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  • arachidonic acid
  • you will see arachidonic acid (gray structure surrounded with dots made of mostly carbon and hydrogen) that is bound inside the active site of Cox-1. (davidson.edu)
  • The S -nitrosylation detection and subsequent kinetic investigations into the arachidonic acid (AA) oxidation of COX enzymes indicate that NO S -nitrosylates both COX-1 and COX-2 in an oxygen-dependent manner, but enhances only the dioxygenase activity of COX-2. (rsc.org)
  • HO2) residue to arachidonic acid (i.e. 5Z,8Z,11Z,14Z-eicosatetraenoic acid) at carbon 5 of its 1,4 diene group (i.e. its 5Z,8Z double bonds) to form 5(S)-hydroperoxy-6E,8Z,11Z,14Z-eicosatetraenoic acid (i.e. 5S-HpETE). (wikipedia.org)
  • aspirin
  • To investigate the impact of blood type, functional polymorphism (T-1676C) of the COX-1 gene promoter, and clinical factors on the development of peptic ulcer during cardiovascular prophylaxis with low-dose aspirin. (hindawi.com)
  • In a case-control study including 111 low-dose aspirin users with peptic ulcers and 109 controls (asymptomatic aspirin users), the polymorphism (T-1676C) of the COX-1 gene promoter was genotyped, and blood type, H pylori status, and clinical factors were assessed. (hindawi.com)
  • The C-1676T polymorphism in the COX-1 gene promoter is not a risk factor for ulcer formation during treatment with low-dose aspirin. (hindawi.com)
  • Low-dose aspirin (75-325 mg/day) is widely used in the prevention of myocardial infarction or ischemic stroke [ 1 ]. (hindawi.com)
  • We examined whether competitive enzyme kinetics describe COX-1 inhibition by aspirin and HAPR and if they are compatible with results obtained experimentally. (ahajournals.org)
  • We have developed an enzyme kinetic model of the aspirin/NSAID interaction at COX-1 using mathematical modelling and have varied enzyme kinetic parameters to predict the occurrence and the extent of HAPR. (ahajournals.org)
  • Both enzyme kinetic modelling and experimental results suggest competitive antagonism of NSAID and aspirin at COX-1 as a cause for HAPR, possibly resulting in cardiovascular events. (ahajournals.org)
  • synthase
  • Neutralization of plasma PGE 2 with specific antibodies did not ameliorate the anorexia, and genetic deletion of microsomal PGE synthase-1 (mPGES-1) affected neither anorexia nor tumor growth. (diva-portal.org)
  • Microsomal PGE 2 synthase-1 (mPGES-1) is the dominant and best-studied terminal PGE 2 synthase in brain. (jneurosci.org)
  • NO, a highly reactive small molecule produced within mammalian cells by the enzyme NO synthase (NOS) including iNOS (inducible NOS), eNOS (endothelial NOS) and nNOS (neuronal NOS), was initially reported by Needleman's group that can activate cyclooxygenase. (rsc.org)
  • Its abundant production during blood clotting, the presence of cyclooxygenases and to a lesser extent thromboxane synthase in a wide range of cell types and tissue, and its production by other pathways imply that 12-HHT has one or more important bioactivities relevant to clotting and, perhaps, other responses. (wikipedia.org)
  • inhibit
  • AZT (zidovudine) and other chain-terminating nucleoside analogues used to inhibit HIV-1 reverse transcriptase in the treatment of HIV/AIDS. (wikipedia.org)
  • enzymes
  • There are two enzymes of COX, COX 1 and COX 2. (abcam.com)
  • These observations suggest that COX-enzymes, most likely COX-1, are involved in cancer-elicited anorexia and weight loss, but that these phenomena occur independently of host mPGES-1, PGE 2 and neuronal EP 4 signaling. (diva-portal.org)
  • There was a compensatory up-regulation of COX-2, accompanied by the activation of the NF-κB pathway, and also an increase in the upstream cPLA 2 and sPLA 2 enzymes. (wiley.com)
  • Additionally, COX-1 deficiency can affect the expression of reciprocal and coupled enzymes, COX-2, Ca 2+ -dependent PLA 2 , and terminal mPGES-2, to overcome defects in brain AA cascade. (wiley.com)
  • COX enzymes are important drug targets for the non-steroidal anti-inflammatory drugs. (rsc.org)
  • irreversible
  • 22 Recently, we found that the first irreversible hydrogen transfer step in COX-2 catalysis altered along with oxygen variations, 23 suggesting that the oxygen concentration has a huge impact on enzyme activity. (rsc.org)
  • Ibuprofen
  • In 2006, ibuprofen lysine was approved in the US by the Food and Drug Administration (FDA) for closure of patent ductus arteriosus in premature infants weighing between 500 and 1,500 grams (1 and 3 lb), who are no more than 32 weeks gestational age when usual medical management (such as fluid restriction, diuretics, and respiratory support) is not effective. (wikipedia.org)
  • Roles
  • 1-3 They have been found to play great roles in certain diseases, including cancer, 4 and nervous system 5 and apoptosis-related diseases. (rsc.org)
  • COX2
  • Earlier studies with COX knockout (COXko) mice suggested that COX2 was more important for hypophagia than COX1. (aspetjournals.org)
  • These results suggest that shortly after IL-1β administration, COX1 is the major enzyme involved in the reduction of milk intake, whereas at later times COX2 is more important, paralleling its induction. (aspetjournals.org)
  • substrate
  • The solution viscosity, deuterium kinetic isotope effect (KIE), and oxygen-18 KIE experiments further demonstrate that NO activates COX-2 by altering the protein conformation to stimulate substrate association/product release and by accelerating the rate of hydrogen abstraction from AA by catalytic tyrosine radicals. (rsc.org)
  • species
  • However, the identity of the PGs and the PG producing cyclooxygenase (COX) species responsible for cancer anorexia-cachexia is unknown. (diva-portal.org)
  • 20 It was suggested that the complex chemistry of NO species (NOx) and the crude enzyme preparations result in dichotomous effects with respect to COX activation by NO. 21 Nevertheless, the mechanism of NO activation has not been understood yet and more in-depth kinetic investigations into the interaction between NO and COX are urgently needed. (rsc.org)
  • whereas
  • Taken together, our results suggest that COX-2 is necessary for optimal CD8 + T cell responses to L. monocytogenes , whereas COX-1 is detrimental. (jimmunol.org)
  • We found that brain PGE 2 concentration was significantly increased, whereas thromboxane B2 (TXB 2 ) concentration was decreased in COX-1 -/- mice. (wiley.com)
  • When milk intake was measured 30 to 40 min after IL-1β, COX1ko mice showed an attenuated response, whereas COX2ko mice responded more like wild-type animals. (aspetjournals.org)
  • By contrast, 90 to 120 min after IL-1β COX1ko mice responded normally, whereas COX2ko mice showed only small responses. (aspetjournals.org)
  • dioxygenase activity
  • In addition, we demonstrated that the dioxygenase activity of COX-2 can be analyzed independently of peroxidase activity by adding sufficient phenol, which acts as a sacrificed reductant, 22,23 at a concentration of up to 2.5 mM. (rsc.org)
  • immunoreactivity
  • 9 Iseki has reported the localisation of COX-1 and COX-2 to mucous cells of normal rat gastric mucosa 10 but these data have not been confirmed by others who have been unable to detect COX-2 immunoreactivity in normal rat stomach. (bmj.com)
  • The present experiments fill this void in showing that COX-1 immunoreactivity (IR) and mRNA are detectable in identified PVCs and parenchymal microglia under basal conditions and is robustly expressed in these and ECs 1-3 h after intravenous injection of LPS (2 μg/kg). (jneurosci.org)
  • inactivates
  • Acetylation of Cox-1 (or Cox-2) irreversibly inactivates the enzyme. (davidson.edu)
  • Though a body of evidence indicated that NO elicits up-regulation of COX activity, 13-16 a large number of reports support the idea that NO inactivates COX 17-19 or has little effect on enzyme activity under certain conditions. (rsc.org)
  • NSAID
  • 2 Misoprostol (a PGE 1 analogue) prevents NSAID associated peptic ulceration and its complications in humans. (bmj.com)
  • peptic
  • Univariate analysis showed no significant differences in genotype frequencies of the COX-1 gene at position -1676 between the peptic ulcer group and control group. (hindawi.com)
  • stimuli
  • 1 Recent pain research has focused on neural-immune interactions in both the periphery and the spinal cord that induce hypersensitivity to thermal and mechanical stimuli. (asahq.org)
  • pathways
  • 12 Since then, numerous studies have shown that there is crosstalk between the NOS and COX pathways. (rsc.org)
  • induction
  • CONCLUSION Angiogenesis by HuGE cells in vitro was associated with induction of functional COX-2 expression. (bmj.com)
  • 4 Current dogma is that COX-1 is responsible for PG synthesis in normal gastric mucosa in order to maintain mucosal homoeostasis 5 and that COX-2 is expressed by normal gastric mucosa at low levels, 6 with induction of expression during ulcer healing 7 8 or following endotoxin exposure. (bmj.com)
  • 13 It is established that human umbilical vein endothelial cells (HUVECs) express COX-1 constitutively and COX-2 following induction by factors such as interleukin 1 and phorbol ester in vitro. (bmj.com)
  • COX-2 induction is readily demonstrable in ECs and/or PVCs after such challenges, and its expression correlates with several acute phase endpoints across a range of experimental conditions. (jneurosci.org)
  • activity
  • In contrast, loss of COX-1 activity improved immunity to L. monocytogenes . (jimmunol.org)
  • Use of pharmacotherapies that spare COX-2 activity and the production of PGE 2 like acetaminophen will be critical for the generation of optimal antitumor responses using L. monocytogenes . (jimmunol.org)
  • a GC-rich core region including the Sp1/Egr-1 sites may be critical for basal 5-LO promoter activity. (wikipedia.org)
  • HUMAN
  • AIMS To investigate COX expression by human gastric endothelial (HuGE) cells during angiogenesis in vitro. (bmj.com)
  • 8 9 11 There are no published studies of COX localisation in human gastric mucosa. (bmj.com)
  • Herein, recombinant human COX-1 and COX-2 were prepared and treated with NO donors individually under anaerobic and aerobic conditions. (rsc.org)
  • extent
  • 6 This could be a result of differences in expression of the COX-1 or it could be that the increase in COX-1 expression in the younger animals occurs to a similar extent, but does not produce hypersensitivity after incision. (asahq.org)
  • production
  • Thus, COX is a key enzyme in the production of inflammatory agents and is the target of intense research and drug discovery activities. (abcam.com)
  • Capillary endothelial cells are a major site of PGE 2 production in canine fundic mucosa 12 and COX-1 has been localised to endothelium of submucosal blood vessels in rat gastric mucosa. (bmj.com)
  • Overall, our data suggest that COX-1 and COX-2 play a distinct role in brain PG biosynthesis, with basal PGE 2 production being metabolically coupled with COX-2 and TXB 2 production being preferentially linked to COX-1. (wiley.com)
  • 2002
  • Two cell types of the cerebral vasculature, endothelial cells (ECs) and perivascular cells (PVCs) (a subset of brain resident macrophages) have been implicated in the transduction of circulating immune signals presented by IL-1β or LPS ( Schiltz and Sawchenko, 2002 ). (jneurosci.org)
  • results
  • RESULTS Under normal culture conditions (30% serum), HuGE cells expressed COX-1 and low levels of COX-2. (bmj.com)
  • indicate
  • Confocal and electron microscopic analyses indicate distinct cellular/subcellular localizations of COX-1-IR in the three cell types. (jneurosci.org)