prostaglandin endoperoxide synthases


Summary: Enzyme complexes that catalyze the formation of PROSTAGLANDINS from the appropriate unsaturated FATTY ACIDS, molecular OXYGEN, and a reduced acceptor.

Top Publications

  1. Elwood P, Gallagher A, Duthie G, Mur L, Morgan G. Aspirin, salicylates, and cancer. Lancet. 2009;373:1301-9 pubmed publisher
    ..We summarise evidence for the potential benefit of aspirin and natural salicylates in cancer prevention. Possible mechanisms of action and directions for further work are discussed, and implications for clinical practice are considered. ..
  2. Zhang F, Koyama Y, Sanuki R, Mitsui N, Suzuki N, Kimura A, et al. IL-17A stimulates the expression of inflammatory cytokines via celecoxib-blocked prostaglandin in MC3T3-E1 cells. Arch Oral Biol. 2010;55:679-88 pubmed publisher
    ..These results suggest that IL-17A stimulates the expression of bone resorption-related inflammatory cytokines through an autocrine mechanism involving celecoxib-blocked PGs, mainly PGE(2), in osteoblasts. ..
  3. Remacle C, Coosemans N, Jans F, Hanikenne M, Motte P, Cardol P. Knock-down of the COX3 and COX17 gene expression of cytochrome c oxidase in the unicellular green alga Chlamydomonas reinhardtii. Plant Mol Biol. 2010;74:223-33 pubmed publisher
    ..Concerning Cox3, its role in Chlamydomonas complex IV is similar to that of other eukaryotes although this subunit is encoded in the nuclear genome in the alga contrary to the situation found in all other organisms. ..
  4. Berry K, Henson P, Murphy R. Effects of acrolein on leukotriene biosynthesis in human neutrophils. Chem Res Toxicol. 2008;21:2424-32 pubmed
  5. Machado E, Carlos D, Louren o E, Souza G, Sorgi C, Silva E, et al. Cyclooxygenase-derived mediators regulate the immunological control of Strongyloides venezuelensis infection. FEMS Immunol Med Microbiol. 2010;59:18-32 pubmed publisher
  6. Vardanyan R, Vijay G, Nichol G, Liu L, Kumarasinghe I, Davis P, et al. Synthesis and investigations of double-pharmacophore ligands for treatment of chronic and neuropathic pain. Bioorg Med Chem. 2009;17:5044-53 pubmed publisher
    ..The absence of significant COX inhibitory properties could be explained by the required substitution of an acyl fragment in the indomethacin structure for 4-piperidyl. ..
  7. Ulmann L, Hirbec H, Rassendren F. P2X4 receptors mediate PGE2 release by tissue-resident macrophages and initiate inflammatory pain. EMBO J. 2010;29:2290-300 pubmed publisher
    ..Thus, P2X4Rs are specifically involved in inflammatory-mediated PGE2 production and might therefore represent useful therapeutic targets. ..
  8. Moore A, Ayoub S, Seed M. Cyclooxygenase enzymes and their products in the carrageenan-induced pleurisy in rats. Methods Mol Biol. 2010;644:201-5 pubmed publisher
  9. Zitova A, Hynes J, Kollar J, Borisov S, Klimant I, Papkovsky D. Analysis of activity and inhibition of oxygen-dependent enzymes by optical respirometry on the LightCycler system. Anal Biochem. 2010;397:144-51 pubmed publisher
    ..It is also applicable to other O(2)-dependent enzymes and enzymatic systems...

More Information


  1. de Godoy M, Rattan N, Rattan S. Arachidonic acid metabolites follow the preferential course of cyclooxygenase pathway for the basal tone in the internal anal sphincter. Am J Physiol Gastrointest Liver Physiol. 2009;296:G727-34 pubmed publisher
  2. Kalea A, Clark K, Schuschke D, Klimis Zacas D. Vascular reactivity is affected by dietary consumption of wild blueberries in the Sprague-Dawley rat. J Med Food. 2009;12:21-8 pubmed publisher
    ..We have concluded that diets enriched with blueberries, fed for 7 weeks in Sprague-Dawley rats, seem to affect NO metabolic pathways in the aorta at basal and stimulated levels. ..
  3. Abdellatif K, Chowdhury M, Dong Y, Das D, Yu G, Velazquez C, et al. Diazen-1-ium-1,2-diolated nitric oxide donor ester prodrugs of 5-(4-carboxymethylphenyl)-1-(4-methanesulfonylphenyl)-3-trifluoromethyl-1H-pyrazole and its aminosulfonyl analog: Synthesis, biological evaluation and nitric oxide release studies. Bioorg Med Chem. 2009;17:5182-8 pubmed publisher
  4. Tang E, Vanhoutte P. Endothelial dysfunction: a strategic target in the treatment of hypertension?. Pflugers Arch. 2010;459:995-1004 pubmed publisher
    ..Thus, endothelial dysfunction needs to be considered as a strategic target in the treatment of hypertension. ..
  5. Ansara A, Nisly S, Arif S, Koehler J, Nordmeyer S. Aspirin dosing for the prevention and treatment of ischemic stroke: an indication-specific review of the literature. Ann Pharmacother. 2010;44:851-62 pubmed publisher
    ..Aspirin has not yet been proven effective for primary prevention of strokes in men, and a minimum dose for these patients cannot be determined from the available data. ..
  6. Denniss S, Rush J. Impaired hemodynamics and endothelial vasomotor function via endoperoxide-mediated vasoconstriction in the carotid artery of spontaneously hypertensive rats. Am J Physiol Heart Circ Physiol. 2009;296:H1038-47 pubmed publisher
  7. Unsal Tan O, Ozden K, Rauk A, Balkan A. Synthesis and cyclooxygenase inhibitory activities of some N-acylhydrazone derivatives of isoxazolo[4,5-d]pyridazin-4(5H)-ones. Eur J Med Chem. 2010;45:2345-52 pubmed publisher
    ..It was observed that the compounds fit into, and interacted with, the hydrophobic parts which are common in the active pocket of COX-1 and COX-2 enzymes but could not fit to the area which is specific for COX-2 enzyme. ..
  8. Selg E, Andersson M, Låstbom L, Ryrfeldt A, Dahlen S. Two different mechanisms for modulation of bronchoconstriction in guinea-pigs by cyclooxygenase metabolites. Prostaglandins Other Lipid Mediat. 2009;88:101-10 pubmed publisher
    ..Whereas bronchoconstriction induced by LTD(4) was amplified predominantly by secondarily released TXA(2), that induced by PGD(2) was attenuated by bronchoprotective PGE(2) and PGI(2), presumably tonically produced in the airways. ..
  9. Yogi A, Callera G, Hipólito U, Silva C, Touyz R, Tirapelli C. Ethanol-induced vasoconstriction is mediated via redox-sensitive cyclo-oxygenase-dependent mechanisms. Clin Sci (Lond). 2010;118:657-68 pubmed publisher
    ..These findings identify putative molecular mechanisms whereby ethanol, at high concentrations, influences vascular reactivity. Whether similar phenomena occur in vivo at lower concentrations of ethanol remains unclear. ..
  10. Shrestha S, Kim Y. Various eicosanoids modulate the cellular and humoral immune responses of the beet armyworm, Spodoptera exigua. Biosci Biotechnol Biochem. 2009;73:2077-84 pubmed
  11. Eisenach J, Curry R, Rauck R, Pan P, Yaksh T. Role of spinal cyclooxygenase in human postoperative and chronic pain. Anesthesiology. 2010;112:1225-33 pubmed publisher
    ..Under the conditions of these studies, it seems that spinal cylcooxygenase activity does not contribute to chronic or postoperative pain. ..
  12. Zhou H, Liu W, Su Y, Wei Z, Liu J, Kolluri S, et al. NSAID sulindac and its analog bind RXRalpha and inhibit RXRalpha-dependent AKT signaling. Cancer Cell. 2010;17:560-73 pubmed publisher
    ..K-80003 displayed enhanced efficacy in inhibiting tRXRalpha-dependent AKT activation and tRXRalpha tumor growth in animals. ..
  13. Zambonin J, Engeham S, Campbell G, Ziabreva I, Beadle N, Taylor R, et al. Identification and investigation of mitochondria lacking cytochrome c oxidase activity in axons. J Neurosci Methods. 2010;192:115-20 pubmed publisher
    ..Our technique may be used to gain important clues to the underlying mechanisms of mitochondrial injury within axons in a number of CNS disorders and relevant animal models. ..
  14. Ji L, Li L, Schnitzer T, Du H, Prasad P. Intra-renal oxygenation in rat kidneys during water loading: effects of cyclooxygenase (COX) inhibition and nitric oxide (NO) donation. J Magn Reson Imaging. 2010;32:383-7 pubmed publisher
    ..This suggests that naproxcinod may have less nephrotoxicity and that the NO donating moiety partially compensates for the hemodynamic effects of prostaglandin inhibition by naproxen. ..
  15. Antonucci R, Fanos V. NSAIDs, prostaglandins and the neonatal kidney. J Matern Fetal Neonatal Med. 2009;22 Suppl 3:23-6 pubmed publisher
    ..The measurement of urinary PGE(2) may represent a non-invasive and sensitive tool to evaluate renal function, and thus should be implemented in the clinical management of newborns exposed to nephrotoxic insults. ..
  16. Beretta G, Rossoni G, Santagati N, Facino R. Anti-ischemic activity and endothelium-dependent vasorelaxant effect of hydrolysable tannins from the leaves of Rhus coriaria (Sumac) in isolated rabbit heart and thoracic aorta. Planta Med. 2009;75:1482-8 pubmed publisher
    ..The cardiovascular protective effect of RCLE seems to be due to an interplay of different factors: COX pathway activation, TNF-alpha inhibition, endothelial nitric oxide synthase (eNOS) activation, and free radical and ROS scavenging...
  17. Corriveau S, Rousseau E, Berthiaume M, Pasquier J. Lipoxygenase and cyclooxygenase inhibitors reveal a complementary role of arachidonic acid derivatives in pregnant human myometrium. Am J Obstet Gynecol. 2010;203:266.e1-7 pubmed publisher
    ..05). Finally, the combined inhibition of both COX and 12-LOX pathways resulted in additive tocolytic effects. 5- and 12-LOX pathways modulate human myometrium contractility. ..
  18. Holowatz L, Jennings J, Lang J, Kenney W. Ketorolac alters blood flow during normothermia but not during hyperthermia in middle-aged human skin. J Appl Physiol (1985). 2009;107:1121-7 pubmed publisher
  19. Hood W. Techniques used to characterize the binding of cyclooxygenase inhibitors to the cyclooxygenase active site. Methods Mol Biol. 2010;644:121-9 pubmed publisher
    ..With this in mind, we developed a radioligand-based binding assay for inhibitors of cyclooxygenase. ..
  20. Duggan K, Musee J, Marnett L. Peroxidase active site activity assay. Methods Mol Biol. 2010;644:55-65 pubmed publisher
    ..The first provides a continuous but indirect assay of peroxidase activity, whereas the second provides a discontinuous but direct assay. ..
  21. Mahat M, Kulkarni N, Vishwakarma S, Khan F, Thippeswamy B, Hebballi V, et al. Modulation of the cyclooxygenase pathway via inhibition of nitric oxide production contributes to the anti-inflammatory activity of kaempferol. Eur J Pharmacol. 2010;642:169-76 pubmed publisher
    ..These results partially explain the pharmacological efficacy of flavonoids in general and kaempferol in particular as anti-inflammatory compounds. ..
  22. Kaltoft N, Tilotta M, Witte A, Osbak P, Poulsen S, Bindslev N, et al. Prostaglandin E2-induced colonic secretion in patients with and without colorectal neoplasia. BMC Gastroenterol. 2010;10:9 pubmed publisher
    ..This indicates that increased indomethacin-sensitive mechanisms in colonic mucosa from neoplasia diseased patients are not related to differences in functional expression of EP receptor subtypes. ..
  23. Herath S, Lilly S, Fischer D, Williams E, Dobson H, Bryant C, et al. Bacterial lipopolysaccharide induces an endocrine switch from prostaglandin F2alpha to prostaglandin E2 in bovine endometrium. Endocrinology. 2009;150:1912-20 pubmed publisher
  24. Colleran P, Li Z, Yang H, Laughlin M, Terjung R. Vasoresponsiveness of collateral vessels in the rat hindlimb: influence of training. J Physiol. 2010;588:1293-307 pubmed publisher
    ..If these findings were applicable to patients with PAI, they could contribute to an improved collateral vessel function and enhance exercise tolerance during routine physical activity. ..
  25. Sinha R, Pathak A, Mohan V, Babu S, Pal A, Khare D, et al. Evidence of a bigenomic regulation of mitochondrial gene expression by thyroid hormone during rat brain development. Biochem Biophys Res Commun. 2010;397:548-52 pubmed publisher
    ..These results thus indicate an integrated nuclear-mitochondrial cross talk in regulation of mitochondrial transcription by TH during brain development. ..
  26. Boutaud O, Oates J. Study of inhibitors of the PGH synthases for which potency is regulated by the redox state of the enzymes. Methods Mol Biol. 2010;644:67-90 pubmed publisher
    ..Accordingly, analysis of the action of these inhibitors requires consideration of assay conditions that take into account the factors that control hydroperoxide concentrations, both in studies with purified enzymes and in cells. ..
  27. Lim Y, Na H, Yun Y, Choi I, Oh J, Rhee J, et al. Suppressive effects of ginsan on the development of allergic reaction in murine asthmatic model. Int Arch Allergy Immunol. 2009;150:32-42 pubmed publisher
    ..Lastly, ginsan inhibited the allergic reaction aggravated by COX inhibitor (indomethacin). Ginsan has anti-asthmatic effects, which seem to be partially mediated by enhancing the synthesis of COX gene products. ..
  28. Syam A, Sadikin M, Wanandi S, Rani A. Molecular mechanism on healing process of peptic ulcer. Acta Med Indones. 2009;41:95-8 pubmed
    ..g EGF-R, c-fos, c-jun, egr-1, Sp-1, TFF-2/SP. Intermediate response genes are activated for 6 hours to 2 days, eg EGF, bFGF, PDGF and VEGF. Late response genes are activated for 14 days, e.g. HGF, ITF, c-met/HGF-R. ..
  29. Kuklina E, Shirshev S. Role of cyclooxygenase in the chorionic gonadotropin regulation of human neutrophil activity. Bull Exp Biol Med. 2009;147:213-6 pubmed
    ..These data indicate that realization of the suppressive effects of chorionic gonadotropin in the neutrophils is partially linked with activation of cyclooxygenase (both the constitutive and inducible forms of the enzyme). ..
  30. Wang Z, Ma W, Chabot J, Quirion R. Cell-type specific activation of p38 and ERK mediates calcitonin gene-related peptide involvement in tolerance to morphine-induced analgesia. FASEB J. 2009;23:2576-86 pubmed publisher
  31. Lau M, Wong A, Leung P. Gonadotropins induce tumor cell migration and invasion by increasing cyclooxygenases expression and prostaglandin E(2) production in human ovarian cancer cells. Endocrinology. 2010;151:2985-93 pubmed publisher
    ..These data show that COX-1 and COX-2 play essential roles in gonadotropin-induced migration and invasion. ..
  32. Ratz P, Speich J. Evidence that actomyosin cross bridges contribute to "passive" tension in detrusor smooth muscle. Am J Physiol Renal Physiol. 2010;298:F1424-35 pubmed publisher
  33. Wu G, Tsai A, Kulmacz R. Cyclooxygenase competitive inhibitors alter tyrosyl radical dynamics in prostaglandin H synthase-2. Biochemistry. 2009;48:11902-11 pubmed publisher
    ..This dramatic modulation of tyrosyl radical stability by cyclooxygenase site ligands suggests a mechanism for regulating the reactivity of PGHS tyrosyl radicals with cellular antioxidants. ..
  34. Bachi A, Kim F, Nonogaki S, Carneiro C, Lopes J, Jasiulionis M, et al. Leukotriene B4 creates a favorable microenvironment for murine melanoma growth. Mol Cancer Res. 2009;7:1417-24 pubmed publisher
  35. Cook V, Jones Shults J, McDowell M, Campbell N, Davis J, Marshall J, et al. Anti-inflammatory effects of intravenously administered lidocaine hydrochloride on ischemia-injured jejunum in horses. Am J Vet Res. 2009;70:1259-68 pubmed publisher
    ..Coadministration of lidocaine with flunixin ameliorated the flunixin-induced increase in mucosal neutrophil counts. ..
  36. Versteilen A, Korstjens I, Musters R, Groeneveld A, Sipkema P. Role of cyclooxygenase and derived reactive oxygen species in rho-kinase-mediated impairment of endothelium-dependent vasodilation and blood flow after ischemia-reperfusion of the rat kidney. Nephron Exp Nephrol. 2010;114:e1-6 pubmed publisher
    ..In contrast, the vasodilatory effect of rho-kinase inhibition may be partly mediated by decreasing ROS, unrelated to COX and resultant vasoconstricting prostanoids. ..
  37. Telleria Diaz A, Schmidt M, Kreusch S, Neubert A, Schache F, Vazquez E, et al. Spinal antinociceptive effects of cyclooxygenase inhibition during inflammation: Involvement of prostaglandins and endocannabinoids. Pain. 2010;148:26-35 pubmed publisher
  38. De Seranno S, d Anglemont de Tassigny X, Estrella C, Loyens A, Kasparov S, Leroy D, et al. Role of estradiol in the dynamic control of tanycyte plasticity mediated by vascular endothelial cells in the median eminence. Endocrinology. 2010;151:1760-72 pubmed publisher
    ..Taken together, our findings show that estradiol controls the dialog between endothelial cells and astroglia to regulate neuroglial plasticity in the neuroendocrine brain...
  39. Wu D, Wang X, Zhou J, Yuan J, Cui B, An R, et al. Traditional Chinese formula, lubricating gut pill, improves loperamide-induced rat constipation involved in enhance of Cl- secretion across distal colonic epithelium. J Ethnopharmacol. 2010;130:347-53 pubmed publisher
    ..LGP enhances Cl(-) secretion that is mostly mediated through the release of cyclooxygenase metabolites, by which provided an osmotic force for the subsequent laxative action observed in the rat constipation model. ..
  40. Biondo G, Dias Melicio L, Bordon Graciani A, Acorci Valério M, Soares A. Paracoccidioides brasiliensis uses endogenous and exogenous arachidonic acid for PGE x production. Mycopathologia. 2010;170:123-30 pubmed publisher
    ..The data provide evidence that P. brasiliensis produces prostaglandin-like molecules by metabolizing either endogenous or exogenous AA. Moreover, the results suggest the involvement of these mediators on fungal viability. ..
  41. Sharma B, Singh P, Shekhawat M, Pilania P. A rationale for the activity profile of benzenesulfonamide derivatives as cyclooxygenase (COX) inhibitors. Eur J Med Chem. 2010;45:2389-95 pubmed publisher
  42. Miclescu A, Gordh T. Nitric oxide and pain: 'Something old, something new'. Acta Anaesthesiol Scand. 2009;53:1107-20 pubmed publisher
    ..Inhibitors of NO synthesis may have analgesic effects and would be of interest for treating inflammatory and neuropathic pain. Unfortunately, only a few of these compounds have reached the stage of clinical pain trials. ..
  43. Alagha A, Moman E, Adamo M, Nolan K, Chubb A. Design, synthesis and evaluation of aspirin analogues having an additional carboxylate substituent for antithrombotic activity. Bioorg Med Chem Lett. 2009;19:4213-6 pubmed publisher
    ..One of these, an ester derivative which unlike acetylsalicylic acid is non-acidic, may act as useful lead compound for further exploitation of this approach. ..
  44. Afanas ev I. Superoxide and nitric oxide in senescence and aging. Front Biosci (Landmark Ed). 2009;14:3899-912 pubmed
  45. Cheng S, Chuang C, Wen Z, Wang S, Chiou S, Hsu C, et al. Bioactive norditerpenoids from the soft coral Sinularia gyrosa. Bioorg Med Chem. 2010;18:3379-86 pubmed publisher
    ..6+/-4.6%, 66.9+/-5.2%, 10.2+/-5.1%, 17.4+/-7.2%, 47.2+/-11.9%, and 56.3+/-5.1%, respectively) by LPS stimulation. Compound 8 showed significant antiviral activity against HCMV (human cytomegalovirus) cells with an IC(50) of 1.9microg/mL. ..
  46. Bonaventura D, Lunardi C, Rodrigues G, Neto M, Vercesi J, de Lima R, et al. Endothelium negatively modulates the vascular relaxation induced by nitric oxide donor, due to uncoupling NO synthase. J Inorg Biochem. 2009;103:1366-74 pubmed publisher
    ..This enhancement in O(2)(-) concentration induces COX activation, producing TXA(2), which negatively modulates the rat aorta relaxation induced by the NO donor TERPY. ..
  47. Fu L, Longhurst J. Bradykinin and thromboxane A2 reciprocally interact to synergistically stimulate cardiac spinal afferents during myocardial ischemia. Am J Physiol Heart Circ Physiol. 2010;298:H235-44 pubmed publisher
  48. Shimizu T, Yokotani K. Brain cyclooxygenase and prostanoid TP receptors are involved in centrally administered epibatidine-induced secretion of noradrenaline and adrenaline from the adrenal medulla in rats. Eur J Pharmacol. 2009;606:77-83 pubmed publisher
  49. Xu G, Liu F, Ao G, He S, Ju M, Zhao Y, et al. Anti-inflammatory effects and gastrointestinal safety of NNU-hdpa, a novel dual COX/5-LOX inhibitor. Eur J Pharmacol. 2009;611:100-6 pubmed publisher
    ..These data indicate that NNU-hdpa comprises a novel class of dual inhibitors of COX and 5-LOX having therapeutic potential with an enhanced gastric safety profile. ..
  50. De Armas R, Durand K, Guillaudeau A, Weinbreck N, Robert S, Moreau J, et al. mRNA levels of enzymes and receptors implicated in arachidonic acid metabolism in gliomas. Clin Biochem. 2010;43:827-35 pubmed publisher
    ..mRNA levels of enzymes and receptors implicated both in lipoxygenase and cyclooxygenase pathways differed significantly in gliomas according to the histological type. ..
  51. Hamza M, Dionne R. Mechanisms of non-opioid analgesics beyond cyclooxygenase enzyme inhibition. Curr Mol Pharmacol. 2009;2:1-14 pubmed
  52. Angelini C, Bello L, Spinazzi M, Ferrati C. Mitochondrial disorders of the nuclear genome. Acta Myol. 2009;28:16-23 pubmed
    ..Future developments will show that many neurodegenerative disorders are due to mutations of nuclear genes controlling mitochondrial function, fusion and fission. ..
  53. Tsai A, Kulmacz R. Prostaglandin H synthase: resolved and unresolved mechanistic issues. Arch Biochem Biophys. 2010;493:103-24 pubmed publisher
    ..The interconversions among radicals on Tyr385, on Tyr504, and on arachidonate, and their relationships to regulation and inactivation of the cyclooxygenase, are still under active investigation for both PGHS isozymes. ..