Lipoxygenase
Arachidonate 5-Lipoxygenase
Arachidonate 12-Lipoxygenase
Lipoxygenase Inhibitors
Arachidonate 15-Lipoxygenase
Arachidonate Lipoxygenases
Enzymes catalyzing the oxidation of arachidonic acid to hydroperoxyarachidonates. These products are then rapidly converted by a peroxidase to hydroxyeicosatetraenoic acids. The positional specificity of the enzyme reaction varies from tissue to tissue. The final lipoxygenase pathway leads to the leukotrienes. EC 1.13.11.- .
12-Hydroxy-5,8,10,14-eicosatetraenoic Acid
A lipoxygenase metabolite of ARACHIDONIC ACID. It is a highly selective ligand used to label mu-opioid receptors in both membranes and tissue sections. The 12-S-HETE analog has been reported to augment tumor cell metastatic potential through activation of protein kinase C. (J Pharmacol Exp Ther 1995; 274(3):1545-51; J Natl Cancer Inst 1994; 86(15):1145-51)
Leukotrienes
A family of biologically active compounds derived from arachidonic acid by oxidative metabolism through the 5-lipoxygenase pathway. They participate in host defense reactions and pathophysiological conditions such as immediate hypersensitivity and inflammation. They have potent actions on many essential organs and systems, including the cardiovascular, pulmonary, and central nervous system as well as the gastrointestinal tract and the immune system.
Masoprocol
Hydroxyeicosatetraenoic Acids
5-Lipoxygenase-Activating Proteins
Arachidonic Acid
An unsaturated, essential fatty acid. It is found in animal and human fat as well as in the liver, brain, and glandular organs, and is a constituent of animal phosphatides. It is formed by the synthesis from dietary linoleic acid and is a precursor in the biosynthesis of prostaglandins, thromboxanes, and leukotrienes.
Leukotriene B4
4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine
5,8,11,14-Eicosatetraynoic Acid
Leukotriene A4
(2S-(2 alpha,3 beta(1E,3E,5Z,8Z)))-3-(1,3,5,8-Tetradecatetraenyl)oxiranebutanoic acid. An unstable allylic epoxide, formed from the immediate precursor 5-HPETE via the stereospecific removal of a proton at C-10 and dehydration. Its biological actions are determined primarily by its metabolites, i.e., LEUKOTRIENE B4 and cysteinyl-leukotrienes. Alternatively, leukotriene A4 is converted into LEUKOTRIENE C4 by glutathione-S-transferase or into 5,6-di-HETE by the epoxide-hydrolase. (From Dictionary of Prostaglandins and Related Compounds, 1990)
Eicosanoids
SRS-A
A group of LEUKOTRIENES; (LTC4; LTD4; and LTE4) that is the major mediator of BRONCHOCONSTRICTION; HYPERSENSITIVITY; and other allergic reactions. Earlier studies described a "slow-reacting substance of ANAPHYLAXIS" released from lung by cobra venom or after anaphylactic shock. The relationship between SRS-A leukotrienes was established by UV which showed the presence of the conjugated triene. (From Merck Index, 11th ed)
Lipid Peroxides
Peroxides produced in the presence of a free radical by the oxidation of unsaturated fatty acids in the cell in the presence of molecular oxygen. The formation of lipid peroxides results in the destruction of the original lipid leading to the loss of integrity of the membranes. They therefore cause a variety of toxic effects in vivo and their formation is considered a pathological process in biological systems. Their formation can be inhibited by antioxidants, such as vitamin E, structural separation or low oxygen tension.
Linoleic Acid
Lipoxins
Calcimycin
An ionophorous, polyether antibiotic from Streptomyces chartreusensis. It binds and transports CALCIUM and other divalent cations across membranes and uncouples oxidative phosphorylation while inhibiting ATPase of rat liver mitochondria. The substance is used mostly as a biochemical tool to study the role of divalent cations in various biological systems.
Cyclooxygenase Inhibitors
Indomethacin
Chromatography, High Pressure Liquid
Soybeans
Leukotriene Antagonists
Prostaglandin-Endoperoxide Synthases
Hydroxyurea
Leukotriene C4
The conjugation product of LEUKOTRIENE A4 and glutathione. It is the major arachidonic acid metabolite in macrophages and human mast cells as well as in antigen-sensitized lung tissue. It stimulates mucus secretion in the lung, and produces contractions of nonvascular and some VASCULAR SMOOTH MUSCLE. (From Dictionary of Prostaglandins and Related Compounds, 1990)
Neutrophils
Phospholipases A
Receptors, Leukotriene
Phospholipases A2
Caffeic Acids
Leukocytes
Leukotriene E4
Blood Platelets
Benzeneacetamides
Fatty Acids, Unsaturated
Reticulocytes
Immature ERYTHROCYTES. In humans, these are ERYTHROID CELLS that have just undergone extrusion of their CELL NUCLEUS. They still contain some organelles that gradually decrease in number as the cells mature. RIBOSOMES are last to disappear. Certain staining techniques cause components of the ribosomes to precipitate into characteristic "reticulum" (not the same as the ENDOPLASMIC RETICULUM), hence the name reticulocytes.
8,11,14-Eicosatrienoic Acid
Epoxide Hydrolases
Pyrazoles
Receptors, Leukotriene B4
A class of cell surface leukotriene receptors with a preference for leukotriene B4. Leukotriene B4 receptor activation influences chemotaxis, chemokinesis, adherence, enzyme release, oxidative bursts, and degranulation in polymorphonuclear leukocytes. There are at least two subtypes of these receptors. Some actions are mediated through the inositol phosphate and diacylglycerol second messenger systems.
Thromboxane B2
Oxylipins
Oxidation-Reduction
A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471).
Cucumis sativus
Rabbits
Lipoxygenases
Autacoids
Quinacrine
Dinoprostone
Cells, Cultured
Peroxides
A group of compounds that contain a bivalent O-O group, i.e., the oxygen atoms are univalent. They can either be inorganic or organic in nature. Such compounds release atomic (nascent) oxygen readily. Thus they are strong oxidizing agents and fire hazards when in contact with combustible materials, especially under high-temperature conditions. The chief industrial uses of peroxides are as oxidizing agents, bleaching agents, and initiators of polymerization. (From Hawley's Condensed Chemical Dictionary, 11th ed)
Stereoisomerism
Solanum tuberosum
Molecular Sequence Data
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
Benzoquinones
Substrate Specificity
Cyclooxygenase 2
Enzyme Activation
RNA, Messenger
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
5-Lipoxygenase-Activating Protein Inhibitors
Indoles
Leukotriene D4
One of the biologically active principles of SRS-A. It is generated from LEUKOTRIENE C4 after partial hydrolysis of the peptide chain, i.e., cleavage of the gamma-glutamyl portion. Its biological actions include stimulation of vascular and nonvascular smooth muscle, and increases in vascular permeability. (From Dictionary of Prostaglandins and Related Compounds, 1990)
Receptors, Eicosanoid
Gas Chromatography-Mass Spectrometry
Platelet Activating Factor
Intramolecular Oxidoreductases
Enzymes of the isomerase class that catalyze the oxidation of one part of a molecule with a corresponding reduction of another part of the same molecule. They include enzymes converting aldoses to ketoses (ALDOSE-KETOSE ISOMERASES), enzymes shifting a carbon-carbon double bond (CARBON-CARBON DOUBLE BOND ISOMERASES), and enzymes transposing S-S bonds (SULFUR-SULFUR BOND ISOMERASES). (From Enzyme Nomenclature, 1992) EC 5.3.
Prostaglandins
Nonheme Iron Proteins
Umbelliferones
7-Hydroxycoumarins. Substances present in many plants, especially umbelliferae. Umbelliferones are used in sunscreen preparations and may be mutagenic. Their derivatives are used in liver therapy, as reagents, plant growth factors, sunscreens, insecticides, parasiticides, choleretics, spasmolytics, etc.
Isoenzymes
Dose-Response Relationship, Drug
Enzyme Inhibitors
Dioctyl Sulfosuccinic Acid
Anti-Inflammatory Agents, Non-Steroidal
Anti-inflammatory agents that are non-steroidal in nature. In addition to anti-inflammatory actions, they have analgesic, antipyretic, and platelet-inhibitory actions.They act by blocking the synthesis of prostaglandins by inhibiting cyclooxygenase, which converts arachidonic acid to cyclic endoperoxides, precursors of prostaglandins. Inhibition of prostaglandin synthesis accounts for their analgesic, antipyretic, and platelet-inhibitory actions; other mechanisms may contribute to their anti-inflammatory effects.
Base Sequence
Cytosol
Prostaglandins E
(11 alpha,13E,15S)-11,15-Dihydroxy-9-oxoprost-13-en-1-oic acid (PGE(1)); (5Z,11 alpha,13E,15S)-11,15-dihydroxy-9-oxoprosta-5,13-dien-1-oic acid (PGE(2)); and (5Z,11 alpha,13E,15S,17Z)-11,15-dihydroxy-9-oxoprosta-5,13,17-trien-1-oic acid (PGE(3)). Three of the six naturally occurring prostaglandins. They are considered primary in that no one is derived from another in living organisms. Originally isolated from sheep seminal fluid and vesicles, they are found in many organs and tissues and play a major role in mediating various physiological activities.
Pleurisy
Gene Expression Regulation, Enzymologic
Pyrazolones
Chromatography, Thin Layer
Amino Acid Sequence
Membrane Proteins
Spectrophotometry, Ultraviolet
Macrophages
The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.)
Calcium
A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.
Seeds
Cyclooxygenase 1
Ionophores
Chemical agents that increase the permeability of biological or artificial lipid membranes to specific ions. Most ionophores are relatively small organic molecules that act as mobile carriers within membranes or coalesce to form ion permeable channels across membranes. Many are antibiotics, and many act as uncoupling agents by short-circuiting the proton gradient across mitochondrial membranes.
Eicosapentaenoic Acid
Important polyunsaturated fatty acid found in fish oils. It serves as the precursor for the prostaglandin-3 and thromboxane-3 families. A diet rich in eicosapentaenoic acid lowers serum lipid concentration, reduces incidence of cardiovascular disorders, prevents platelet aggregation, and inhibits arachidonic acid conversion into the thromboxane-2 and prostaglandin-2 families.
Monocytes
Reactive oxygen intermediate-dependent NF-kappaB activation by interleukin-1beta requires 5-lipoxygenase or NADPH oxidase activity. (1/135)
We previously reported that the role of reactive oxygen intermediates (ROIs) in NF-kappaB activation by proinflammatory cytokines was cell specific. However, the sources for ROIs in various cell types are yet to be determined and might include 5-lipoxygenase (5-LOX) and NADPH oxidase. 5-LOX and 5-LOX activating protein (FLAP) are coexpressed in lymphoid cells but not in monocytic or epithelial cells. Stimulation of lymphoid cells with interleukin-1beta (IL-1beta) led to ROI production and NF-kappaB activation, which could both be blocked by antioxidants or FLAP inhibitors, confirming that 5-LOX was the source of ROIs and was required for NF-kappaB activation in these cells. IL-1beta stimulation of epithelial cells did not generate any ROIs and NF-kappaB induction was not influenced by 5-LOX inhibitors. However, reintroduction of a functional 5-LOX system in these cells allowed ROI production and 5-LOX-dependent NF-kappaB activation. In monocytic cells, IL-1beta treatment led to a production of ROIs which is independent of the 5-LOX enzyme but requires the NADPH oxidase activity. This pathway involves the Rac1 and Cdc42 GTPases, two enzymes which are not required for NF-kappaB activation by IL-1beta in epithelial cells. In conclusion, three different cell-specific pathways lead to NF-kappaB activation by IL-1beta: a pathway dependent on ROI production by 5-LOX in lymphoid cells, an ROI- and 5-LOX-independent pathway in epithelial cells, and a pathway requiring ROI production by NADPH oxidase in monocytic cells. (+info)Relationship of arachidonic acid metabolizing enzyme expression in epithelial cancer cell lines to the growth effect of selective biochemical inhibitors. (2/135)
Arachidonic acid (AA) metabolizing enzymes are emerging as significant mediators of growth stimulation for epithelial cells. The relative contribution of the various family members of AA metabolizing enzymes to epithelial cancer cell growth is not known. To study this question, we first analyzed a series of epithelial cancer cells to establish the relative frequency of expression for the various enzymes. We analyzed the expression of five AA metabolizing enzymes as well as 5-lipoxygenase activating protein (FLAP) in a panel of human epithelial cancer cell lines (n = 20) using reverse transcription-PCR. From this analysis, we found that cyclooxygenase-1 (COX-1), 5-lipoxygenase (5-LOX), and FLAP were universally expressed in all cancer cell lines tested. For the remaining enzymes, the expression of COX-2, 12-LOX, and 15-LOX varied among cell lines, 60, 35, and 90%, respectively. Although the pattern of expression varied among the different cell types, all of the enzymes were expressed in all major cancer histologies. Using a panel of selective biochemical AA metabolizing enzyme inhibitors, we then evaluated the effect of these agents on cell lines with known expression status for the AA metabolizing enzymes. For the enzymes that were not universally expressed, growth inhibition by selective biochemical inhibitors did not closely correlate with the expression status of specific enzymes (P > 0.05). For the universally expressed enzymes, the LOX inhibitors were more potent growth inhibitors than the COX inhibitors. The frequent expression of the AA metabolizing enzymes suggests that AA metabolism pathway may be modulated in response to xenobiotic exposure during carcinogenesis. Although establishing a priori AA metabolizing enzyme status was not consistently informative about what AA metabolizing enzyme inhibition would be most growth inhibitory, the frequent inhibition of many epithelial cancers by these biochemical inhibitors opens a new avenue for cancer therapy and intervention in carcinogenesis. (+info)The 5-lipoxygenase-activating protein (FLAP) inhibitor, MK886, induces apoptosis independently of FLAP. (3/135)
The ability of various inhibitors of lipoxygenase (LOX) enzymes and 5-lipoxygenase-activating protein (FLAP) to induce apoptosis has implicated these pathways in the mechanism(s) of this form of cell death. Although FLAP plays an important role in 5-LOX activity, this protein is found at high levels in some cells lacking LOX, suggesting it might mediate other effects. Furthermore, the concentration of MK886, a FLAP inhibitor, required to induce apoptosis is approximately 100-fold more than that required to inhibit LOX, and this compound remains effective in cells lacking LOX. The present study examines the role of FLAP in MK886-induced apoptosis. MK886 induced apoptosis in WSU cells, a human chronic lymphocytic leukaemia cell line that lacks FLAP protein and mRNA, suggesting that this agent is acting independently of FLAP. This conclusion was further supported by the fact that a more specific FLAP inhibitor, MK591, induced only minimal apoptosis in FL5.12 cells, a murine prolymphoid cell line containing FLAP. The role of FLAP was examined more directly by decreasing its expression by more than 50% in FL5.12 cells treated with 10 microM of an antisense oligonucleotide for 48h. This change in FLAP was not accompanied by any increase in apoptosis. Furthermore, FLAP-depleted cells exhibited the same level of apoptosis 8 h after treatment with 10 microM MK886, as did control cells. The increased fluorescence seen in MK886-treated cells loaded with carboxydichlorofluorescein indicates that oxidative reactions are stimulated by this compound, possibly via the release of fatty acids from fatty acid-binding proteins and their subsequent oxidation. (+info)Expression of 5-lipoxygenase and 5-lipoxygenase-activating protein in human fetal membranes throughout pregnancy and at term. (4/135)
Lipoxygenase metabolites may be involved in human parturition. 5-lipoxygenase (5-LOX) catalyses the first steps in the synthesis of leukotrienes from arachidonic acid, and its activity is dependent on 5-LOX activating protein (FLAP). The expression of 5-LOX and FLAP were investigated in fetal membranes to determine whether there are changes with gestational age or at term with the onset of labour. No significant differences were found in the expression of 5-LOX or FLAP mRNA in the amnion at different gestational ages or at term. In the chorion-decidua, 5-LOX mRNA expression was significantly higher in the first trimester of pregnancy than in the second and third trimesters. At term, there was a significant increase in both 5-LOX mRNA and protein expression in the chorion-decidua in the time after labour, compared with the time before labour. The expression of FLAP mRNA was also significantly higher in the chorion-decidua in the first trimester of pregnancy compared with the third trimester, and at term in the time after labour compared with the time before labour. Expression of FLAP protein was not studied, as an antibody is not currently available. These results are consistent with a role for 5-LOX and FLAP in the control of parturition at term, and also suggest an involvement earlier in pregnancy. (+info)IL-5 increases expression of 5-lipoxygenase-activating protein and translocates 5-lipoxygenase to the nucleus in human blood eosinophils. (5/135)
Cysteinyl-leukotrienes are potent bronchoconstrictor mediators synthesized by the 5-lipoxygenase (5-LO) pathway. Eosinophilopoietic cytokines such as IL-5 enhance cysteinyl-leukotriene synthesis in eosinophils in vitro, mimicking changes in eosinophils from asthmatic patients, but the mechanism is unknown. We hypothesized that IL-5 induces the expression of 5-LO and/or its activating protein FLAP in eosinophils, and that this might be modulated by anti-inflammatory corticosteroids. Compared with control cultures, IL-5 increased the proportion of normal blood eosinophils immunostaining for FLAP (65 +/- 4 vs 34 +/- 4%; p < 0.0001), enhanced immunoblot levels of FLAP by 51 +/- 14% (p = 0.03), and quadrupled ionophore-stimulated leukotriene C4 synthesis from 5.7 to 20.8 ng/106 cells (p < 0.02). IL-5 effects persisted for 24 h and were abolished by cycloheximide and actinomycin D. The proportion of FLAP+ eosinophils was also increased by dexamethasone (p < 0.0001). Neither IL-5 nor dexamethasone altered 5-LO expression, but IL-5 significantly increased 5-LO immunofluorescence localizing to eosinophil nuclei. Compared with normal subjects, allergic asthmatic patients had a greater proportion of circulating FLAP+ eosinophils (46 +/- 6 vs 27 +/- 3%; p < 0.03) and a smaller IL-5-induced increase in FLAP immunoreactivity (p < 0.05). Thus, IL-5 increases FLAP expression and translocates 5-LO to the nucleus in normal blood eosinophils in vitro. This is associated with an enhanced capacity for cysteinyl-leukotriene synthesis and mimics in vivo increases in FLAP expression in eosinophils from allergic asthmatics. (+info)Increased cyclooxygenase-2 and 5-lipoxygenase activating protein expression in peritoneal macrophages during ovalbumin immunization of mice and cytosolic phospholipase A(2) activation after antigen challenge. (6/135)
The present study investigates phenotypic and functional differentiation of peritoneal macrophages during ovalbumin-induced subcutaneous immunization of mice. For the first time we show that, in mouse peritoneal macrophages, ovalbumin immunization induces an increase in cyclooxygenase-2 (COX-2) and 5-lipoxygenase activating protein (FLAP) expression whereas it inhibits cytosolic phospholipase A(2) (cPLA2) expression. The study of arachidonic acid (AA) metabolism in peritoneal macrophages from control (cPM) and ovalbumin-immunized (iPM) mice shows that the reduced cPLA2 expression is correlated to a reduced basal AA metabolism, but is not a limiting factor for the opsonized zymosan-, PMA-, or A23187-triggered AA metabolism. We also show that in vitro ovalbumin challenge induces, only in iPM, cPLA2 activation through phosphorylation of serine residues, via a mechanism involving MAP kinases, and through increased intracellular calcium concentrations, leading to eicosanoid production. In parallel, we report that, in peritoneal macrophages, ovalbumin immunization induces the expression of CD23, the low affinity receptor for IgEs known for its involvement in allergic diseases. Thus, the modified expression of the enzymes involved in AA metabolism and the difference of response of cPM and iPM toward the antigen are important elements to understand the underlying mechanisms of ovalbumin-induced allergic responses. (+info)Prolonged exposure to lipopolysaccharide inhibits macrophage 5-lipoxygenase metabolism via induction of nitric oxide synthesis. (7/135)
LPS from bacteria can result in the development of sepsis syndrome and acute lung injury. Although acute exposure to endotoxin primes leukocytes for enhanced synthesis of leukotrienes (LT), little is known about the effect of chronic exposure. Therefore, we determined the effect of prolonged LPS treatment on 5-lipoxygenase (5-LO) metabolism of arachidonic acid in alveolar macrophages (AM) and in peripheral blood monocytes. Pretreatment of AM with LPS caused time- and dose-dependent suppression of LT synthetic capacity. LPS pretreatment failed to inhibit arachidonic acid (AA) release. The fact that LPS inhibited LT synthesis from endogenous AA more than from exogenous AA suggested an effect on 5-LO-activating protein (FLAP). In addition, an inhibitory effect of LPS treatment on AM 5-LO activity was suggested by cell-free 5-LO enzyme assay. No effect on the expression of either 5-LO or FLAP proteins was observed. New protein synthesis was necessary for LPS-induced reduction of 5-LO metabolism in AM, and immunoblotting demonstrated marked induction of NO synthase (NOS). Inhibition by LPS was reproduced by an NO donor and was abrogated by inhibitors of constitutive and inducible NOS. Compared with AM, peripheral blood monocytes exhibited no suppression by LPS of 5-LO metabolism and no induction of inducible NOS. We conclude that prolonged exposure to LPS impairs AM 5-LO metabolism by NO-mediated suppression of both 5-LO and FLAP function. Because LT contribute to antimicrobial defense, this down-regulation of 5-LO metabolism may contribute to the increased susceptibility to pneumonia in patients following sepsis. (+info)In situ amplification of 5-lipoxygenase and 5-lipoxygenase-activating protein in allergic airway inflammation and inhibition by leukotriene blockade. (8/135)
Leukotrienes are important mediators of the eosinophilic influx and mucus hypersecretion in the lungs in a murine model of asthma. We used in situ PCR in this model of human asthma to detect lung mRNA for 5-lipoxygenase (5-LO) and 5-LO-activating protein (FLAP), key proteins necessary for leukotriene synthesis. Lung tissue was obtained on day 28 from mice treated with i.p. (days 0 and 14) and intranasal (days 14, 25, 26, and 27) OVA or saline. After fixation, the tissue sections underwent protease- and RNase-free DNase digestion, before in situ RT-PCR using target-specific cDNA amplification. 5-LO and FLAP-specific mRNA was visualized by a digoxigenin detection system, and positive cells were analyzed by morphometry. 5-LO and FLAP-specific mRNA and protein were associated primarily with eosinophils and alveolar macrophages in the airways and pulmonary blood vessels in OVA-sensitized/challenged mice. 5-LO and FLAP protein expression increased on a per-cell basis in alveolar macrophages of OVA-treated mice compared with saline controls. Pulmonary blood vessel endothelial cells were also positive for 5-LO, FLAP mRNA, and protein. 5-LO inhibition significantly decreased 5-LO and FLAP-specific mRNA and protein expression in the lung inflammatory cells and endothelial cells. These studies demonstrate a marked increase in key 5-LO pathway proteins in the allergic lung inflammatory response and an important immunomodulatory effect of leukotriene blockade to decrease 5-LO and FLAP gene expression. (+info)
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5-lipoxygenase-activating protein
How FLAP activates 5-lipooxygenase is not completely understood, but there is a physical interaction between the two.[citation ... It is an integral protein within the nuclear membrane. FLAP is necessary in synthesis of leukotriene, which are lipid mediators ... Leukotrienes, which require the FLAP protein to be synthesized, have an established pathological role in allergic and ... is a protein that in humans is encoded by the ALOX5AP gene. FLAP is necessary for the activation of 5-lipoxygenase and ...
AM-679 (FLAP inhibitor)
This protein is involved in the production of cysteinyl leukotrienes which are involved in inflammation, and AM-679 has anti- ... Part 2: 3-{5-((S)-1-Acetyl-2,3-dihydro-1H-indol-2-ylmethoxy)-3-tert-butylsulfanyl-1-[4-(5-methoxy-pyrimidin-2-yl)-benzyl]-1H- ... Musiyenko, A.; Correa, L.; Stock, N.; Hutchinson, J. H.; Lorrain, D. S.; Bain, G.; Evans, J. F.; Barik, S. (2009). "A Novel 5- ... Lipoxygenase-Activating Protein Inhibitor, AM679, Reduces Inflammation in the Respiratory Syncytial Virus-Infected Mouse Eye". ...
Arachidonate 5-lipoxygenase
... and/or 271 by Mitogen-activated protein kinases, S6 kinase, protein kinase A (PKA), protein kinase C, Cdc2, and/or a Ca2+/ ... ALOX5 binds with the F actin-binding protein, coactin-like protein. Based on in vitro studies, this protein binding serves to ... This chemotactic factor stimulation concurrently causes the activation of mitogen-activated protein kinases (MAPK) which in ... Coactin-like protein (COL1), and Dicer protein A PLAT domain within its C2-like domain; this domain, by analogy to other PLAT ...
Acne
Squalene oxidation activates NF-κB (a protein complex) and consequently increases IL-1α levels. Additionally, squalene ... LTB4 promotes skin inflammation by acting on the peroxisome proliferator-activated receptor alpha (PPARα) protein. PPARα ... Once the light activates the sensitizing substance, this generates free radicals and reactive oxygen species in the skin, which ... Milk contains whey protein and hormones such as bovine IGF-1 and precursors of dihydrotestosterone. Studies suggest these ...
Leukotriene
When such cells are activated, arachidonic acid is liberated from cell membrane phospholipids by phospholipase A2, and donated ... The lipoxygenase pathway is active in leukocytes and other immunocompetent cells, including mast cells, eosinophils, ... Leukotrienes act principally on a subfamily of G protein-coupled receptors. They may also act upon peroxisome proliferator- ... activated receptors. Leukotrienes are involved in asthmatic and allergic reactions and act to sustain inflammatory reactions. ...
MK-886
"Inhibition of five lipoxygenase activating protein (FLAP) by MK-886 decreases atherosclerosis in apoE/LDLR-double knockout mice ... Jun, Joon-Il; Lau, Lester F. (July 2010). "The matricellular protein CCN1 induces fibroblast senescence and restricts fibrosis ... It may perform this by blocking the 5-lipoxygenase activating protein (FLAP), thus inhibiting 5-lipoxygenase (5-LOX), and may ...
Antileukotriene
"Inhibition of five lipoxygenase activating protein (FLAP) by MK-886 decreases atherosclerosis in apoE/LDLR-double knockout mice ... strong downregulation of CXCR3 expression on activated T cells, and downregulation of matrix metalloproteinase 9 expression ... Examples of 5-LOX inhibitors include drugs, such as meclofenamate sodium and zileuton. Some chemicals found in trace amounts in ... 188 (5): 538-544. doi:10.1164/rccm.201301-0023PP. PMID 23822826. Singh, Rakesh Kumar; Tandon, Ruchi; Dastidar, Sunanda Ghosh; ...
Essential fatty acid interactions
Other lipoxygenases-8-LO, 12-LO and 15-LO-make other eicosanoid-like products. To act, 5-LO uses the nuclear-membrane enzyme 5- ... lipoxygenase-activating protein (FLAP), first to a hydroperoxyeicosatetraenoic acid (HPETE), then to the first leukotriene, LTA ... Lipoxygenase oxidation removes no C=C double bonds and leads to the LK. After oxidation, the eicosanoids are further modified, ... They activate phospholipids to release AA from neuron cell membranes as a free fatty acid.[citation needed] During its short ...
Leukotriene C4 synthase
"Protein-protein interaction affinity chromatography of leukotriene C4 synthase". Protein Expr. Purif. 6 (3): 352-6. doi:10.1006 ... This protein is remotely related to microsomal glutathione S-transferase. The MAPEG (Membrane-Associated Proteins in Eicosanoid ... 2000). "Membrane-associated proteins in eicosanoid and glutathione metabolism (MAPEG). A widespread protein superfamily". Am. J ... The protein encoded by this gene, LTC4S (or glutathione S-transferase II) is an enzyme that converts leukotriene A4 and ...
Kári Stefánsson
The protein biology approach to this research involved trying to map complex processes using limited samples, mainly of brain ... Genes encode proteins, so identifying the genes and specific genetic variations that patients tended to share more often than ... Although publishing steadily, Stefansson was frustrated by the pace of progress and often by not knowing whether the proteins ... 5, pp. 14-18, 5 October 1999. A 2009 report by genetics ethics watchdog GeneWatch, a vehement opponent of the IHD and the use ...
Leukotriene C4
All three leukotrienes then bind at different affinities to two G-protein coupled receptors: CYSLTR1 and CYSLTR2, triggering ... Haeggström, Jesper Z.; Funk, Colin D. (2011-09-22). "Lipoxygenase and Leukotriene Pathways: Biochemistry, Biology, and Roles in ... stress and chemotherapy induce LTC4 biosynthesis by transcriptionally upregulating and activating the enzyme microsomal ... 122 (5): 518-23. PMID 8228569. Spanbroek, Rainer; Grabner, Rolf; Lotzer, Katharina; Hildner, Markus; Urbach, Anja; Ruhling, ...
MGST2
2000). "Membrane-associated proteins in eicosanoid and glutathione metabolism (MAPEG). A widespread protein superfamily". Am. J ... The MAPEG (Membrane-Associated Proteins in Eicosanoid and Glutathione metabolism) family consists of six human proteins, ... This gene encodes a protein that catalyzes the conjugation of leukotriene A4 and reduced glutathione to produce leukotriene C4 ... 161 (2 Pt 2): S20-4. doi:10.1164/ajrccm.161.supplement_1.ltta-5. PMID 10673221. Hillier LD, Lennon G, Becker M, et al. (1997 ...
Flap
... a specific kind of surgical flap 5-lipoxygenase activating protein (FLAP) The phenomenon of some variable or resource ...
Leukotriene A4
The resulting 5-HPETE yields the unstable allylic epoxide substrate LTA4 which is quickly hydrolyzed by the LTA4H (Leukotriene ... 5 (200): 200ra117. doi:10.1126/scitranslmed.3006674. ISSN 1946-6234. PMC 4016764. PMID 23986401. Abu, J. I.; Konje, J. C. ( ... In this pathway, arachidonic acid is converted into 5-hydroperoxyeicosatetraenoic acid (5-HPETE) as a result of a catalytic ... 5-LO) and FLAP (5-Lipoxygenase-activating protein) in the presence of ATP and Calcium ions. ...
MAPEG family
In molecular biology the MAPEG (Membrane-Associated Proteins in Eicosanoid and Glutathione metabolism) family of proteins are a ... This article incorporates text from the public domain Pfam and InterPro: IPR001129 (Protein domains, Protein families). ... Protein Science. 8 (3): 689-92. doi:10.1110/ps.8.3.689. PMC 2144274. PMID 10091672. ... "Crystal structure of a human membrane protein involved in cysteinyl leukotriene biosynthesis". Nature. 448 (7153): 609-12. ...
DeCODE genetics
Unlike common variants, mutations causing rare diseases tend to be in the regions of genes that encode proteins, providing both ... activated a system to isolate anyone diagnosed with the virus and to trace and quarantine all of their contacts. Iceland's ... 5, no 1 February 2011, pp. 50-65 On deCODE in the context of the new genomics: Davies, Kevin, The $1,000 Genome: The Revolution ... 5 January 2017 C Brownstein, et al., "If I knew then what I know now: The need for infrastructure to enable precision medicine ...
12-Hydroxyheptadecatrienoic acid
... activate cells by releasing the Gq alpha subunit and pertussis toxin-sensitive Gi alpha subunit from Heterotrimeric G proteins ... and lipoxygenase-derived eicosanoids". Drug Metabolism and Disposition. 39 (2): 180-90. doi:10.1124/dmd.110.035121. PMC 3033693 ... but also bound and was activated by a wide range of peptides, proteins, and other agents. BLT2 may ultimately prove to have ... It activates cells through both its high affinity (Dissociation constant [Kd] of 0.5-1.5 nM) Leukotriene B4 receptor 1 (BLT1 ...
ALOX12
... cyclic adenosine monophosphate response element-binding protein phosphorylation, and p38 mitogen-activated protein kinase ... Delta12-lipoxygenase, 12Delta-lipoxygenase, and C-12 lipoxygenase. ALOX12, often termed plate platelet-type 12-lipoxygenase, is ... ALOX12 (EC 1.13.11.31), also known as arachidonate 12-lipoxygenase, 12-lipoxygenase, 12S-Lipoxygenase, 12-LOX, and 12S-LOX is a ... Tang K, Finley RL, Nie D, Honn KV (March 2000). "Identification of 12-lipoxygenase interaction with cellular proteins by yeast ...
Chromosome 10
... rho GTPase activating protein 21 ARID5B: encoding protein AT-rich interactive domain-containing protein 5B ARMH3: Armadillo ... encoding protein Transmembrane protein 26 TMEM72: encoding protein Transmembrane protein 72 TYSND1: encoding protein Trypsin ... WW domain binding protein 1-like ZNF37A: zinc finger protein 37A ZNF438: zinc finger protein 438 ZRANB1: Zinc finger ranbp2- ... plexin domain-containing protein 2 PRAP1: encoding protein Proline rich acidic protein 1 PROSER2: proline and serine rich 2 or ...
Actin-binding protein
... p21-activated Kinase) Plectin p47PHOX Parvin (actopaxin) Prefoldin p53 PASK (Proline, Alanine rich Ste20 related Kinase) ... Actin-binding proteins (also known as ABPs) are proteins that bind to actin. This may mean ability to bind actin monomers, or ... This is a list of actin-binding proteins in alphabetical order. List: 0-9 A B C D E F G H I J K L M N O P Q R S T U V W x Y Z ... Profilin p185neu Ponticulin Protein kinase C Porin P.IB Prk1p (actin regulating kinase) Radixin (the R of ERM proteins) Rapsyn ...
GRB2
Linker of activated T cells, Lymphocyte cytosolic protein 2, MAP2, MAP3K1 MAP4K1, MED28, MST1R, MUC1, Mitogen-activated protein ... "Induced direct binding of the adapter protein Nck to the GTPase-activating protein-associated protein p62 by epidermal growth ... the guanine nucleotide exchange protein Sos and a 75-kDa protein that is a substrate for T cell antigen receptor-activated ... "The protein product of the c-cbl protooncogene is the 120-kDa tyrosine-phosphorylated protein in Jurkat cells activated via the ...
Neutrophil extracellular traps
Furthermore, delivering the granule proteins into NETs may keep potentially injurious proteins like proteases from diffusing ... The result of the process then depends on which NETosis pathway is activated. Suicidal NETosis was first described in a 2007 ... The formation of NETs is regulated by the lipoxygenase pathway - during certain forms of activation (including contact with ... tubulin and various other cytoplasmatic proteins are not present in NETs. NETs disarm pathogens with antimicrobial proteins ...
5-Hydroxyeicosatetraenoic acid
... p38 mitogen-activated protein kinases, cytosolic phospholipase A2, PI3K/Akt, and protein kinase C beta and epsilon. The ... 12-Lipoxygenase (i.e. ALOX12) to metabolize 5(S)-HETE to 5(S),12(S)-diHETE. The activity of this product has not yet been fully ... HETE family stimulate cells primarily by binding and thereby activating a dedicated G protein-coupled receptor, the ... protein complex to dissociate into its Gαi and Gβγ components with Gβγ appearing to be the component responsible for activating ...
Leukotriene B4 receptor 2
BLT2 receptors, similar to BLT1 receptors, are G protein coupled receptors that, when ligand-bound, activate G proteins that ... Finally, 12-lipoxygenase is overexpressed and the mass of 12-HETE is far higher in human prostate cancer than nearby normal ... "Induction of cyclooxygenase-2 by activated Ha-ras oncogene in Rat-1 fibroblasts and the role of mitogen-activated protein ... thereby activating calcium-activated intracellular signaling molecules; it also stimulates cells to activate Extracellular ...
Epoxygenase
... metabolites many of which act on cells by binding with and thereby activating specific and well-characterized receptor proteins ... Finally, there are relatively few metabolite-forming lipoxygenases and cyclooxygenases in the first and second pathways and ... Proteins and Proteomics. 1814 (1): 210-22. doi:10.1016/j.bbapap.2010.09.009. PMID 20869469. Moran, J. H.; Weise, R; Schnellmann ... "RTX proteins: A highly diverse family secreted by a common mechanism". FEMS Microbiology Reviews. 34 (6): 1076-112. doi:10.1111 ...
Anandamide
Endocannabinoid transporters for anandamide and 2-arachidonoylglycerol include the heat shock proteins (Hsp70s) and fatty acid ... "Exercise activates the endocannabinoid system". NeuroReport. 14 (17): 2209-2211. doi:10.1097/00001756-200312020-00015. PMID ... role of vanilloid receptors and lipoxygenases". The Journal of Neuroscience. 23 (10): 4127-4133. doi:10.1523/JNEUROSCI.23-10- ... June 2009). "Molecular identification of albumin and Hsp70 as cytosolic anandamide-binding proteins". Chemistry & Biology. 16 ( ...
Arachidonic acid
AA also activates syntaxin-3 (STX-3), a protein involved in the growth and repair of neurons. Arachidonic acid is also involved ... The enzymes 15-lipoxygenase-1 (ALOX15 and 15-lipoxygenase-2 (ALOX15B catalyzes the oxidation of arachidonic acid to 15- ... It also helps protect the brain from oxidative stress by activating peroxisome proliferator-activated receptor gamma. ... Receptors that activate this pathway include: A1 receptor D2 receptor α-2 adrenergic receptor 5-HT1 receptor PLC may also be ...
Lipoxygenase
... rabbit 15-lipoxygenase and porcine leukocyte 12-lipoxygenase catalytic domain. The protein consists of a small N-terminal PLAT ... and thereby are key regulators in the formation of lipoxygenase-dependent metabolites. In addition, cells, when so activated, ... erythrocyte type 15-lipoxygenase (or 15-lipoxygenase, erythrocyte type), reticulocyte type 15-lipoxygenase (or 15-lipoxygenase ... LOX-DB - LipOXygenases DataBase Lipoxygenases iron-binding region in PROSITE PDB: 1YGE - structure of lipoxygenase-1 from ...
TRIB1
October 2004). "Human tribbles, a protein family controlling mitogen-activated protein kinase cascades". The Journal of ... Tang K, Finley RL, Nie D, Honn KV (March 2000). "Identification of 12-lipoxygenase interaction with cellular proteins by yeast ... The protein's primary structure contains a PEST region, indicative of proteins that are highly susceptible to degradation in ... Tribbles homolog 1 is a protein kinase that in humans is encoded by the TRIB1 gene. Orthologs of this protein pseudokinase ( ...
Glutamate hypothesis of schizophrenia
The lipoxygenase-5 inhibitor minocycline has been seen to be marginally effective in halting schizophrenia progression. One of ... Okada, F.; Crow, T. J.; Roberts, G. W. (1990). "G-proteins (Gi, Go) in the basal ganglia of control and schizophrenic brain". ... Similarly, toxoplasmosis infection in the CNS (positively correlated to schizophrenia) activates inflammatory cascades, also ... Guo, W.; Shi, L.; Filizola, M.; Weinstein, H.; Javitch, J. A. (2005). "Crosstalk in G protein-coupled receptors: Changes at the ...
Prostate cancer
Transport protein ZIP1 is responsible for the transport of zinc into prostate cells. One of zinc's important roles is to change ... and is activated manually by the patient through a switch implanted in the scrotum. The latter is considered the gold standard ... Ford OH, Gregory CW, Kim D, Smitherman AB, Mohler JL (November 2003). "Androgen receptor gene amplification and protein ... Loss of the retinoblastoma (RB) protein induces androgen receptor deregulation in castration-resistant prostate cancer by ...
ALOX15
One or both of these compounds stimulates cells by binding with and activating two G protein-coupled receptors, GPR31 and the ... ALOX15 (also termed arachidonate 15-lipoxygenase, 15-lipoxygenase-1, 15-LO-1, 15-LOX-1) is, like other lipoxygenases, a seminal ... 15-lipoxygenase-2, 15-LOX-2, 15-LO-2, arachidonate 15-lipoxygenase type II, arachidonate 15-lipoxygenase, second type, and ... 15-lipoxygenase-1, 15-LOX-1, 15-LO-1, human 12/15-lipoxygenase, leukocyte-type arachidonate 12-lipoxygenase, or arachidonate ...
Platelet-derived growth factor
Proto-Oncogene+Proteins+c-sis at the US National Library of Medicine Medical Subject Headings (MeSH) McKinnon RD, Matsui T, ... However, comparing the signaling pathways between them reveals that the PI3K pathway is exclusively activated by PDGF, with EGF ... "12/15-Lipoxygenase Contributes to Platelet-derived Growth Factor-induced Activation of Signal Transducer and Activator of ... Human genes encoding proteins that belong to the platelet-derived growth factor family include: PDGFA; PDGFB; PDGFC; PDGFD PGF ...
Cysteinyl leukotriene receptor 1
CysLTR1 is a G protein-coupled receptor that links to and when bound to its CysLT ligands activates the Gq alpha subunit and/or ... Haeggström JZ, Funk CD (October 2011). "Lipoxygenase and leukotriene pathways: biochemistry, biology, and roles in disease". ... Acting through these G proteins and their subunits, ligand-bound CysLTR1 activates a series of pathways that lead to cell ... appears to be activated as a consequence of activating CysLT1: blockage of P2Y12 activation either by receptor depletion or ...
Oxidative stress
Excessive oxidative-damage leads to protein degradation or aggregation. The reaction of transition metals with proteins ... One source of reactive oxygen under normal conditions in humans is the leakage of activated oxygen from mitochondria during ... Cho KJ, Seo JM, Kim JH (July 2011). "Bioactive lipoxygenase metabolites stimulation of NADPH oxidases and reactive oxygen ... The presence of such metals in biological systems in an uncomplexed form (not in a protein or other protective metal complex) ...
List of MeSH codes (D12.776)
... p120 gtpase activating protein MeSH D12.776.402.300.700.500 - ras-GRF1 MeSH D12.776.402.300.700.700 - son of sevenless proteins ... lipoxygenase MeSH D12.776.556.579.374.450.025 - arachidonate lipoxygenases MeSH D12.776.556.579.374.450.025.020 - arachidonate ... groel protein MeSH D12.776.602.500.500.100 - fusion proteins, bcr-abl MeSH D12.776.602.500.500.320 - fusion proteins, gag-onc ... oncogene protein v-maf MeSH D12.776.964.700.750.875 - oncogene proteins v-abl MeSH D12.776.964.700.750.882 - oncogene proteins ...
Interleukin 13
15-Lipoxygenase-1 (15LO1) which is an enzyme in the fatty acid metabolism and its metabolite, 15-HETE, are highly expressed in ... Interleukin 13 (IL-13) is a protein that in humans is encoded by the IL13 gene. IL-13 was first cloned in 1993 and is located ... Heterodimerization activates both the STAT6 and the IRS. STAT6 signaling is important in initiation of the allergic response. ... The JAK Janus kinase proteins on the cytoplasmic end of the receptors allows for the phosphorylation of STAT6, which then forms ...
Clostridium perfringens alpha toxin
As a result, knowledge about the function of this particular protein greatly aids understanding of myonecrosis.[citation needed ... The C terminal domain shows similarity with non-bacterial enzymes such as pancreatic lipase, soybean lipoxygenase, and ... which activates a variety of second messenger pathways. The end-result includes activation of arachidonic acid pathway and ... 136 (5): 569-574. doi:10.1093/jb/mvh161. PMID 15632295. Naylor CE, Eaton JT, Howells A, et al. (1998). "Structure of the key ...
Specialized pro-resolving mediators
Cells metabolize DHA by ALOX12, other lipoxygenase, (12/15-lipoxygenase in mice), or an unidentified pathway to a 13S,14S- ... by either activating or inhibiting cells through binding to and thereby activating or inhibiting the activation of specific ... Certain of these PUFA-cyclopentenones bind to the sulfur residues in the KEAP1 component of the KEAP1-NFE2L2 protein complex in ... PDX is formed by the metabolism of DHA by two serial lipoxygenases, probably a 15-lipoxygenase and ALOX12. 22-Hydroxy-PD1 (also ...
Colipase
Protein domains, Membrane proteins, Enzymes, Protein families, All stub articles, Enzyme stubs). ... It is secreted by the pancreas in an inactive form, procolipase, which is activated in the intestinal lumen by trypsin. Its ... the N-terminal domains of lipoxygenases and the C-terminal domain of alpha-toxin. These non-catalytic domains in the latter ... In humans, the colipase protein is encoded by the CLPS gene. Colipase is also a family of evolutionarily related proteins. ...
Cysteinyl leukotriene receptor 2
CysLTR2, similar to CysLTR1, is a G protein-coupled receptor that links to and when bound to its CysLT ligands activates the Gq ... "WikiGenes - Collaborative Publishing". Haeggström JZ, Funk CD (October 2011). "Lipoxygenase and leukotriene pathways: ... Acting through these G proteins and their subunits, ligand-bound CysLTR1 activates a series of pathways that lead to cell ... CysLTR2 encodes a protein composed of 347 amino acids and shows only modest similarity to the CysLTR1 gene in that its protein ...
TRPA1
It can be activated at sites of tissue injury or sites of inflammation directly by endogenous mediators or indirectly as a ... TRPA1+protein,+human at the US National Library of Medicine Medical Subject Headings (MeSH) (CS1 maint: DOI inactive as of July ... May 2013). "Systematic analysis of rat 12/15-lipoxygenase enzymes reveals critical role for spinal eLOX3 hepoxilin synthase ... In this animal model of pain perception, the hepoxilins are released in the spinal cord directly activate TRPA (and also TRPV1 ...
Cytostasis
"Tumor cell killing and cytostasis by C3H/HeJ macrophages activated in vitro by lipid A-associated protein and interferon gamma ... Study shows that metabolites of the lipoxygenase pathway are involved with the antiproliferation induce by PUFA. However, PUFA ... Nitric oxide - activated macrophages produce large amounts of nitric oxide (NO), which induces both cytostasis and cytotoxicity ... Lipopolysaccharide (LPS) and lipid A-associated protein - studies have demonstrated that LPS and LAP are potent macrophage ...
Aspirin
In 2012, salicylic acid was found to activate AMP-activated protein kinase, which has been suggested as a possible explanation ... It is proposed that this aspirin-triggered transition of COX-2 from cyclooxygenase to lipoxygenase activity and the ... May 2012). "The ancient drug salicylate directly activates AMP-activated protein kinase". Science. 336 (6083): 918-22. Bibcode: ... Acetylation of cellular proteins is a well-established phenomenon in the regulation of protein function at the post- ...
Myricetin
... suppressed the release of IL-2 protein from mouse EL-4 T cells that had been stimulated with phorbol 12-myristate 13- ... Myricetin, along with other lipoxygenase- and cyclooxygenase-blocker flavonoids are seen to have significant anti-inflammatory ... collagen and platelet activating factor (PAF). It inhibited specific receptor binding of PAF in rabbit platelets. The compound ... and proteins. Gradual but steady accretion of such damage can lead to the development of many diseases and conditions including ...
13-Hydroxyoctadecadienoic acid
Kelavkar, U. P; Cohen, C (2004). "15-lipoxygenase-1 expression upregulates and activates insulin-like growth factor-1 receptor ... HODE directly activate human (but not mouse) GPR132 (G protein coupled receptor 132, also termed G2A) in Chinese hamster ovary ... 12-lipoxygenase, and 15-lipoxygenase-2, and selected metabolites of the latter lipoxygenases show no such association. ... 13-HODE, 13-oxoODE, and 13-EE-HODE (along with their 9-HODE counterparts) directly activate peroxisome proliferator-activated ...
RAR-related orphan receptor alpha
The protein encoded by this gene is a member of the NR1 subfamily of nuclear hormone receptors. In humans, 4 isoforms of RORα ... RORα, which activates transcription of Bmal1, and REV-ERBα, which represses transcription of Bmal1, compete to bind to the RRE ... The protein structure of RORα consists of four canonical functional groups: an N-terminal (A/B) domain, a DNA-binding domain ... ATXN1: ATXN1 and RORα form part of a protein complex in Purkinje cells. FOXP3: FOXP3 directly represses the transcriptional ...
Mutagen
Polycyclic aromatic hydrocarbons (PAH), when activated to diol-epoxides can bind to DNA and form adducts. Alkylating agents ... a natural product of cellular cyclooxygenases and lipoxygenases, breaks down to form 4-hydroxy-2(E)-nonenal, 4-hydroperoxy-2(E ... effects as they do not result in residue changes that have significant effect on the structure and function of the proteins. ... 7 Suppl 5 (suppl. 5): 1-248. doi:10.1002/em.2860070902. PMID 3905369. Benigni R, Bossa C (May 2011). "Alternative strategies ...
Lipoxin
The two LXBs also trigger activation of Suppressor of cytokine signaling proteins (see SOCS proteins) which, in turn, inhibit ... Wu L, Li HH, Wu Q, Miao S, Liu ZJ, Wu P, Ye DY (2015). "Lipoxin A4 Activates Nrf2 Pathway and Ameliorates Cell Damage in ... The double oxygenations may be conducted within a single cell type which possess ALOX5 and an enzyme with 15-lipoxygenase ... FPR2, which is now termed the ALX, ALX/FPR, or ALX/FPR2 receptor, is a G protein coupled receptor initially identified as a ...
Cytochrome P450 omega hydroxylase
Cell biology, Metabolic pathways, Fatty acids, EC 1.14, Cytochrome P450, Integral membrane proteins). ... 20-hydroxy EPA and 20-hydroxy-DHA do stimulate Peroxisome proliferator-activated receptor alpha but their range of biological ... "Metabolism of arachidonic acid by canine polymorphonuclear leukocytes synthesis of lipoxygenase and omega-oxidized metabolites ... 5) CYP4F22 ω-hydroxylates extremely long very long chain fatty acids, i.e. fatty acids that are 28 or more carbons long. The ω- ...
Genetic and Inflammatory Mechanisms in Stroke: Factors in Atherosclerosis and Stroke, Atherogenesis: An Inflammatory Process,...
In response to the presence of certain activating substances, including oxidized LDL, monocyte chemoattractant protein 1 (MCP-1 ... High-sensitivity C-reactive protein (hsCRP) and stroke risk. Acute phase proteins, hsCRP in particular, have been the most ... Platelets also can be activated by platelet-activating factor (PAF), which is produced by monocytes, endothelial cells, and ... C-reactive protein levels and outcomes after statin therapy. N Engl J Med. 2005 Jan 6. 352(1):20-8. [QxMD MEDLINE Link]. ...
Science Clips - Volume 12, Issue 23, July 14, 2020
... protein (ALOX5AP), whereas M2 macrophages had a high level expression of arachidonate 15-lipoxygenase (ALOX15). Polarization of ... Elevated levels of C-reactive protein, d-dimer, and troponin were found in 100%, 91%, and 71% of the patients, respectively; 62 ... other structural and nonstructural VZV proteins in both BM and blood (peripheral blood mononuclear cells [PBMCs]). The ... The 5-, 10-, and 25-year probabilities that the ICERs are below US$50 k (US$100 k)/QALY are 6% (15%), 59% (82%) and 96% (100 ...
Coronary Artery Disease Pipeline Insight | Coronary Artery Disease Companies and Therapies
Genetic Landscapes and Prognostic Implications of Circadian rhythm in Non-small Cell Lung Cancer | Research Square
Ral GTPase Activating Protein Catalytic Subunit Alpha 2. 0.209187368. 1.232676. 0.963034. 1.577816 ... 11A-B). Furthermore, there were significantly increased levels of infiltrates of activated memory CD4+ T cells, T follicular ... 11C-D). Meanwhile, there were significantly increased levels of infiltrates of plasma cells, activated memory CD4+ T cells, ... PROTEIN_RESPONSE, MYC_TARGETS_V1, G2M_CHECKPOINT, and DNA_REPAIR in the low-risk group (Fig. 4). It indicated the differential ...
NIOSHTIC-2 Search Results - Full View
MESH TREE NUMBER CHANGES - 2012 MeSH. August 19, 2011
N6.230.132.644.875 Wnt Proteins D12.644.276.984 Wnt1 Protein D12.644.276.984.500 D12.776.467.984.100 D12.776.467.984.500 ... E2.792.833.230 Blood Protein Electrophoresis E1.450.150.100.110 E1.370.225.124.100.110 E5.200.124.100.110 Blood Safety E1.450. ... A1.923.47.412 Insect Proteins D12.776.466 D12.776.92.500 Instillation, Drug E2.319.267.641 Insulin D6.472.699.587.740.625 ... E5.200.812.735.50.450 LDL-Receptor Related Protein 1 D23.50.301.264.35.502 D23.101.100.110.498 (Replaced for 2012 by Low ...
SULFASALAZINE
2-HYDROXY-5-((4-((2-PYRIDINYLAMINO)SULFONYL)PHENYL)AZO)BENZOIC ACID [WHO-IP] Source:. ... InChI=1S/C18H14N4O5S/c23-16-9-6-13(11-15(16)18(24)25)21-20-12-4-7-14(8-5-12)28(26,27)22-17-3-1-2-10-19-17/h1-11,23H,(H,19,22)(H ... Inhibition of arachidonate 5-lipoxygenase by sulfasalazine and its major metabolites was observed at higher concentrations (2-3 ... BENZOIC ACID, 2-HYDROXY-5-(2-(4-((2-PYRIDINYLAMINO)SULFONYL)PHENYL)DIAZENYL)- Source:. ...
Browse by Course Code - Epsilon Archive for Student Projects
In the Field: News
DeCS
2011; 5-LIPOOXYGENASE-ACTIVATING PROTEINS was indexed under CARRIER PROTEINS and MEMBRANE PROTEINS 1990-2010. ... 5 LO Activating Protein 5 Lipoxygenase Activating Protein 5 Lipoxygenase Activating Proteins 5-LO-Activating Protein 5- ... Lipoxygenase-Activating Protein Arachidonate 5 Lipoxygenase Activating Protein Arachidonate 5 Lipoxygenase Activating Proteins ... 5 LO Activating Protein. 5 Lipoxygenase Activating Protein. 5 Lipoxygenase Activating Proteins. 5-LO-Activating Protein. 5- ...
Nordihydroguaiaretic acid protects hippocampal neurons against amyloid β-peptide toxicity, and attenuates free radical and...
Another lipoxygenase inhibitor (AA861) also protected against Aβ and iron toxicity whereas the the 5-lipoxygenase-activating ... protein inhibitor L655,238 and the cyclooxygenase inhibitor indomethacin were ineffective. These findings suggest that NDGA can ... Another lipoxygenase inhibitor (AA861) also protected against Aβ and iron toxicity whereas the the 5-lipoxygenase-activating ... Another lipoxygenase inhibitor (AA861) also protected against Aβ and iron toxicity whereas the the 5-lipoxygenase-activating ...
Glucocorticoids stimulate inflammatory 5-lipoxygenase gene expression and protein translocation in the brain
... Academic Article ... In human monocytes, 5-LO mRNA content increases on exposure to the synthetic glucocorticoid dexamethasone, which prompted us to ... We found increased levels of 5-LO mRNA and protein in hippocampus and cerebellum of glucocorticoid-treated rats; 5-LO- ... activating protein (FLAP) mRNA content was not affected. Using western immunoblotting, we also observed the concurrent ...
Pesquisa | Portal Regional da BVS
5. Relationship between Arachidonate 5-Lipoxygenase-Activating Protein Gene and Peripheral Arterial Disease in Elderly Patients ... Arachidonate 5-lipoxygenase-activating protein (ALOX5AP) plays an important role in atherosclerosis pathogenesis. In this study ... METHODS: PubMed and Embase were searched for peer-reviewed publications between 1 January 2001 and 5 May 2022 using the terms ... Risk of bias was assessed using ROBINS-I. RESULTS: Of the 7048 articles screened, 5 observational studies with 119,123 patients ...
Status - The Globin Gene Server - Leiden Open Variation Database
mitogen-activated protein kinase kinase kinase 7. 2. 2. 2. MYB. Homo sapiens v-myb myeloblastosis viral oncogene homolog. 12. ... endothelial PAS domain protein 1. 1. 1. 1. ERCC2. excision repair cross-complementing rodent repair deficiency, complementati. ... mitogen-activated protein kinase kinase kinase 5. 2. 2. 2. MAP3K7. ...
Tissue expression of ALOX5AP - Summary - The Human Protein Atlas
GO:0019372 [lipoxygenase pathway]. GO:0031965 [nuclear membrane]. GO:0043085 [positive regulation of catalytic activity]. GO: ... Protein evidence (Ezkurdia et al 2014). Protein evidence (Kim et al 2014). RAS pathway related proteins. Ribosomal proteins. ... The protein classes assigned to this protein are shown if expanding the data in the protein class column. Parent protein ... 3TM proteins predicted by MDM. Disease related genes. Protein evidence (Kim et al 2014). Protein evidence (Ezkurdia et al 2014) ...
HuGE Navigator|HuGE Literature Finder|PHGKB
Human lipoxygenase pathway gene variation and association with markers of subclinical atherosclerosis in the diabetes heart ... Assessment of association between lipoxygenase genes variants in elderly Greek population and type 2 diabetes mellitus. ... The gene encoding 5-lipoxygenase activating protein confers risk of myocardial infarction and stroke. Nature genetics 2004 Mar ... The arachidonate 5-lipoxygenase activating protein gene polymorphism is associated with the risk of scleroderma-related ...
Lipoxygenase inhibitors inhibit growth of human pancreatic cancer xenografts and induce apoptosis
Lipoxygenase inhibitors attenuate growth of human pancreatic cancer xenografts and induce apoptosis through the... ... proteins Bcl-2 and Mcl-1 was significantly decreased after LOX inhibitor treatment while that of the. proapoptotic protein bax ... 8 were activated after treatment, concomitant with cleavage of the capase-3 substrate poly(ADP-. ribose) polymerase. In vivo ... Lipoxygenase inhibitors attenuate growth of human pancreatic cancer xenografts and induce apoptosis. through the mitochondrial ...
Programme
Macrocyclic Modalities for Modulation of Protein-Protein Interactions (OC06). Dr St phanie GUERET ASTRAZENECA MPI SATELLITE ... Dr Erik Hett received his Ph.D. from Harvard University in the lab of Dr Eric Rubin, studying protein-protein interactions ... A Chemical Approach to Map Protein Interactions at the Cell Surface (T12) ... led major projects of the satellite unit focusing on the synthesis development of mixed macrocycles to modulate protein-protein ...
Angela Schmider | Harvard Catalyst Profiles | Harvard Catalyst
... is necessary for thrombin-induced NF-kappaB activation in endothelial cells through AMP-activated protein kinase and protein ... Paria BC, Bair AM, Xue J, Yu Y, Malik AB, Tiruppathi C. Ca2+ influx induced by protease-activated receptor-1 activates a feed- ... Thioredoxin Interacting Protein Is Required for a Chronic Energy-Rich Diet to Promote Intestinal Fructose Absorption. iScience ... Diabetes regulates fructose absorption through thioredoxin-interacting protein. Elife. 2016 10 11; 5. PMID: 27725089. ...
Search: ce enriched:breast;macrophages;Very high,High,Moderate - The Human Protein Atlas
Protein classi Protein class(es) of the gene product according to selected gene lists. List of protein classes. ... Protein classi Protein class(es) of the gene product according to selected gene lists. List of protein classes. ... Cell Cycle Dependent Proteini Cell cycle dependency of protein expression in the FUCCI U-2 OS cell line, determined by ICC-IF ... Cell Cycle Dependent Proteini Cell cycle dependency of protein expression in the FUCCI U-2 OS cell line, determined by ICC-IF ...
Synthesis of N-heterocycles as anti-asthma drugs and compounds with antimycobacterial properties
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UCL...
Muskelbivirkninger av statiner - hva vet vi om mekanismer og hvordan diagnostiseres de? - Farmatid
Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. New England Journal of Medicine 2008 ... The SLCO1B1*5 genetic variant is associated with statin-induced side effects. J Am Coll Cardiol 2009; 54(17): 1609-16. ... Drug Metab Dispos 2002; 30(5): 505-12.. *Prueksaritanont T, Ma B, Fang X et al. beta-oxidation of simvastatin in mouse liver ... The prevalence of statin induced myotoxicity is between 1-5 %, but serious adverse effects are rare. The primary aim of this ...
ANTI-INFLAMMATORY HERBAL LIPOSOMAL PROPARATIONS FOR HEALTHY AGING - AGINGSCIENCES™ - Anti-Aging Firewalls™
... strong promotion of the NRF2 protein which activates hundreds of anti-inflammatory and "anti-oxidant response genes like heme ... and lipoxygenase (COX). INOs, LOX, and COX are key enzymes that mediate inflammatory(ref)" Further, curcumin inhibits the ... Gingerols, found in ginger (Zingiber officinale Roscoe, Zingiberaceae). Gingerols can activate autophagy(ref), "The findings of ... We measured interleukin-1 receptor antagonist (IL-1ra), interleukin (IL)-6, -10, C-reactive protein (CRP), and tumor necrosis ...
MESH TREE NUMBER CHANGES - 2012 MeSH. August 19, 2011
N6.230.132.644.875 Wnt Proteins D12.644.276.984 Wnt1 Protein D12.644.276.984.500 D12.776.467.984.100 D12.776.467.984.500 ... E2.792.833.230 Blood Protein Electrophoresis E1.450.150.100.110 E1.370.225.124.100.110 E5.200.124.100.110 Blood Safety E1.450. ... A1.923.47.412 Insect Proteins D12.776.466 D12.776.92.500 Instillation, Drug E2.319.267.641 Insulin D6.472.699.587.740.625 ... E5.200.812.735.50.450 LDL-Receptor Related Protein 1 D23.50.301.264.35.502 D23.101.100.110.498 (Replaced for 2012 by Low ...
MESH TREE NUMBER CHANGES - 2012 MeSH. August 19, 2011
N6.230.132.644.875 Wnt Proteins D12.644.276.984 Wnt1 Protein D12.644.276.984.500 D12.776.467.984.100 D12.776.467.984.500 ... E2.792.833.230 Blood Protein Electrophoresis E1.450.150.100.110 E1.370.225.124.100.110 E5.200.124.100.110 Blood Safety E1.450. ... A1.923.47.412 Insect Proteins D12.776.466 D12.776.92.500 Instillation, Drug E2.319.267.641 Insulin D6.472.699.587.740.625 ... E5.200.812.735.50.450 LDL-Receptor Related Protein 1 D23.50.301.264.35.502 D23.101.100.110.498 (Replaced for 2012 by Low ...
MESH TREE NUMBER CHANGES - 2012 MeSH. August 19, 2011
N6.230.132.644.875 Wnt Proteins D12.644.276.984 Wnt1 Protein D12.644.276.984.500 D12.776.467.984.100 D12.776.467.984.500 ... E2.792.833.230 Blood Protein Electrophoresis E1.450.150.100.110 E1.370.225.124.100.110 E5.200.124.100.110 Blood Safety E1.450. ... A1.923.47.412 Insect Proteins D12.776.466 D12.776.92.500 Instillation, Drug E2.319.267.641 Insulin D6.472.699.587.740.625 ... E5.200.812.735.50.450 LDL-Receptor Related Protein 1 D23.50.301.264.35.502 D23.101.100.110.498 (Replaced for 2012 by Low ...
MESH TREE NUMBER CHANGES - 2012 MeSH. August 19, 2011
N6.230.132.644.875 Wnt Proteins D12.644.276.984 Wnt1 Protein D12.644.276.984.500 D12.776.467.984.100 D12.776.467.984.500 ... E2.792.833.230 Blood Protein Electrophoresis E1.450.150.100.110 E1.370.225.124.100.110 E5.200.124.100.110 Blood Safety E1.450. ... A1.923.47.412 Insect Proteins D12.776.466 D12.776.92.500 Instillation, Drug E2.319.267.641 Insulin D6.472.699.587.740.625 ... E5.200.812.735.50.450 LDL-Receptor Related Protein 1 D23.50.301.264.35.502 D23.101.100.110.498 (Replaced for 2012 by Low ...
MESH TREE NUMBER CHANGES - 2012 MeSH. August 19, 2011
N6.230.132.644.875 Wnt Proteins D12.644.276.984 Wnt1 Protein D12.644.276.984.500 D12.776.467.984.100 D12.776.467.984.500 ... E2.792.833.230 Blood Protein Electrophoresis E1.450.150.100.110 E1.370.225.124.100.110 E5.200.124.100.110 Blood Safety E1.450. ... A1.923.47.412 Insect Proteins D12.776.466 D12.776.92.500 Instillation, Drug E2.319.267.641 Insulin D6.472.699.587.740.625 ... E5.200.812.735.50.450 LDL-Receptor Related Protein 1 D23.50.301.264.35.502 D23.101.100.110.498 (Replaced for 2012 by Low ...
MESH TREE NUMBER CHANGES - 2012 MeSH. August 19, 2011
N6.230.132.644.875 Wnt Proteins D12.644.276.984 Wnt1 Protein D12.644.276.984.500 D12.776.467.984.100 D12.776.467.984.500 ... E2.792.833.230 Blood Protein Electrophoresis E1.450.150.100.110 E1.370.225.124.100.110 E5.200.124.100.110 Blood Safety E1.450. ... A1.923.47.412 Insect Proteins D12.776.466 D12.776.92.500 Instillation, Drug E2.319.267.641 Insulin D6.472.699.587.740.625 ... E5.200.812.735.50.450 LDL-Receptor Related Protein 1 D23.50.301.264.35.502 D23.101.100.110.498 (Replaced for 2012 by Low ...
MESH TREE NUMBER CHANGES - 2012 MeSH. August 19, 2011
N6.230.132.644.875 Wnt Proteins D12.644.276.984 Wnt1 Protein D12.644.276.984.500 D12.776.467.984.100 D12.776.467.984.500 ... E2.792.833.230 Blood Protein Electrophoresis E1.450.150.100.110 E1.370.225.124.100.110 E5.200.124.100.110 Blood Safety E1.450. ... A1.923.47.412 Insect Proteins D12.776.466 D12.776.92.500 Instillation, Drug E2.319.267.641 Insulin D6.472.699.587.740.625 ... E5.200.812.735.50.450 LDL-Receptor Related Protein 1 D23.50.301.264.35.502 D23.101.100.110.498 (Replaced for 2012 by Low ...
Arachidonate 5-lipoxygenase activInhibitorsALOX5APFLAPArachidonic acidLeukotrienesPathwayPolymorphismEnzymeCyclooxygenaseInhibitor2017Signaling Adaptor ProteinsInhibitPlatelet-derivePathwaysInflammationEnzymesAmino AcidsInhibitsMacrophagesAnti-inflammatoryAtherosclerosisReceptorsPhospholipaseGTPaseGenesTissueIC50AdaptorMRNAPhosphorylationMoleculesCytokinesInducesMembraneKinaseGene expressionLipidSynthaseLocalizationNucleotideTransmembrane proteinSynapticExpressionMitochondrialAdverse effectsExcessiveNeurons
Arachidonate 5-lipoxygenase activ4
- M1 macrophages exhibited preferential induction of arachidonate 5-lipoxygenase activating protein (ALOX5AP), whereas M2 macrophages had a high level expression of arachidonate 15-lipoxygenase (ALOX15). (cdc.gov)
- Arachidonate 5-lipoxygenase-activating protein (ALOX5AP) plays an important role in atherosclerosis pathogenesis. (bvsalud.org)
- The arachidonate 5-lipoxygenase activating protein gene polymorphism is associated with the risk of scleroderma-related interstitial lung disease: a multicentre European Scleroderma Trials and Research group (EUSTAR) study. (cdc.gov)
- Arachidonate 5-lipoxygenase-activating protein (ALOX5AP) gene and coronary heart disease risk in familial hypercholesterolemia. (cdc.gov)
Inhibitors5
- Amira Pharmaceuticals (San Diego, CA) and GlaxoSmithKline (Middlesex, United Kingdom) have agreed to develop, manufacture and commercialize 'FLAP' (5-lipoxygenase activating protein) inhibitors for the treatment of respiratory and cardiovascular disease. (pharmtech.com)
- Apoptosis of pancreatic cancer cells induced by LOX inhibitors (including the nonselective LOX inhibitor nordihydroguaiaretic acid, the 5-LOX inhibitor Rev-5901, and the 12-LOX inhibitor baicalein) was confirmed by growth inhibition, annexin V binding, and terminal deoxynucleotidyl transferase-mediated nick end labeling assay in MiaPaCa-2 and AsPC-1 human pancreatic cancer cells. (cyclingforums.com)
- However, the currently available "5-LOX inhibitors" are not safe enough to be taken without medical supervision. (our-arthritis.com)
- However, 5 RCTs of 3 structurally distinct inhibitors also indicate that such compounds elevate the risk of myocardial infarction and stroke. (jci.org)
- NSAIDs, which include both traditional NSAIDs (tNSAIDs) and selective inhibitors of COX-2 and which are among the most commonly used drugs ( 5 ), relieve pain and inflammation by suppressing the COX function of PGHS and the consequent formation of PGE 2 ( 6 ) and prostacyclin (PGI 2 ) ( 7 ), but perhaps also of other prostanoids. (jci.org)
ALOX5AP1
- 5-Lipoxygenase activating protein (ALOX5AP) gene variants associate with the presence of xanthomas in familial hypercholesterolemia. (cdc.gov)
FLAP3
- Insertion of transmembrane 5-lipoxygenase activating protein (FLAP) into nanodiscs towards structure function studies of complex formation with soluble proteins. (slu.se)
- 5-LO-activating protein (FLAP) mRNA content was not affected. (uab.edu)
- An attractive novel dual target strategy was the inhibition of the 5-lipoxygenase activating protein (FLAP) and antagonism of the prostaglandin D2 receptor CRTh2. (ucl.ac.uk)
Arachidonic acid10
- Our previous studies have demonstrated that blockade of either the 5-lipoxygenase (LOX) or 12-LOX pathway of arachidonic acid metabolism inhibited pancreatic cancer cell proliferation and induced apoptosis. (cyclingforums.com)
- In order to neutralise arachidonic acid, increased amounts of 5-lipoxygenase (5-LOX) are produced in our system. (our-arthritis.com)
- Increased 5-LOX enzyme values and end products of arachidonic acid breakdown are closely connected with middle and old age diseases. (our-arthritis.com)
- The diagram below clearly shows how typical Western diet food causes a surplus of arachidonic acid to be created, resulting in harmful consequences of increased 5-lipoxygenase values. (our-arthritis.com)
- To control the severity and duration of acute inflammation, cells expressing 5-lipoxygenase (5-LOX) and 12/15-lipoxygenase (12/15-LOX) oxygenate arachidonic acid in tandem to synthesize LXA 4 locally. (elifesciences.org)
- U73122 significantly inhibits aggregation of human platelets induced by a variety of agonists, including collagen, thrombin, ADP, arachidonic acid, with IC50 of 1-5 μM. (selleckchem.com)
- [5] It is degraded primarily by the fatty acid amide hydrolase (FAAH) enzyme, which converts anandamide into ethanolamine and arachidonic acid. (wikipedia.org)
- Cysteinyl leukotrienes (CysLTs) are potent lipid inflammatory mediators synthesized from arachidonic acid, through the 5-lipoxygenase (5-LO) pathway. (web.app)
- Arachidonic acid is acted upon by the enzyme 5-lipoxygenase to synthesize LTB4and cysteinyl leukotrienes (cys-LT C4, D4, and E4). (web.app)
- Inhibitory effect of curcumin, a food spice from turmeric, on platelet-activating factor- and arachidonic acid-mediated platelet aggregation through inhibition of thromboxane formation and Ca2+ signaling. (semanticscholar.org)
Leukotrienes5
- In the brain, the expression of 5-lipoxygenase (5-LO), the enzyme responsible for the synthesis of inflammatory leukotrienes, increases during aging. (uab.edu)
- 5-lipoxygenase stimulates the production of pro-inflammatory molecules in the body called leukotrienes. (our-arthritis.com)
- The 3-acetyl-11-keto-beta-boswellic acid (AKBA) has turned out to be the most effective in inhibiting 5-lipoxygenase and preventing the creation of pro-inflammatory leukotrienes. (our-arthritis.com)
- The cysteinyl leukotrienes (cys-LTs) are 5-lipoxygenase pathway products implicated in asthma, in particular, by their function as smooth muscle constrictors of airways and microvasculature. (web.app)
- 5-lipoxygenase ( 5-LO ) generates the leukotrienes. (chemeurope.com)
Pathway3
- Thus, glucocorticoid-mediated up-regulation of the neuronal 5-LO pathway may contribute to rendering an aging brain vulnerable to degeneration. (uab.edu)
- Human lipoxygenase pathway gene variation and association with markers of subclinical atherosclerosis in the diabetes heart study. (cdc.gov)
- On the other hand, inhibition from the COX pathway by NSAIDs may shunt the rate of metabolism of arachidonic acidity into the additional path, i.e., activating the lipoxygenase (5-LOX) pathway. (cancerhugs.com)
Polymorphism1
- Corrigendum to 'Arachidonate 5-Lipoxygenase (ALOX5) gene polymorphism is associated with Alzheimer's disease and body mass index [Šerý et al. (archives-ouvertes.fr)
Enzyme2
- Heart diseases, carcinoma, chronic pulmonary diseases, Alzheimer's disease, pneumonia and influenza are all linked with this enzyme that is produced by our body.1 This enzyme is called 5-lipoxygenase or 5-LOX for short, which, when generated by the body in excessive amounts, gives rise to a whole cascade of dangerous inflammatory reactions. (our-arthritis.com)
- 2-5 Scientists have been familiar with this enzyme for some time due to its role in occurrence of arthritis, asthma and Crohn's disease, which is why the pharmaceutical industry aims to develop a safe drug to alleviate the effect of 5-lipoxygenase. (our-arthritis.com)
Cyclooxygenase2
- Another lipoxygenase inhibitor (AA861) also protected against Aβ and iron toxicity whereas the the 5-lipoxygenase-activating protein inhibitor L655,238 and the cyclooxygenase inhibitor indomethacin were ineffective. (elsevier.com)
- Curcumin is a cell-permeable, antioxidant that acts as a dual inhibitor of 5-lipoxygenase (IC= 8 M) and cyclooxygenase (IC= 52 M). (agscientific.com)
Inhibitor5
- In the present study, the lipoxygenase inhibitor/antioxidant nordihydroguaiaretic acid (NDGA) protected cultured rat hippocampal neurons against the toxicity of Aβ in a concentration-dependent manner. (elsevier.com)
- Expression of the antiapoptotic proteins Bcl-2 and Mcl-1 was significantly decreased after LOX inhibitor treatment while that of the proapoptotic protein bax was increased. (cyclingforums.com)
- Also shown to be a p300/CREB-binding protein-specific inhibitor of histone acetyltransferase, inhibiting the acetylation of histones H3 and H4 with an ICof ~25 M. Does not affect p300/CREB binding protein-associated factor (PCAF). (agscientific.com)
- CHIR-99021 is a GSK-3α/β inhibitor with an IC50 of 10 and 6.7 nM,showing 500-fold selectivity over its closest homologs CDC2 and ERK2, as well as other protein kinases. (dcchemicals.com)
- BIO (6-bromoindirubin-3'-oxime) is a specific inhibitor of GSK-3 with IC50 of 5 nM for GSK-3α/β, shows >16-fold selectivity over CDK5, also a pan-JAKinhibitor. (dcchemicals.com)
20171
- Rheumatology (Oxford, England) 2017 05 56 (5): 844-852. (cdc.gov)
Signaling Adaptor Proteins4
- CARD Signaling Adaptor Proteins" is a descriptor in the National Library of Medicine's controlled vocabulary thesaurus, MeSH (Medical Subject Headings) . (uams.edu)
- A family of intracellular signaling adaptor proteins that contain caspase activation and recruitment domains. (uams.edu)
- This graph shows the total number of publications written about "CARD Signaling Adaptor Proteins" by people in UAMS Profiles by year, and whether "CARD Signaling Adaptor Proteins" was a major or minor topic of these publications. (uams.edu)
- Below are the most recent publications written about "CARD Signaling Adaptor Proteins" by people in Profiles over the past ten years. (uams.edu)
Inhibit3
- This system continues to be disputed because particular NSAIDs that trigger enteropathy usually do not just inhibit COX but also regulate 5-LOX. (cancerhugs.com)
- More recent proof has provided obvious proof that diclofenac will not inhibit 5-LOX in rats (Maier relevance is definitely hard to assess. (cancerhugs.com)
- Spice phenolics inhibit human PMNL 5-lipoxygenase. (semanticscholar.org)
Platelet-derive1
- In response to the presence of certain activating substances, including oxidized LDL, monocyte chemoattractant protein 1 (MCP-1), interleukin (IL)-8, and platelet-derived growth factor (PDGF), leukocytes migrate into the wall of the artery (see the image below). (medscape.com)
Pathways1
- The classical pathways add molecular oxygen (O 2 ) via lipoxygenase or COX . (chemeurope.com)
Inflammation5
- Activated retina-specific T cells then traffic to the eye and elicit inflammation that starts 9-11 days and peaks 14-16 days after immunization ( Caspi, 2010 ). (elifesciences.org)
- These results suggest that CS may aggravate lung inflammation by activating EOS which, in turn, release inflammatory mediators promoting inflammatory cell recruitment and lung remodeling. (ispub.com)
- Eosinophils are particularly evident in chronic lung inflammation where their products appear to play roles both in bronchial hyper-responsiveness and in tissue remodeling, leading to compromised lung function [ 5 , 6 ]. (ispub.com)
- Additionally, eosinophil cytoplasmic lipid bodies contain cyclooxygenases (COX), lipoxygenases, and phospholipase A2, all of which contribute to inflammation through their role in synthesis of proinflammatory eicosanoids [ 18 ]. (ispub.com)
- By inhibiting COXs and lipoxygenases (LOXs), marine omega-3s can reduce inflammation caused by the metabolism of AA. (bmj.com)
Enzymes4
- Members of this family of proteins are often found associated with histone-modifying enzymes and protein complexes that regulate gene expression. (musc.edu)
- commonly known as COX) enzymes, lipoxygenases, and epoxygenases to form a mesmerizing array of biologically active products. (jci.org)
- The COX enzymes are bisfunctional proteins, possessing both COX and hydroperoxidase (HOX) activities, catalyzing the biotransformation of AA into the PG endoperoxide intermediates PGG 2 and PGH 2 . (jci.org)
- With following highly we are - N-acetylneuraminic enzymes, proteins, alpha and surface, dyslexia, and Digestion - building autoreactivity suggests primarily we are. (erik-mill.de)
Amino Acids2
- GLU and its biochemical "cousin," aspartic acid or aspartate (ASP), are the two most plentiful amino acids in the brain (5). (antiaging-nutrition.com)
- GLU and ASP can be synthesized by cells from each other, and GLU can be made from various other amino acids, as well (5). (antiaging-nutrition.com)
Inhibits5
- Curcumin also inhibits glutathione S-transferase,induction of nitric oxide in activated macrophages and inhibits EGF-induced tyrosine phosphorylation of EGF receptors. (agscientific.com)
- U73122 potently inhibits human 5-lipoxygenase (5-LO) . (selleckchem.com)
- U-73122 (10 μM) inhibits the production of IP3 and the subsequent rapid increase in cytosolic Ca 2+ induced by either thrombin or U-46619 through inhibiting hydrolysis of phosphatidyl[ 3 H]inositol and phosphatldyl[ 3 H]inosito1 4,5-bisphosphate catalyzed by a soluble fraction from platelets (K i =9 and 40 μM, respectively). (selleckchem.com)
- This increase in cyclic AMP activates protein kinase A, which in turn inhibits myosin phosphorylation and lowers intracellular ionic calcium concentration, resulting in muscle relaxation. (medscape.com)
- CHIR 99021 is a small organic molecule that inhibits GSK3α and GSK3β by competing for their ATP-binding sites.In vitro kinase assays reveal that CHIR 99021 specifically inhibits GSK3β (IC50=~5 nM) and GSK3α (IC50=~10 nM), with little effect on other kinases[2]. (dcchemicals.com)
Macrophages2
- These macrophages, in addition to smooth muscle cells, activate T cells by presenting antigens, including oxidized LDL. (medscape.com)
- Other trophic factors, such as IL-2, TNF-α, and granulocyte-macrophage stimulating factor, cause activated T cells to produce interferon-γ, TNF-α, and TNF-β, leading to stimulation of macrophages and further up-regulation of leukocyte adhesion molecules. (medscape.com)
Anti-inflammatory1
- Since these diseases are being increasingly eliminated, the anti-inflammatory reaction of 5-lipoxygenase has not only become unnecessary, but also deadly. (our-arthritis.com)
Atherosclerosis2
- For example, serum biomarkers, such as high sensitivity C-reactive protein (hsCRP) and cytokine levels, predict progression of atherosclerosis and risk of stroke. (medscape.com)
- 3-5 OXLAMs formed from LA activate NF-kB and increase proinflammatory cytokines, endothelial adhesion molecules, as well as chemokines, all of which are paramount in the formation of atherosclerosis. (bmj.com)
Receptors2
- Many of the yeast subunits are homologs to proteins in higher organisms that are found associated with specific nuclear receptors such as THYROID HORMONE RECEPTORS and VITAMIN D RECEPTORS . (nih.gov)
- When enough receptors are simultaneously activated by NTs, the neuron will either "fire" an electric current all over its surface membrane, if the transmitter/receptors are excitatory, or else the neuron will be inhibited from electrically discharging, if the NT/receptors are inhibitory. (antiaging-nutrition.com)
Phospholipase2
- Halobetasol propionate is thought to act by the induction of phospholipase A2 (PLA2) inhibitory proteins. (selleckchem.com)
- Finally, we found that running mice, as opposed to sedentary animals, showed significantly enhanced cortical expression of phospholipase A2 (PLA 2 ) protein, a signaling molecule required in the production of both AA and DHA. (cdc.gov)
GTPase1
- Rho GTPase activating protein 27. (gsea-msigdb.org)
Genes4
- In recent years, it is becoming an increasing focus of the role of the circadian clock in tumorigenesis, cancer hallmarks, therapeutic options, and discussions of how circadian clock genes can lead a new dimension in future medicine(4, 5). (researchsquare.com)
- Assessment of association between lipoxygenase genes variants in elderly Greek population and type 2 diabetes mellitus. (cdc.gov)
- Genes up-regulated in CD4 [GeneID=920] T cells activated by anti-CD3 and anti-CD28: IL-12 (2h) versus untreated (2h). (gsea-msigdb.org)
- But I'm also excited about all the work being done on genetics to take wild type genes and further tune not only the content of the protein, but sometimes the functionality. (foodnavigator-usa.com)
Tissue1
- It induces eosinophil synthesis and release of IL-8, an important chemotactic and activating factor for neutrophils and lymphocytes [ 22 , 23 ] which induces adhesion molecule expression also triggers the oxidative burst response, contributing to tissue damage [ 24 ]. (ispub.com)
IC501
- In the presence of CHIR-99021 the viability of the ES-D3 cells is reduced by 24.7% at 2.5 μM, 56.3% at 5 μM, 61.9% at 7.5 μM and 69.2% at 10 μM CHIR-99021 with an IC50 of 4.9 μM[3]. (dcchemicals.com)
Adaptor1
- DAB adaptor protein 2 [Source:HG. (gsea-msigdb.org)
MRNA1
- In human monocytes, 5-LO mRNA content increases on exposure to the synthetic glucocorticoid dexamethasone, which prompted us to hypothesize that glucocorticoids might increase 5-LO expression in the brain as well. (uab.edu)
Phosphorylation2
- Upon tyrosine phosphorylation, insulin receptor substrate proteins interact with specific SH2 DOMAIN containing proteins that are involved in insulin receptor signaling. (jefferson.edu)
- The binding of IQ 1 to PR72/130 leads to decreased phosphorylation of the coactivator protein p300 at Ser-89. (xcessbio.com)
Molecules3
- Among these proinflammatory molecules, interleukin-6, C-reactive protein, several adhesion molecules, CD40 ligand, osteoprotegerin and others are associated with the presence and progression of PAD. (bvsalud.org)
- effective( vivo) is required firmly by ester platelet apical-basolateral important proteins associated in brown regulators, and here generated by fundamental due endonucleases human in coordinate molecules incorporating the point, 5-phosphate and target. (evakoch.com)
- 19, for motifs) by specific transporters signaling sites in IL12 molecules cause Ca2+-activated from KFT because the Direct gene of the transport course binds synaptic at oxidation. (erik-mill.de)
Cytokines2
- Their recruitment, growth and survival are supported by cytokines and chemokines such as granulocyte-macrophage colony stimulating factor (GM-CSF), and interleukins (IL)- 3 and -5 [ 1 , 2 , 3 , 4 ]. (ispub.com)
- Eicosanoid biosynthesis begins when cell is activated by mechanical trauma, cytokines, growth factors or other stimuli. (chemeurope.com)
Induces1
- 5-8 LA also induces an inflammatory environment in endothelial cells that may increase the risk of coronary heart disease (CHD). (bmj.com)
Membrane3
- Using western immunoblotting, we also observed the concurrent translocation of 5-LO protein from cytosol to membrane, an indication of its activation. (uab.edu)
- approximately, the protein in acid side is enzymatic and, First to the central membrane of the Hamiltonian diseases, so following. (erik-mill.de)
- Stanford UniversityJay LeBoeuf is protein dyslexia, coupling, and loop in the hormones transport membrane. (erik-mill.de)
Kinase1
- A structurally-related group of signaling proteins that are phosphorylated by the INSULIN RECEPTOR PROTEIN-TYROSINE KINASE. (jefferson.edu)
Gene expression1
- TLR4 signaling mediated by the linker MyD88 activates the transcription factor nuclear factor kappa B (NF-κB), thereby inducing gene expression of pro-inflammatory factors like tumor necrosis factor (TNF), IL-6, and IL-1β ( Foley, 2015 ). (frontiersin.org)
Lipid1
- Ku happened at high concentrations just and didn't appear to be related to a primary inhibition of 5-LOX but instead because of a disruption of lipid rate of metabolism. (cancerhugs.com)
Synthase1
- Abstract A deep in silico investigation of various microsomal prostaglandin E2 synthase-1 (mPGES-1) protein systems is here reported using molecular dynamics (MD) simulations. (ebris.eu)
Localization1
- Scaffolding proteins that play an important role in the localization and activation of 5-LIPOXYGENASE. (bvsalud.org)
Nucleotide2
- Ischemic stroke risk in a southeastern Chinese population: Insights from 5-lipoxygenase activating protein and phosphodiesterase 4D single-nucleotide polymorphisms. (cdc.gov)
- 2012. Vitamin C deficiency activates the purine nucleotide cycle in zebrafish. . (oregonstate.edu)
Transmembrane protein1
- transmembrane protein 251 [Sourc. (gsea-msigdb.org)
Synaptic2
- Using this approach, we identified an exceptionally potent, orally active, neurotrophic molecule that facilitates memory in normal rodents, and prevents the loss of synaptic proteins and cognitive decline in a transgenic AD mouse model. (plos.org)
- Anaphylatoxin C5a activates C5a 6-phosphate( C5aR) binding in a synaptic cross-presentation of the TLR and ll Model-Based differentiation decarboxylation to neurogenesis. (evakoch.com)
Expression1
- However, CSE at 2.5% activated EOS as evidenced by ultrastructural degranulation: release of IL-8 and IL-6, and increased expression of the MAPK, c-Jun. (ispub.com)
Mitochondrial1
- Several NSAIDs indeed trigger increases in mobile [Ca2+] and oxidant tension (Tanaka research with cultured enterocytes, where high concentrations of diclofenac could actually trigger cyclosporin ACsensitive adjustments in calcein/Co2+ fluorescence, a recognized indicator from the mPT (LoGuidice by focusing on cyclophilin D (CypD), a mitochondrial matrix proteins and important regulator from the mPT. (cancerhugs.com)
Adverse effects1
- The prevalence of statin induced myotoxicity is between 1-5 %, but serious adverse effects are rare. (farmatid.no)
Excessive1
- How to prevent excessive 5-lipoxygenase production For millennia, ancient cultures acknowledged frankincense and myrrh resin both as a source of pleasant fragrances and as medicine against rheumatism, herpes, and gastrointestinal disorders. (our-arthritis.com)
Neurons2
- Previous studies have identified a potassium current in invertebrate neurons that is activated by volatile anesthetics. (asahq.org)
- ASP is also a major excitatory neurotransmitter, and ASP can activate neurons in place of GLU (1,2). (antiaging-nutrition.com)