phase transition temperature. Asymmetry between the inside and the outside of the liposome membrane was generated through the enzymatic action of phospholipase D, where lipid head groups in the outer membrane leaflet, i.e. exposed to the enzyme, were hydrolyzed. The enzymatically treated and purified liposomes did not bind to streptavidin-modified surfaces. When activation heat was ...
Academic Dissertations;Academic Dissertations--South Carolina;Focal Adhesion Protein-Tyrosine Kinases;Mitogens;Focal Adhesion Kinase 1;Phospholipase D;Cell ...
Biosynthesis of TxA2 and the PG involves the sequential metabolism of AA in three stages. The first rate-limiting step is the stimulus-induced mobilization of AA from cell membrane phosphoglycerides by the enzymes phospholipase (PL) A2 (acting on phosphatidylcholine) and diacylglycerol (DAG) lipase (acting on phosphatidylinositol). The second is the oxidation of AA to the PG endoperoxides by the enzyme PG endoperoxide synthase, also known as cyclooxygenase (COX). This involves two sequential actions by the enzyme: first, the conversion of AA to endoperoxide PGG2 (COX activity), and, subsequently, the conversion of PGG2 to endoperoxide PGH2 (peroxidase activity). In the third and final stage, PGH2 is isomerized into the biologically active prostanoid end products by specific PG synthase enzymes (9, 59, 71). For TxA2 biosynthesis, this involves the action of TxA2 synthase (TxS) on PGH2 to produce TxA2. The profile of prostanoid end products produced within ...
Shop Group 10 secretory phospholipase ELISA Kit, Recombinant Protein and Group 10 secretory phospholipase Antibody at MyBioSource. Custom ELISA Kit, Recombinant Protein and Antibody are available.
DAVID W. STANLEYserves as Supervisory Research Entomologist and Research Leader. His research is connected to each of the three main projects in the BCIRL. Relative to the nutrition project, certain fatty acids are essential nutrients for insects. These components must be digested before insects can assimilate them. The enzyme phospholipase A2 is crucial in lipid digestion and research in this area is designed to test the idea that this enzyme may be a novel target for improving biocontrol of pest insects. In the immunology project, research is aimed at discovery and understanding of signal mechanisms (particularly prostaglandin systems) responsible for mediating and coordinating pest insect immune reactions to biological control agents. This research is revealing new enzymes and receptors that may be exploited in integrated biocontrol efforts. In the cell culture/virology area, the main goal is to understand cellular defense reactions to viral infection. Current work uses ...
The ability of lysoPC, either independently or as a component of oxidized LDL, to inhibit endothelial-dependent vasorelaxation is well established (Cowan and Steffen, 1995; Freeman et al., 1996). The effect of lysoPC to impair endothelium-dependent relaxation is generalized to a variety of endothelium-dependent vasodilators, including acetylcholine (Kugiyama et al., 1990), 5-hyroxytryptamine (Cox and Cohen, 1996a), thrombin (Murohara et al., 1994) and calcium ionophore A23187 (Mangin et al., 1993). However, the cellular pathways affected by lysoPC that ultimately result in endothelial vasomotor dysfunction remain unclear. LysoPC was recently documented to stimulate PLD activity in cultured human endothelial cells (Cox and Cohen, 1996c), although the role of this effect in the vasomotor actions of lysoPC was not addressed. The present study has demonstrated the ability of lysoPC to stimulate vascular PLD activity in isolated blood vessels and has documented a close association between the ability ...
... , Authors: Matilde Y. Follo, Vincenza Rita Lo Vasco, Giovanni Martinelli, Giandomenico Palka, Lucio Cocco. Published in: Atlas Genet Cytogenet Oncol Haematol.
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middle aged woman loses her husband and only son to battle pandora bracciali outlet, high definition channels. But you want more variety of programming outside the your local broadcasts. One of the most popular and simple options is to connect an Apple TV to your television. Work from the top of the wall down. Smooth on the mud verticallybut their pride is searching for an excuse to oppose you. The latest leak also shows desktop style context menus for Metro tiles. Right clicking on tiles apparently brings up a mouse friendly menu rather than the app bar at the bottom of the screen. According to Windows guru Paul Thurrot sconti bracciali pandora etc. There is no practical end to the list. You dont even know how to talk properly because your mind is on leave. Yet most of the time you feel just fine without company. Aloneness is rich and meditative and seldom lonely. A: This is a scale business. Rdios in 51 countries. Janus Friis who co founded Skype has spent close to $200 million on this ...
Phosphatidic acid influences the gating of voltage-gated K+ channels through a non-specific surface charge mechanism and through a specific interaction between a voltage sensor arginine and the primary phosphate head group on the cytoplasmic membrane leaflet.
최근 외부자극에 대한 생체 신호전달체계에서 중요한 효소로 알려진 phospholipase C(PLC) 동위효소(isozyme)들의 발현은 조직의 종류와 발달과정에 따라 특이한 양상을 보이며 PLC동위효소 중 PLC-γ1은 세포의 성장, 분화 및 증식에 중추적 요소로 알려져 있다. 또한 ras 암유전자단백도 세포의 성장을 유도하는 것으로 알려져 있어 방사선 조사 후 PLC 동위효소와 ras암유전단백이 관여하는지를 규명하고, 이러한 재생과정에 방사선감작약물로 널리 알려져 있는 5-fluorouracil(5-FU)투여방법이 미치는 영향을 보고자 본 연구를 계획하였다. 흰쥐를 실험동물로 하여 정상대조군(I), 방사선조사 단독군(II), 방사선과 5-FU 12시간 지속성 정주병행군(III), 방사선조사 단독군 (II), 방사선과 5-FU12시간 지속성 정주단독군 (V), 5FU 일시정주단독군 (VI)로 나누어 관찰하였다. 방사선은 흰쥐 ...
Reaktivität: Huhn, Rind (Kuh), Hund and more. 12 verschiedene PIPLC ELISA Kits vergleichen. Alle direkt auf antikoerper-online.de bestellbar!
Eicosanoid biosynthesis begins when cell is activated by mechanical trauma, cytokines, growth factors or other stimuli. (The stimulus may even be an eicosanoid from a neighboring cell; the pathways are complex.) This triggers the release of a phospholipase at the cell membrane. The phospholipase travels to the nuclear membrane. There, the phospholipase catalyzes ester hydrolysis of phospholipid (by A2) or diacylglycerol (by phospholipase C). This frees a 20-carbon essential fatty acid. This hydrolysis appears to be the rate-determining step for eicosanoid formation free fatty acid is oxygenated along any of several pathways ...
Eicosanoid biosynthesis begins when cell is activated by mechanical trauma, cytokines, growth factors or other stimuli. (The stimulus may even be an eicosanoid from a neighboring cell; the pathways are complex.) This triggers the release of a phospholipase at the cell membrane. The phospholipase travels to the nuclear membrane. There, the phospholipase catalyzes ester hydrolysis of phospholipid (by A2) or diacylglycerol (by phospholipase C). This frees a 20-carbon essential fatty acid. This hydrolysis appears to be the rate-determining step for eicosanoid formation free fatty acid is oxygenated along any of several pathways ...
Catalyzes the hydrolysis of phosphatidylcholine with phospholipase A1 (EC 3.1.1.32) activity (PubMed:14572904). Shows hemolytic activity (By similarity).
In A549, Bel-7402, MCF-7 and LLC cell lines, acetylshikonin inhibited cell growth in a dose-dependent manner. IC50 (means ± SD) were 5.6 ± 0.86 μg/ml, 6.82 ± 1.5 μg/ml, 3.04 ± 0.44 μg/ml and 2.72 ± 0.38 μg/ml respectively. Acetylshikonin suppressed tumor growth in C57BL/6 mice with LLC. The inhibition rate of acetylshikonin (2 mg/kg) was 42.85%. Immunohistochemical staining revealed that in the acetylshikonin groups the expression of bax and caspase-3 increased, whereas the expression of bcl-2 decreased, suggesting that acetylshikonin induced tumor cell apoptosis through activating the pro-apoptotic bcl-2 family and caspase-3 ...
phospholipase B-lipase: a rat intestinal enzyme associated with brush border membranes; has PLA2, lysophospholipase & lipase activities; amino acid sequence in first source; GenBank D63648
3V16: Structure of the S. aureus PI-Specific Phospholipase C Reveals Modulation of Active Site Access by a Titratable PI-Cation Latched Loop
1-(5-Bromo-2-fluorophenyl)butan-1-one/AFI1197943615 can be provided in Alfa Chemistry. We are dedicated to provide our customers the best products and services.
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Recently they changed their kitchen and now make the rice and veggies fresh at the school, and offer two choices a Meat Set with two meat dishes and a Vegetarian Set with one vegetarian dish. Both are served with rice and veggies. There are no repeated options in the month - which is pretty impressive! I have to order a month in advance, and the cost is about 18 HKD a day (2.30 USD) (Ill add a link or photo to a sample monthly menu from the school when I get it next month ...
Complete information for PLCXD3 gene (Protein Coding), Phosphatidylinositol Specific Phospholipase C X Domain Containing 3, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
Downloadable! This paper examines the determinants of young innovative companies (YICs) R&D activities taking into account the autoregressive nature of innovation. Using a large longitudinal dataset comprising Spanish manufacturing firms over the period 1990-2008, we find that previous R&D experience is a fundamental determinant for mature and young firms, albeit to a smaller extent in the case of the YICs, suggesting that their innovation behaviour is less persistent and more erratic. Moreover, our results suggest that firm and market characteristics play a distinct role in boosting the innovation activity of firms of different age. In particular, while market concentration and the degree of product diversification are found to be important in boosting R&D activities in the sub-sample of mature firms only, YICs spending on R&D appears to be more sensitive to demand-pull variables, suggesting the presence of credit constraints. These results have been obtained using a recently proposed dynamic type-2
Mouse polyclonal antibody raised against a partial recombinant PLD2. PLD2 (AAH15033, 834 a.a. ~ 933 a.a) partial recombinant protein with GST tag. (H00005338-A01) - Products - Abnova
1CEH: Structure and function of the catalytic site mutant Asp 99 Asn of phospholipase A2: absence of the conserved structural water.

Cerebrospinal fluid secretory [Ca.sup.2+]-dependent phospholipase [A.sub.2] activity is increased in alzheimer disease. - Free...Cerebrospinal fluid secretory [Ca.sup.2+]-dependent phospholipase [A.sub.2] activity is increased in alzheimer disease. - Free...

... dependent phospholipase [A.sub.2] activity is increased in alzheimer disease.(Proteomics and Protein Markers) by Clinical ... Slow- and tight-binding inhibitors of the 85-kDa human phospholipase [A.sub.2]. Biochemistry 1993;32:5935-40. (14.) Plesniak LA ... Elevated CSF prostaglandin E2 levels in patients with probable AD. Neurology 1999;53:1495-8. (39.) Montine TJ, Beal MF, ... regulation of gene expression and maintenance of neural membrane integrity, and serve as precursors for the synthesis of ...
more infohttps://www.thefreelibrary.com/Cerebrospinal+fluid+secretory+%5BCa.sup.2%2B%5D-dependent+phospholipase+...-a0324398243

An Essential Role of Cytosolic Phospholipase A2α in Prostaglandin E2-mediated Bone Resorption Associated with Inflammation | JEMAn Essential Role of Cytosolic Phospholipase A2α in Prostaglandin E2-mediated Bone Resorption Associated with Inflammation | JEM

... membrane-bound prostaglandin E synthase; PG, prostaglandin; PGE, prostaglandin E; PGES, PGE synthase; PLA2, phospholipase A2; ... Regulation of prostaglandin E2 biosynthesis by inducible membrane-associated prostaglandin E2 synthase that acts in concert ... An Essential Role of Cytosolic Phospholipase A2α in Prostaglandin E2-mediated Bone Resorption Associated with Inflammation. ... Osteoblastic bone marrow stromal cells induced the expression of cyclooxygenase (COX)-2 and membrane-bound PGE2 synthase (mPGES ...
more infohttp://jem.rupress.org/content/197/10/1303

Glucocorticoids inhibit prostaglandin synthesis not only at the level of phospholipase A2 but also at the level of cyclo...Glucocorticoids inhibit prostaglandin synthesis not only at the level of phospholipase A2 but also at the level of cyclo...

2Endogenous membrane bound phospholipase A2 was measured with labelled phospholipids used as substrates. The enzyme activity ... Glucocorticoids inhibit prostaglandin synthesis not only at the level of phospholipase A2 but also at the level of cyclo- ... 3The enzyme activity of the cyclo-oxygenase/prostaglandin E (PGE) isomerase was measured in cell membranes from control cells ... When the cells were preincubated with dexamethasone (10−7 and 10−6m) overnight, prostaglandin synthesis was inhibited by 66.5 ...
more infohttp://onlinelibrary.wiley.com/doi/10.1111/j.1476-5381.1989.tb12676.x/abstract

Brain Sciences  | Free Full-Text | Ethanol Neurotoxicity in the Developing Cerebellum: Underlying Mechanisms and Implications |...Brain Sciences | Free Full-Text | Ethanol Neurotoxicity in the Developing Cerebellum: Underlying Mechanisms and Implications |...

In prostaglandin synthesis, the enzyme phospholipase A2 (PLA2) catalyzes the formation of arachidonic acid from membrane-bound ... 9. Ethanol Increases Prostaglandin Production. Prostaglandins (PGs), especially prostaglandin E2 (PGE2), regulate CNS ... Binding of BDNF to its receptor, TrkB, activates the MAP kinase, phospholipase C-γ (PLC-γ) and PI3-kinase pathways, and ... Retinoic acid binds to intracellular binding proteins then translocates to the nucleus. In the nucleus, RA acts as a ligand for ...
more infohttp://mdpi.com/2076-3425/3/2/941/htm

Mechanisms of Decreased Vascular Function With Aging | HypertensionMechanisms of Decreased Vascular Function With Aging | Hypertension

... from membrane-bound phospholipids, which is then available for metabolism by COX. Prostaglandin H2 (PGH2) is generated via the ... Also in the endothelial cell, elevated intracellular Ca++ and PKs activate phospholipase A2 (PLA2). Activated PLA2 liberates ... Other prostaglandins, eg, prostaglandin E2 (PGE2), prostaglandin D2 (PGD2), and prostaglandin F2α (PGF2α), are also formed. PGI ... Endothelial NO and prostaglandin vasodilator pathways. Endothelial agonists, eg, acetylcholine (Ach), substance P (subs P), and ...
more infohttp://hyper.ahajournals.org/content/53/6/900

Phospholipase A2: A Potential Therapeutic Target in Inflammation and Cancer (In silico, In vitro, In vivo and Clinical Approach...Phospholipase A2: A Potential Therapeutic Target in Inflammation and Cancer (In silico, In vitro, In vivo and Clinical Approach...

Phospholipase A2 (PLA2) (EC 3.1.1.4) is the initial enzyme of arachidonic acid cascade, has key role in inflammation and cancer ... Phospholipase A2 (PLA2) (EC 3.1.1.4) are group of enzymes, which specifically recognizes the sn-2 acyl bond of membrane bound ... ElAttar TM, Lin HS, Shultz R (1988) Effect of minocycline on prostaglandin formation in gingival fibroblasts.J Periodontal Res ... Lysosomal phospholipase A2 (GXV LPLA2) and Adipose specific phospholipase A2 (GXVI ADPLA) are other types of the PLA2 ...
more infohttps://www.omicsonline.org/open-access/phospholipase-a2-a-potential-therapeutic-target-in-inflammation-and-cancer-in-silico-in-vitro-in-vivo-and-clinical-approach-1948-5956-1000357.php?aid=57701

Cortisone acetate - DrugBankCortisone acetate - DrugBank

... whereas all of them bind albumin. Glucocorticoids also bind to the cytosolic glucocorticoid receptor. ... which then binds to cell membranes preventing the phospholipase A2 from coming into contact with its substrate arachidonic acid ... In other words, the two main products in inflammation Prostaglandins and Leukotrienes are inhibited by the action of ... corticosteroid-binding protein), whereas all of them bind albumin. Glucocorticoids also bind to the cytosolic glucocorticoid ...
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The low molecular weight fraction of human serum albumin upregulates COX2, prostaglandin E2, and prostaglandin D2 under...The low molecular weight fraction of human serum albumin upregulates COX2, prostaglandin E2, and prostaglandin D2 under...

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  • Inflammation is diminished by decreasing the discharge of leukocytic acid hydrolases, prevention of macrophage accumulation at inflamed sites, interference with leukocyte adhesion to the capillary wall, reduction of capillary membrane permeability, reduction of complement elements, inhibition of histamine and kinin release, and interference with the formation of connective tissue. (reliablerxpharmacy.com)
  • The inner and outer surfaces, or interfacial regions, of model phospholipid bilayers have been shown to have a thickness of around 8 to 10 Å, although this may be wider in biological membranes that include large amounts of gangliosides or lipopolysaccharides. (wikipedia.org)
  • The hydrophobic inner core region of typical biological membranes may have a thickness of around 27 to 32 Å, as estimated by Small angle X-ray scattering (SAXS). (wikipedia.org)
  • There his interests shifted to biological membranes, a research area that occupied him for the rest of his life. (asbmb.org)
  • In 1980, he coauthored a textbook, "Introduction to Biological Membranes," with Roger Wagner in the biological science department at the University of Delaware. (asbmb.org)
  • Membrane binding may also promote rearrangement, dissociation, or conformational changes within many protein structural domains, resulting in an activation of their biological activity. (wikipedia.org)
  • It also may involve the formation or dissociation of protein quaternary structures or oligomeric complexes, and specific binding of ions, ligands, or regulatory lipids. (wikipedia.org)
  • The site allows visualization of protein structures with membrane boundary planes through Jmol . (wikipedia.org)
  • The phospholipid bilayer that forms the cell surface membrane consists of a hydrophobic inner core region sandwiched between two regions of hydrophilicity, one at the inner surface and one at the outer surface of the cell membrane (see lipid bilayer article for a more detailed structural description of the cell membrane). (wikipedia.org)
  • It was during that time that he wrote a book, "The Bimolecular Lipid Membrane: a System," published by Van Nostrand Reinhold Co. in 1972. (asbmb.org)
  • Mast cells also produce new products (secondary mediators) via a series of reac- tions within the cell membrane that lead to the generation of lipid media- tors and cytokines buy discount kamagra chewable 100mg online erectile dysfunction 42. (easyhyperlinks.com)
  • In this study, we investigated the effects of the low molecular weight fraction of 5% human serum albumin (LMWF-5A), an agent that has proven to decrease pain and improve function in OAK patients after intra-articular injection, on the expression of COX2 and its downstream products, prostaglandins (PGs). (pubmedcentralcanada.ca)
  • Conclusions -The EETs thus formed will be released and activate K + channels, increase outward K + current, and hyperpolarize the plasma membrane. (ahajournals.org)
  • Mast cells have secretory granules that fuse to the cytoplasmic membrane and release their contents outside. (blogspot.com)
  • The resulting membrane hyperpolarization inhibits voltage-gated Ca 2+ channels and leads to arteriolar dilation, thereby increasing regional nutritive blood flow in response to neuronal activity. (ahajournals.org)