Prostaglandin Endoperoxide Synthase (Total 148437 Papers Found)

Lipopolysaccharide (LPS) produces prostaglandins (PGs) concomitant to eliciting macrophage migration. We evaluated the role of PGs in initiating the migration of macrophages, especially focusing on PGD(2) and PGE(2). In RAW264.7 macrophages, cyclooxygenase (COX)-2 inhibitor, CAY10404 [3-(4-methylsulphonylphenyl)-4-phenyl-5-trifluoromethylisoxazole], completely inhibited LPS-mediated migration at 4 h (early phase) but only partially inhibited the migration at 8 h (late phase), suggesting the pres ...
Production of plasminogen activator (PA) by granulosa cells (GC) and its stimulation by gonadotropins led to the suggestion that PA is involved in ovulation. However, whereas only LH may be regarded as the ovulation-inducing hormone in the rat, FSH was found to be much more potent than LH in enhancing PA production by GC. Assuming that the entire follicular wall, rather than isolated GC, is involved in follicular rupture, we have examined activity of PA in intact follicles. LH (NIH-LH-S23) was 5 ...
Cyclooxygenase (COX) exists in two isoforms, COX-1 and COX-2, COX-1 is present and is constitutively expressed in most cells and tissues, whereas COX-2 is felt to principally mediate inflammation. However, this distinction appears to be challenged by recent observations. This review addresses the roles of COX-1 and COX-2 isoforms in physiologic and pathophysiologic states and reviews potential therapeutic roles for selective COX inhibitors. ...
PURPOSE We examined whether a continuing medical education intervention increased general practitioners' ability to select the proper pharmacological treatment for patients with osteoarthritis. SUBJECTS AND METHODS Eight towns in Quebec, Canada were randomly allocated to one of four intervention options, workshop and decision tree, workshop, decision tree, or no intervention. All general practitioners practicing in each town were eligible to participate. We evaluated all dispensed prescription ...
Cyclooxygenase (COX)-1- and COX-2-derived prostaglandins are implicated in the development and progression of several malignancies. We have recently demonstrated that treatment of ovarian carcinoma cells with endothelin-1 (ET-1) induces expression of both COX-1 and COX-2, which contributes to vascular endothelial growth factor (VEGF) production. In this study, we show that in HEY and OVCA 433 ovarian carcinoma cells, ET-1, through the binding with ETA receptor (ETAR), induces prostaglandin E2 (P ...
Accumulating evidence indicates cyclooxygenase (COX) 1 and COX2 differentially regulate cardiovascular and renal function. We have demonstrated previously in mice that COX2 inhibition enhances angiotensin II-induced hypertension, and COX1 inhibition attenuates the pressor effect of angiotensin II. To further elucidate the mechanism underlying the functional difference of COX1 versus COX2 inhibition, the present studies examined the prostaglandin (PG) profiles derived in COX1- or COX2-inhibited m ...
Anandamide (AEA), an endogenous cannabinoid receptor agonist, is a potent vasodilator in the cerebral microcirculation. AEA is converted to arachidonic acid (AA) by fatty acid amidohydrolase (FAAH), and the conversion of AA to prostaglandins has been proposed as a potential mechanism for the vasodilation. Although AEA stimulated prostaglandin production by mouse cerebral microvascular endothelial cells, no [(3)H]prostaglandins were produced when these cells were incubated with [3H]AEA. Incubatio ...
The molecular mechanism of the synergistic platelet inhibition by activators of adenylate cyclase and guanylate cyclase in human platelets was investigated. The adenylate cyclase activators iloprost and prostaglandin E1 and the guanylate cyclase activator 3-morpholino-syndnonimine (SIN-1) dose-dependently inhibited thrombin-induced aggregation of washed human platelets. Furthermore, SIN-1 at a concentration inhibiting platelet aggregation by only 10% shifted the IC50 values of iloprost and prost ...
Symptoms of cardiovascular diseases are frequently found in patients with hypothyroidism and hyperthyroidism. However, it is unknown whether arachidonic acid metabolites, the potent mediators in cardiovascular system, are involved in cardiovascular disorders caused by hyperthyroidism and hypothyroidism. To answer this question, serum levels of arachidonic acid metabolites in human subjects with hypothyroidism, hyperthyroidism and mice with hypothyroidism or thyroid hormone treatment were determi ...
Our previous studies have shown that the anti-asthma traditional Chinese medicine herbal formula ASHMI (anti-asthma simplified herbal medicine intervention) inhibits acetylcholine-induced contractions of tracheal rings from ovalbumin-sensitized and naive mice in a β-adrenoceptor-independent manner. We sought to determine whether acute in vivo ASHMI administration inhibits airway hyperreactivity (AHR) in a murine model of allergic asthma and acetylcholine-induced tracheal ring constriction ex vi ...
Different VOx/TiO2 catalyst have been catalytically tested and studied by in situ-spectroscopic methods (FT-IR, UV/vis, EPR) in the oxyhydrative scission (OHS) of 1-butene and n-butane to acetic acid (AcOH). While 1-butene OHS follows the sequence butane → butoxide → ketone → AcOH/acetate with a multitude of side products also formed, n-butane OHS leads to AcOH, COx and H2O only. Water vapour in the feed improves AcOH selectivity by blocking adsorption sites for acetate. The admixture of S ...
We investigated whether the mitogenic response induced by local mast-cell secretion in the rat mesentery was affected by suppression of phospholipase A2, lipoxygenase, or cyclooxygenase in arachidonic acid metabolism. Enzyme inhibitor was given in a single intravenous dose 5 min before intraperitoneal injection of the mast-cell secretagogue 48/80. Mepacrine, a phospholipase A2 inhibitor, suppressed the generation of both leukotrienes (SRS) and prostaglandins (PG), whereas the lipoxygenase inhibi ...
CI-986 (5-[3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl]-1,3,4-thiadiazole-2(3H)- thione-2-hydroxy-N,N,N-trimethylethanaminium salt) is a novel anti-inflammatory compound classified as a dual inhibitor of cyclooxygenase and 5-lipoxygenase. Studies were undertaken to characterize the preclinical toxicology of the compound. CI-986 was administered to rats for 2 weeks (0, 50, 250, 750, and 1500 mg/kg) or 13 weeks (0, 20, 250, 500, and 1000 mg/kg), dogs for 2 weeks (0, 50, 150, and 500 mg/kg) or 13 we ...
Heme oxygenase the rate-limiting step in the degradation of heme to bilirubin, generates carbon monoxide. This gaseous molecule plays important roles in neuronal signaling and modulation of vascular tone. Additionally, carbon monoxide is involved in some pathological conditions (e.g., ischemia, endotoxic shock, excitotoxicity) as a protective or toxic factor. Bilirubin, another heme metabolite, exhibits intriguing biological activities as an antioxidant, an antimutagen, and an anti-complement ag ...
The inhibition of photosynthesis by O(2) in air-grown Chlorella pyrenoidosa was investigated using three experimental techniques (artificial leaf, aqueous method, and O(2) electrode) to measure carbon assimilation. CO(2) response curves were determined under different O(2), pH, and temperature conditions. Regardless of the experimental technique and condition, O(2) inhibition was not evident until a concentration of 50% was reached; V(max) values were reduced whereas K(m) (CO(2)) values were una ...
Although leaves of Curcuma mangga and Curcuma longa are used in food preparations, the bioactive components in it are not known. In this study, antioxidant, antiinflammatory and anticancer activities of leave extracts and its isolates were investigated using established bioassay procedures in our laboratory. The leaf extracts of both plants gave similar bioassay and chromatographic profiles. The methanolic and water extracts of C. mangga (CMM and CMW) and C. longa (CLM and CLW), at 100 μg/mL, i ...
BACKGROUND Food processing effects can modify protein functional properties. However, protein was oxidized inevitably by lipid peroxidation during food processing. Acrolein, a primary by-product of lipid peroxidation, can modify the structural and functional properties of protein. The aim of the research was to analyze the effect of acrolein on allergenicity of TM, a major allergen in shrimp. RESULTS The overall allergenic effects of acrolein-treated TM were evaluated using female BALB/c mice ...
In order to study the hormonal control mechanisms of cervical maturation, we investigated cyclooxygenase and 5-lipoxygenase inhibitors-induced changes in the distribution of glycosaminoglycans (GAG) in pregnant Wistar rat uterine cervices at term. The GAG were measured in a control (n = 11), in a Diclofenac (cyclooxygenase inhibitor) treated group (n = 8), in a BW 755C (dual inhibitor of cyclooxygenase and 5-lipoxygenase) treated group (n = 6), and a L 651392 (5-lipoxygenase inhibitor) treated g ...
Overexpression of cyclooxygenase (COX)-2 has been implicated in the development of cancer. This study aimed to evaluate the relationship between genetic variants in COX-2 promoter interacting with Helicobacter pylori and the susceptibility to gastric cancer (GC). Three COX-2 polymorphisms -1290A>G (rs689465), -1195G>A (rs689466), and -765G>C (rs20417) were genotyped in 323 GC patients and 944 controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by logistic regr ...
The effect of 15-Mt-PGF2 alpha on CCl4-induced injury of primary cultured hepatocytes was studied. 15-Mt-PGF2 alpha treatment (2 mg/L) significantly decreased CCl4 (10 mmol/L)-induced damages of primary cultured rat heptocytes as indicated by decreases GPT and GOT leakage and LPO production. 15-Mt-PGF2 alpha significantly promoted 3H-uridine incorporation into RNA and [3H]-thymidine incorporation into DNA of the rat hepatocytes. Cytopathology study showed that 15-Mt-PGF2 alpha attenuated damages ...
 One major role of alveolar macrophages is the production of eicosanoids, which modulate immune and inflammatory processes in the lung. In this study, the effects were investigated of cadmium ions on the secretion of leukotriene (LT)B4 and prostaglandin (PG)E2, predominant products of lipoxygenase and cyclooxygenase, respectively. Cd2+ had an inhibitory effect on the secretion of LTB4 and PGE2 in response to A23187 stimulation at concentrations >3× 10-5 M. This effect can be explained by ...
Fragile histidine triad (FHIT) gene deletions are among the earliest and most frequent events in carcinogenesis, particularly in carcinogen-exposed tissues. Though FHIT has been established as an authentic tumor suppressor, the mechanism underlying tumor suppression remains opaque. Most experiments designed to clarify FHIT function have analyzed the consequence of re-expressing FHIT in FHIT-negative cells. However, carcinogenesis occurs in cells that transition from FHIT-positive to FHIT-negativ ...
Chondrocyte apoptosis contributes to the disruption of cartilage integrity in osteoarthritis (OA). Recently, we reported that activation of volume-sensitive Cl- current (ICl,vol) mediates cell shrinkage, triggering apoptosis in rabbit articular chondrocytes. A cyclooxygenase (COX) blocker is frequently used for the treatment of OA. In the present study, we examined in vitro effects of selective blockers of COX on the TNFα-induced activation of ICl,vol in rabbit chondrocytes using the patch-clam ...
Traditionally, heme oxygenase (HO) activity in tissue preparations is determined spectrophoto-metrically by measuring the rate of bilirubin production, a two-enzyme reaction sequence. The adequacy of this method depends upon the presence of excess biliverdin reductase and the transparency of samples. In order to study the effects of inhibitors (e.g. Sn-heme, 25 uM), and inducers (e.g. CoCl2, 250 umoles/kg) of HO, the first enzyme in the sequence, independent of possible, effects on other parts o ...
Caffeine, one of the most commonly prescribed drugs in preterm neonates, is given in standard or suprapharmacologic doses. Although known as a diuretic, its effects in the neonatal kidneys are not well studied. We tested the hypothesis that neonatal intermittent hypoxia (IH) and high caffeine doses (HCD) alter renal regulators of vasomotor tone and water balance. Newborn rats were randomized to room air, hyperoxia, or IH and treated with standard or high caffeine doses; or placebo saline. Renal ...
We compared the variability in degree and recovery from steady-state inhibition of cyclooxygenase (COX)-1 and COX-2 ex vivo and in vivo and platelet aggregation by naproxen sodium at 220 versus 440 mg b.i.d. and low-dose aspirin in healthy subjects. Six healthy subjects received consecutively naproxen sodium (220 and 440 mg b.i.d.) and aspirin (100 mg daily) for 6 days, separated by washout periods of 2 weeks. COX-1 and COX-2 inhibition was determined using ex vivo and in vivo indices of enzymat ...
Colorectal carcinoma is one of the commonest solid organ tumors in the world and its prevalence appears to be increasing in Asia. Recently, there has been much interest in various chemotherapeutic agents for the management of this condition, in particular nonsteroidal anti-inflammatory drugs (NSAIDs). There is a large amount of data that suggest traditional NSAIDs, as well as the new cyclooxygenase (COX)-2 selective inhibitors such as rofecoxib and celecoxib, have a role in the setting of primar ...
Geranylgeranyl diphosphate (GGPP) synthase was purified to homogeneity from bovine brain in a one-step affinity column procedure. For the construction of the affinity column, a farnesyl diphosphate (FPP) analog, O-(6-amino-1-hexyl)-P-farnesylmethyl phosphonophosphate, was synthesized and linked to the spacer of the matrix of Affigel 10 via the amino group. The native enzyme appeared to be homooligomer (150-195 kDa) with a molecular mass of the monomer of 37.5 kDa. The pI for the enzyme was 6.2. ...
Colorectal cancer (CRC) is the one of the leading causes of cancer-related deaths in the world. CRC is responsible for more than 600,000 deaths annually and incidence rates are increasing in most of the developing countries. Epidemiological and laboratory investigations suggest that environmental factors such as western style dietary habits, tobacco-smoking, and lack of physical activities are considered as risks for CRC. Molecular pathobiology of CRC implicates pro-inflammatory conditions to pr ...
Recent studies have reported that expression of monocyte chemoattractant protein 1 (MCP-1) and its receptor (CCR2) and CD40 ligation on mesenchymal cells play important roles in tumor development. Cyclooxygenase 2 (COX-2) has also been shown to contribute to tumor angiogenesis. We examined the interaction between MCP-1 and CD40 ligation in mesenchymal cells in gastric cancer to determine the effect of these factors on vascular endothelial growth factor (VEGF) production via upregulation of COX-2 ...
The effect of low blood flow at onset of moderate-intensity exercise on the rate of rise in muscle oxygen uptake was examined. Seven male subjects performed a 3.5-min one-legged knee-extensor exercise bout (24 +/- 1 W, mean +/- SD) without (Con) and with (double blockade; DB) arterial infusion of inhibitors of nitric oxide synthase (N(G)-monomethyl-l-arginine) and cyclooxygenase (indomethacin) to inhibit the synthesis of nitric oxide and prostanoids, respectively. Leg blood flow and leg oxygen d ...
Activated blood platelets and macrophages metabolize prostaglandin H(2) into thromboxane A(2) and 12(S)-hydroxyheptadeca-5Z, 8E, 10E-trienoic acid (12-HHT) in an equimolar ratio through the action of thromboxane synthase. Although it has been shown that 12-HHT is abundant in tissues and bodily fluids, this compound has long been viewed as a by-product lacking any specific function. We show that 12-HHT is a natural ligand for leukotriene B(4) (LTB(4)) receptor-2 (BLT2), a G protein-coupled recept ...
The regulation of enzyme activity through the transient formation of multiprotein assemblies plays an important role in the control of biosynthetic pathways. One of the first regulatory complexes to be discovered was cysteine synthase (CS), formed by the pyridoxal 5'-phosphate-dependent enzyme O-acetylserine sulfhydrylase (OASS) and serine acetyltransferase (SAT). These enzymes are at the branch point of the sulfur, carbon, and nitrogen assimilation pathways. Understanding the mechanism of compl ...
Oxidative stress is implicated as one of the major underlying mechanisms behind many acute and chronic diseases, and involved in normal aging. However, the measurement of free radicals or their end products is complicated. Thus, proof of association of free radicals in pathologic conditions has been absent. Isoprostanes are prostaglandin-like bioactive compounds that are biosynthesized in vivo independent of cyclooxygenases, principally through free-radical catalyzation of arachidonic acid. Isop ...
Heme oxygenase (HO)-1 is an oxygen-dependent enzyme that may regulate vascular tone and cell proliferation through the production of carbon monoxide (CO). We tested the hypothesis that HO-1 is upregulated in the lung in chronic hypoxia by exposing male Sprague-Dawley rats to 17,000 feet (395 Torr) for 0, 1, 3, 7, 14, or 21 days. After exposure, blood gases, carboxyhemoglobin (COHb) levels, and hematocrit were measured, and the lungs were either inflation fixed for immunohistochemistry or frozen ...
We recently developed prostaglandin E1 (PGE1)-encapsulated nanoparticles, prepared with a poly(lactide) homopolymer (PLA, Mw = 17,500) and monomethoxy poly(ethyleneglycol)-PLA block copolymer (PEG-PLA) (NP-L20). In this study, we tested whether the accelerated blood clearance (ABC) phenomenon is observed with NP-L20 and other PEG-modified PLA-nanoparticles in rats. The plasma levels of PGE1 and anti-PEG IgM antibody were determined by EIA and ELISA, respectively. Second injections of NP-L20 ...
The primary lesion in Parkinson's disease is the death of dopaminergic neurons in the substantia nigra. The role of cyclooxygenase (COX)-2 in the etiology of Parkinson's disease was explored using COX-2 gene knockout mice. Mortality after injection of 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP, a chemical known to cause parkinsonism in humans) in heterozygous COX-2-deficient mice was lower than that in wild-type mice. The number of tyrosine hydroxylase immunoreactive neurons in the subst ...
Non-steroidal anti-inflammatory drugs (NSAIDs) and selective cyclooxygenase-2 (COX-2) inhibitors (COXIBs) induce cancer cell apoptosis via several signaling pathways. There is evidence that they induce colon cancer cell apoptosis by suppressing peroxisome proliferator-activated receptor delta (PPARdelta) through inhibition of COX-2-derived prostacyclin (PGI2). PGI2 activates PPARdelta resulting in binding of PPARdelta to specific PPAR response elements (PPRE) of target genes. We have identified ...
  • J Slapke, L. Jaeger,
  • Zeitschrift fur die gesamte innere Medizin und ihre Grenzgebiete
  • 1979
Asthma, caused by analgesics, a relatively frequent phenomenon in bronchial asthma conditioned by infection, often remains unrecognized and is then sometimes a danger of high degree for these patients. Pathogenetically, the asthma caused by analgesics perhaps does not underlie an immunological mechanism, but an induced by analgesics prostaglandin-E-synthesis inhibition. For this speak the results of skin tests, of the LTT with analgesics and of IgE concentration measurements. Concomitant phenome ...
OBJECTIVE To study the effects of c9, t11-conjugated linoleic acid (c9, t11-CLA) on the critical enzyme (COX-2) and its product - prostaglandin E2 (PGE2) of linoleic acid metabolism path in human gastric adenocarcinoma cell line (SGC-7901). METHODS Expression of COX-2 mRNA and protein were measured by reverse transcription polymerase chain reaction (RT-PCR) and Western blot, PGE2 was determined by radioimmunoassay (RIA). RESULTS At the concentrations of 25, 50, 100, 200 pmol/L, c9, t11-CLA s ...
While platelets have been shown to be capable of supplying prostaglandin (PG) H2 to endothelial cells in culture for PGI2 synthesis, endothelial cells have been shown unable to supply PGH2 to platelets for thromboxane (TX) A2 synthesis. We incubated rings of the bovine coronary artery (BCAR) with human platelets treated with aspirin (to inhibit cyclooxygenase) or CGS 13080 (to inhibit TXA2 synthase) in the presence of 20 microM arachidonic acid. BCAR, with damaged endothelium, produced significa ...
We found that prostaglandin (PG) D(2) production was induced through transcriptional activation of cyclooxygenase (COX)-2 and lipocalin-type PGD synthase (L-PGDS) genes under serum-starved conditions in human brain-derived TE671 cells. Analysis of promoter and intron regions of the human L-PGDS gene demonstrated that an atypical E-box within intron 4 mediated serum starvation-induced up-regulation of L-PGDS gene expression. The results of electrophoretic mobility shift assay and chromatin immuno ...
Prostaglandin E(2) (PGE(2)) positively regulates bone resorption and formation mainly mediated through the EP(4) receptor, a subtype of PGE(2) receptors. ONO-4819, an EP(4) receptor-selective agonist, has been shown to increase bone volume, density, and strength; however, the mechanism of these effects has yet to be fully elucidated. To explore this matter, ONO-4819 (10μg/kg) was injected into intact rats twice a day for 5weeks, and their bones were then analyzed by morphological techniques. Th ...
After a single in vivo application of 20 nmol of the 'complete' tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) or of the 'incomplete' promoter 12-O-retinoylphorbol-13-acetate (RPA) to the back skin of mice, a major arachidonic acid metabolite (AAMX) was found in cell-free epidermal preparations after addition of arachidonic acid (AA). Studies with cyclooxygenase and lipoxygenase inhibitors indicated that this metabolite is a lipoxygenase product. The metabolite has been purified by se ...
Cyclooxygenase catalysis by prostaglandin H synthase (PGHS)-1 and -2 involves reaction of a peroxide-induced Tyr385 radical with arachidonic acid (AA) to form an AA radical that reacts with O(2). The potential for isomeric AA radicals and formation of an alternate tyrosyl radical at Tyr504 complicate analysis of radical intermediates. We compared the EPR spectra of PGHS-1 and -2 reacted with peroxide and AA or specifically deuterated AA in anaerobic, single-turnover experiments. With peroxide-tr ...
Human solid tumors remain latent in the absence of angiogenesis since it is a critical process for their further growth and progression. Experimental evidence suggests that targeting tumor angiogenesis may be a novel strategy to check tumor growth and metastases. Recent studies suggest that several bioactive food components can suppress tumor growth by inhibiting angiogenesis. This suppression occurs because of a direct effect on the tumor, as well as a direct effect on vascular endothelial cell ...
The oocyte-cumulus complex (25 oocytes per 250 microL medium) produced prostaglandin-F2 alpha (PGF2 alpha) and PGE2 during maturation, immediately following fertilization and for at least 48 h after fertilization. The data suggest that PG production is important in the development of the oocyte; addition of PGE2 (5 ng mL-1) to the fertilization medium increased the rate of cleavage and groups of oocytes with low cleavage rates produced far less PG than groups with high cleavage rates. Measuremen ...
Phosphatase and tensin homologue deleted on chromosome 10 (PTEN) is a tumor suppressor. Although it is well known to have various physiological roles in cancer, its inhibitory effect on inflammation remains poorly understood. In the present study, a human PTEN gene was fused with PEP-1 peptide in a bacterial expression vector to produce a genetic in-frame PEP-1-PTEN fusion protein. The expressed and purified PEP-1-PTEN fusion protein were transduced efficiently into macrophage Raw 264.7 cells in ...
Metabolites of arachidonic acid are known to play an important part in the pathogenesis of organ injury in endotoxic shock. We compared the effects of the classical cyclooxygenase inhibitor aspirin with that of the dual cyclooxygenase and lipoxygenase inhibitor ketoprofen on the behavior of platelets tagged with 111In-labeled oxine in multiple organs during endotoxin shock. Three groups of sheep (n = 7 in each) were anesthetized before being subjected to endotoxin shock. Group E had no drug trea ...