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Gene Review

PTGS1  -  prostaglandin-endoperoxide synthase 1...

Homo sapiens

Synonyms: COX-1, COX1, COX3, Cyclooxygenase-1, PCOX1, ...
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Disease relevance of PTGS1


Psychiatry related information on PTGS1

  • Of particular importance has been the investigation of COX-1 and -2 isozymic functions in cancer, dysregulation of inflammation, and Alzheimer's disease [7].
  • We would like to discuss recent developments reinforcing anti-inflammatory drugs as therapeutic in the treatment of AD amyloidosis, and the relevance of understanding the role of COX and other inflammatory mediators in AD neuropathology and the clinical progression of AD dementia [8].
  • Cyclooxygenase-1 and -2 in brains of patients who died with sporadic Creutzfeldt-Jakob disease [9].
  • In eight healthy subjects, a freeze lesion was induced and mechanical pain thresholds (MPT) were tested for 5h following administration of the non-selective COX inhibitor diclofenac (75mg), the COX-2-selective inhibitor parecoxib (40mg) or placebo in a randomized, double-blind cross-over study [10].
  • The mechanism of binding of different nonsteroidal anti-inflammatory drugs to the cyclooxygenase active site of cyclooxygenase-2 (COX-2) has been studied by means of a wide range of theoretical techniques including molecular dynamics and free energy calculations [11].

High impact information on PTGS1

  • We further examine the evidence for independent signaling by PGHS-1 and PGHS-2, and the complex mechanisms for regulation of PGHS-2 gene expression [12].
  • PGHS-1 and 2 are of particular interest because they are the major targets of nonsteroidal anti-inflammatory drugs (NSAIDs) including aspirin, ibuprofen, and the new COX-2 inhibitors [12].
  • Prostanoids are the cyclooxygenase metabolites of arachidonic acid and include prostaglandin (PG) D(2), PGE(2), PGF(2alpha), PGI(2), and thromboxne A(2) [13].
  • To explore the role of cyclooxygenase (COX) in endothelial cell migration and angiogenesis, we have used two in vitro model systems involving coculture of endothelial cells with colon carcinoma cells [3].
  • Cyclooxygenase regulates colon carcinoma-induced angiogenesis by two mechanisms: COX-2 can modulate production of angiogenic factors by colon cancer cells, while COX-1 regulates angiogenesis in endothelial cells [3].

Chemical compound and disease context of PTGS1


Biological context of PTGS1

  • PTGS1 mRNA abundance, measured by real-time RT-PCR, increased in the amnion and the placenta during the last third of gestation [19].
  • Within the Minnesota polyp case-control study, patients with colorectal adenomatous (n = 521) or hyperplastic (n = 194) polyps and n = 621 polyp-free controls were genotyped for four PTGS1 polymorphisms (R8W, L15-L16del, P17L, L237M); these had been predicted to affect protein function based on sequence-homology software [1].
  • The structures of exons in the human prostaglandin-endoperoxide-synthase-2 gene were also similar to those of the human prostaglandin-endoperoxide-synthase-1 gene (PTGS1) [20].
  • Cyclooxygenase-1 [prostaglandin H synthase 1 gene (PTGS1)] was tested as a plausible candidate for the unknown gene because of its role in primary hemostasis [2].
  • The position of PTGS1 was refined on the CHLC chromosome 9 linkage map using the new markers scored in four Centre d'Etude du Polymorphisme Humain families and multipoint linkage analysis [2].

Anatomical context of PTGS1


Associations of PTGS1 with chemical compounds

  • CONCLUSION(S): Monkey OSE expresses mRNA for PTGS1, PTGS2, and all PGE synthases and produces PGE(2) both before and 36 hours after hCG [21].
  • Basal COX activity, assessed by quantitating immunoreactive PGE2 synthesized from arachidonic acid, was twofold less (P < 0.05) in F-IPF than F-nl [5].
  • The present study was undertaken to determine if there is differential expression of COX in colonic tumors in azoxymethane-treated rats [23].
  • Cyclooxygenase (COX)-1 or -2 and prostaglandin (PG) synthases catalyze the formation of various PGs and thromboxane (TX) A(2) [24].
  • These findings suggests that (i) aspirin and NCX-4016 trigger ATL formation in humans, (ii) celecoxib inhibits ATL formation and exacerbates the mucosal injury caused by low doses of aspirin, and (iii) the NO-donating moiety of NCX-4016 protects the gastric mucosa even in the presence of suppression of COX-1 and COX-2 [25].
  • Inhibition studies with indomethacin demonstrated that the P17L and G230S variants had significantly lower IC50 values compared to wild-type, suggesting these variants significantly increase COX-1 sensitivity to indomethacin inhibition [26].
  • In an effort to understand the structural impact of chirality on COX-1 selectivity, the crystal structures of ovine COX-1 in complexes with an enantiomeric pair of these indomethacin ethanolamides were determined at resolutions between 2.75 and 2.85 A [27].

Physical interactions of PTGS1


Enzymatic interactions of PTGS1


Regulatory relationships of PTGS1


Other interactions of PTGS1


Analytical, diagnostic and therapeutic context of PTGS1


  1. Polymorphisms in PTGS1 (=COX-1) and risk of colorectal polyps. Ulrich, C.M., Bigler, J., Sparks, R., Whitton, J., Sibert, J.G., Goode, E.L., Yasui, Y., Potter, J.D. Cancer Epidemiol. Biomarkers Prev. (2004) [Pubmed]
  2. Characterization of the human prostaglandin H synthase 1 gene (PTGS1): exclusion by genetic linkage analysis as a second modifier gene in familial thrombosis. Scott, B.T., Hasstedt, S.J., Bovill, E.G., Callas, P.W., Valliere, J.E., Wang, L., Wu, K.K., Long, G.L. Blood Coagul. Fibrinolysis (2002) [Pubmed]
  3. Cyclooxygenase regulates angiogenesis induced by colon cancer cells. Tsujii, M., Kawano, S., Tsuji, S., Sawaoka, H., Hori, M., DuBois, R.N. Cell (1998) [Pubmed]
  4. Expression of cyclooxygenase-1 and cyclooxygenase-2 in human breast cancer. Hwang, D., Scollard, D., Byrne, J., Levine, E. J. Natl. Cancer Inst. (1998) [Pubmed]
  5. Cultured lung fibroblasts isolated from patients with idiopathic pulmonary fibrosis have a diminished capacity to synthesize prostaglandin E2 and to express cyclooxygenase-2. Wilborn, J., Crofford, L.J., Burdick, M.D., Kunkel, S.L., Strieter, R.M., Peters-Golden, M. J. Clin. Invest. (1995) [Pubmed]
  6. Alternative splicing of cyclooxygenase-1 gene: altered expression in leucocytes from patients with bronchial asthma and association with aspirin-induced 15-HETE release. Kowalski, M.L., Borowiec, M., Kurowski, M., Pawliczak, R. Allergy (2007) [Pubmed]
  7. Cyclooxygenase isozymes: the biology of prostaglandin synthesis and inhibition. Simmons, D.L., Botting, R.M., Hla, T. Pharmacol. Rev. (2004) [Pubmed]
  8. From epidemiology to therapeutic trials with anti-inflammatory drugs in Alzheimer's disease: the role of NSAIDs and cyclooxygenase in beta-amyloidosis and clinical dementia. Pasinetti, G.M. J. Alzheimers Dis. (2002) [Pubmed]
  9. Cyclooxygenase-1 and -2 in brains of patients who died with sporadic Creutzfeldt-Jakob disease. Deininger, M.H., Bekure-Nemariam, K., Trautmann, K., Morgalla, M., Meyermann, R., Schluesener, H.J. J. Mol. Neurosci. (2003) [Pubmed]
  10. Pharmacological and histopathological characterization of a hyperalgesia model induced by freeze lesion. Schmidtko, A., Burian, M., Altis, K., Hardt, K., Angioni, C., Schmidt, R., Podda, M., Geisslinger, G. Pain (2007) [Pubmed]
  11. Theoretical studies on the inhibition mechanism of cyclooxygenase-2. Is there a unique recognition site? Soliva, R., Almansa, C., Kalko, S.G., Luque, F.J., Orozco, M. J. Med. Chem. (2003) [Pubmed]
  12. Cyclooxygenases: structural, cellular, and molecular biology. Smith, W.L., DeWitt, D.L., Garavito, R.M. Annu. Rev. Biochem. (2000) [Pubmed]
  13. Prostanoid receptors: structures, properties, and functions. Narumiya, S., Sugimoto, Y., Ushikubi, F. Physiol. Rev. (1999) [Pubmed]
  14. Cyclooxygenase-1 is up-regulated in cervical carcinomas: autocrine/paracrine regulation of cyclooxygenase-2, prostaglandin e receptors, and angiogenic factors by cyclooxygenase-1. Sales, K.J., Katz, A.A., Howard, B., Soeters, R.P., Millar, R.P., Jabbour, H.N., Soeters, R.P. Cancer Res. (2002) [Pubmed]
  15. Selective inhibition of cyclooxygenase-2 suppresses growth and induces apoptosis in human esophageal adenocarcinoma cells. Souza, R.F., Shewmake, K., Beer, D.G., Cryer, B., Spechler, S.J. Cancer Res. (2000) [Pubmed]
  16. Synergistic effects of new chemopreventive agents and conventional cytotoxic agents against human lung cancer cell lines. Soriano, A.F., Helfrich, B., Chan, D.C., Heasley, L.E., Bunn, P.A., Chou, T.C. Cancer Res. (1999) [Pubmed]
  17. Association between Cyclooxygenase expression and colorectal adenoma characteristics. Einspahr, J.G., Krouse, R.S., Yochim, J.M., Danenberg, P.V., Danenberg, K.D., Bhattacharyya, A.K., Martínez, M.E., Alberts, D.S. Cancer Res. (2003) [Pubmed]
  18. EBV suppresses prostaglandin E2 biosynthesis in human monocytes. Savard, M., Bélanger, C., Tremblay, M.J., Dumais, N., Flamand, L., Borgeat, P., Gosselin, J. J. Immunol. (2000) [Pubmed]
  19. Prostaglandin H2 synthase-1 and -2 expression in guinea pig gestational tissues during late pregnancy and parturition. Welsh, T., Mitchell, C.M., Walters, W.A., Mesiano, S., Zakar, T. J. Physiol. (Lond.) (2005) [Pubmed]
  20. Characterization of the human gene (PTGS2) encoding prostaglandin-endoperoxide synthase 2. Kosaka, T., Miyata, A., Ihara, H., Hara, S., Sugimoto, T., Takeda, O., Takahashi, E., Tanabe, T. Eur. J. Biochem. (1994) [Pubmed]
  21. Prostaglandin-endoperoxide synthase (PTGS1 and PTGS2) expression and prostaglandin production by normal monkey ovarian surface epithelium. Cabrera, R.A., Dozier, B.L., Duffy, D.M. Fertil. Steril. (2006) [Pubmed]
  22. Genetic model of selective COX2 inhibition reveals novel heterodimer signaling. Yu, Y., Fan, J., Chen, X.S., Wang, D., Klein-Szanto, A.J., Campbell, R.L., FitzGerald, G.A., Funk, C.D. Nat. Med. (2006) [Pubmed]
  23. Increased cyclooxygenase-2 levels in carcinogen-induced rat colonic tumors. DuBois, R.N., Radhika, A., Reddy, B.S., Entingh, A.J. Gastroenterology (1996) [Pubmed]
  24. Cyclooxygenase-2 expression is induced during human megakaryopoiesis and characterizes newly formed platelets. Rocca, B., Secchiero, P., Ciabattoni, G., Ranelletti, F.O., Catani, L., Guidotti, L., Melloni, E., Maggiano, N., Zauli, G., Patrono, C. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  25. Interaction of a selective cyclooxygenase-2 inhibitor with aspirin and NO-releasing aspirin in the human gastric mucosa. Fiorucci, S., Santucci, L., Wallace, J.L., Sardina, M., Romano, M., del Soldato, P., Morelli, A. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  26. Identification and functional characterization of polymorphisms in human cyclooxygenase-1 (PTGS1). Lee, C.R., Bottone, F.G., Krahn, J.M., Li, L., Mohrenweiser, H.W., Cook, M.E., Petrovich, R.M., Bell, D.A., Eling, T.E., Zeldin, D.C. Pharmacogenet. Genomics (2007) [Pubmed]
  27. Structural basis of enantioselective inhibition of cyclooxygenase-1 by S-alpha-substituted indomethacin ethanolamides. Harman, C.A., Turman, M.V., Kozak, K.R., Marnett, L.J., Smith, W.L., Garavito, R.M. J. Biol. Chem. (2007) [Pubmed]
  28. Partnering between monomers of cyclooxygenase-2 homodimers. Yuan, C., Rieke, C.J., Rimon, G., Wingerd, B.A., Smith, W.L. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  29. Correlation of expression of cyclooxygenase-2, vascular endothelial growth factor, and peroxisome proliferator-activated receptor delta with head and neck squamous cell carcinoma. Jaeckel, E.C., Raja, S., Tan, J., Das, S.K., Dey, S.K., Girod, D.A., Tsue, T.T., Sanford, T.R. Arch. Otolaryngol. Head Neck Surg. (2001) [Pubmed]
  30. The structure of mammalian cyclooxygenases. Garavito, R.M., Mulichak, A.M. Annual review of biophysics and biomolecular structure. (2003) [Pubmed]
  31. Expression of the ELAV-like protein HuR is associated with higher tumor grade and increased cyclooxygenase-2 expression in human breast carcinoma. Denkert, C., Weichert, W., Winzer, K.J., Müller, B.M., Noske, A., Niesporek, S., Kristiansen, G., Guski, H., Dietel, M., Hauptmann, S. Clin. Cancer Res. (2004) [Pubmed]
  32. B cell differentiation and interleukin 2 (IL2): corticosteroids interact with monocytes to enhance the effect of IL2. Emilie, D., Karray, S., Crevon, M.C., Vazquez, A., Galanaud, P. Eur. J. Immunol. (1987) [Pubmed]
  33. Mutational analysis of the role of the distal histidine and glutamine residues of prostaglandin-endoperoxide synthase-2 in peroxidase catalysis, hydroperoxide reduction, and cyclooxygenase activation. Landino, L.M., Crews, B.C., Gierse, J.K., Hauser, S.D., Marnett, L.J. J. Biol. Chem. (1997) [Pubmed]
  34. Role of Asn-382 and Thr-383 in activation and inactivation of human prostaglandin H synthase cyclooxygenase catalysis. Bambai, B., Rogge, C.E., Stec, B., Kulmacz, R.J. J. Biol. Chem. (2004) [Pubmed]
  35. Cyclooxygenase inhibitors suppress aromatase expression and activity in breast cancer cells. Díaz-Cruz, E.S., Shapiro, C.L., Brueggemeier, R.W. J. Clin. Endocrinol. Metab. (2005) [Pubmed]
  36. Vascular endothelial growth factor upregulates constitutive cyclooxygenase 1 in primary bovine and human endothelial cells. Bryant, C.E., Appleton, I., Mitchell, J.A. Life Sci. (1998) [Pubmed]
  37. COX-1 and COX-2 contributions to basal and IL-1 beta-stimulated prostanoid synthesis in human neonatal cerebral microvascular endothelial cells. Parfenova, H., Levine, V., Gunther, W.M., Pourcyrous, M., Leffler, C.W. Pediatr. Res. (2002) [Pubmed]
  38. Interferon-gamma and interleukin 4 inhibit interleukin 1beta-induced delayed prostaglandin E(2)generation through suppression of cyclooxygenase-2 expression in human fibroblasts. Hayashi, Y., Kobayashi, M., Kuwata, H., Atsumi, G., Deguchi, K., Feng Wei, X., Kudo, I., Hasegawa, K. Cytokine (2000) [Pubmed]
  39. Expression of 5-lipoxygenase and cyclooxygenase pathway enzymes in nasal polyps of patients with aspirin-intolerant asthma. Adamjee, J., Suh, Y.J., Park, H.S., Choi, J.H., Penrose, J.F., Lam, B.K., Austen, K.F., Cazaly, A.M., Wilson, S.J., Sampson, A.P. J. Pathol. (2006) [Pubmed]
  40. Prostaglandin e synthase, a terminal enzyme for prostaglandin E2 biosynthesis. Kudo, I., Murakami, M. J. Biochem. Mol. Biol. (2005) [Pubmed]
  41. Regulation of cytosolic phospholipase A2, cyclooxygenase-1 and -2 expression by PMA, TNFalpha, LPS and M-CSF in human monocytes and macrophages. Jiang, Y.J., Lu, B., Choy, P.C., Hatch, G.M. Mol. Cell. Biochem. (2003) [Pubmed]
  42. Up-regulation of cyclooxygenase 2 gene expression correlates with tumor angiogenesis in human colorectal cancer. Cianchi, F., Cortesini, C., Bechi, P., Fantappiè, O., Messerini, L., Vannacci, A., Sardi, I., Baroni, G., Boddi, V., Mazzanti, R., Masini, E. Gastroenterology (2001) [Pubmed]
  43. Expression of cyclooxygenase-1 and -2 in human colorectal cancer. Sano, H., Kawahito, Y., Wilder, R.L., Hashiramoto, A., Mukai, S., Asai, K., Kimura, S., Kato, H., Kondo, M., Hla, T. Cancer Res. (1995) [Pubmed]
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