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Gene Review

Ptgs1  -  prostaglandin-endoperoxide synthase 1

Mus musculus

Synonyms: COX-1, COX1, Cox-1, Cox-3, Cox1, ...
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Disease relevance of Ptgs1

  • In contrast, Ptgs1-deficient mice had pancreatitis and pulmonary inflammation, which was as severe or, in some instances, more severe than in the wild-type mice [1].
  • We conclude that radiation injury results in increased Cox-1 levels in crypt stem cells and their progeny, and that PGE2 produced through Cox-1 promotes crypt stem cell survival and proliferation [2].
  • The role of COX in acute pancreatitis and pancreatitis-associated lung injury is not known [1].
  • Collectively, these findings demonstrate the coordinated regulation of fetal and maternal PGs at the time of birth but raise concern regarding the use of selective COX inhibitors for the management of preterm labor [3].
  • To establish a CRC liver metastasis model, we implanted mouse colon tumor MC-26 cells into the splenic subcapsule of BALB/c mice, after which mice were given either standard chow or chow containing the cyclooxygenase (COX)-2-specific inhibitor rofecoxib, alone or in combination with the standard antineoplastic agents, 5-fluoruracil or irinotecan [4].

Psychiatry related information on Ptgs1


High impact information on Ptgs1

  • Homozygous Ptgs1 mutant mice survive well, have no gastric pathology, and show less indomethacin-induced gastric ulceration than wild-type mice, even though their gastric prostaglandin E2 levels are about 1% of wild type [8].
  • PGHS1 and PGHS2 coexist in the vasculature and in macrophages, and are upregulated together in inflammatory tissues such as rheumatoid synovia and atherosclerotic plaque [9].
  • They were developed with the rationale of conserving the anti-inflammatory and analgesic actions of traditional nonsteroidal anti-inflammatory drugs (tNSAIDs) while sparing the ability of PGHS1-derived prostaglandins to afford gastric cytoprotection [9].
  • Here we show that PAF induces pulmonary edema through two mechanisms: acid sphingomyelinase (ASM)-dependent production of ceramide, and activation of the cyclooxygenase pathway [10].
  • The initial cyclooxygenase reaction converts arachidonic acid (which is achiral) to prostaglandin G2 (which has five chiral centres) [11].

Chemical compound and disease context of Ptgs1


Biological context of Ptgs1


Anatomical context of Ptgs1


Associations of Ptgs1 with chemical compounds


Regulatory relationships of Ptgs1

  • PGHS-2 enzyme was expressed maximally after 24 h of activation whereas PGHS-1 was not influenced [26].
  • It has long been proposed that the inhibition of the 5-LO could enhance the COX pathway leading to an increased PG generation [27].
  • TNF-alpha preferentially promoted gene expression of cyclooxygenase (COX)-2 without affecting that of COX-1 [28].
  • We herein demonstrate that PGE2 in stimulated P388D1 cells is accounted for by the inducible cyclooxygenase (COX)-2 [29].
  • These cells exhibit increased basal PG production, which is due to a constitutively stimulated cytosolic phospholipase A2 and enhanced basal expression of the remaining COX isozyme [30].

Other interactions of Ptgs1


Analytical, diagnostic and therapeutic context of Ptgs1


  1. Cyclooxygenase-2 gene disruption attenuates the severity of acute pancreatitis and pancreatitis-associated lung injury. Ethridge, R.T., Chung, D.H., Slogoff, M., Ehlers, R.A., Hellmich, M.R., Rajaraman, S., Saito, H., Uchida, T., Evers, B.M. Gastroenterology (2002) [Pubmed]
  2. Crypt stem cell survival in the mouse intestinal epithelium is regulated by prostaglandins synthesized through cyclooxygenase-1. Cohn, S.M., Schloemann, S., Tessner, T., Seibert, K., Stenson, W.F. J. Clin. Invest. (1997) [Pubmed]
  3. Coordinated regulation of fetal and maternal prostaglandins directs successful birth and postnatal adaptation in the mouse. Reese, J., Paria, B.C., Brown, N., Zhao, X., Morrow, J.D., Dey, S.K. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  4. Inhibition of cyclooxygenase-2 by rofecoxib attenuates the growth and metastatic potential of colorectal carcinoma in mice. Yao, M., Kargman, S., Lam, E.C., Kelly, C.R., Zheng, Y., Luk, P., Kwong, E., Evans, J.F., Wolfe, M.M. Cancer Res. (2003) [Pubmed]
  5. Protective effect of cyclooxygenase-2 (COX-2) inhibitors but not non-selective cyclooxygenase (COX)-inhibitors on ethanol withdrawal-induced behavioural changes. Dhir, A., Naidu, P.S., Kulkarni, S.K. Addiction biology. (2005) [Pubmed]
  6. Cycloxygenase-2 activity promotes cognitive deficits but not increased amyloid burden in a model of Alzheimer's disease in a sex-dimorphic pattern. Melnikova, T., Savonenko, A., Wang, Q., Liang, X., Hand, T., Wu, L., Kaufmann, W.E., Vehmas, A., Andreasson, K.I. Neuroscience (2006) [Pubmed]
  7. A possible role of endogenously formed cerebral prostaglandins in the development of adaptive protection against cerebral hypoxia/ischemia in mice. Masuda, Y., Ochi, Y., Ochi, Y., Kadokawa, T. Methods and findings in experimental and clinical pharmacology. (1987) [Pubmed]
  8. Prostaglandin synthase 1 gene disruption in mice reduces arachidonic acid-induced inflammation and indomethacin-induced gastric ulceration. Langenbach, R., Morham, S.G., Tiano, H.F., Loftin, C.D., Ghanayem, B.I., Chulada, P.C., Mahler, J.F., Lee, C.A., Goulding, E.H., Kluckman, K.D., Kim, H.S., Smithies, O. Cell (1995) [Pubmed]
  9. 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]
  10. PAF-mediated pulmonary edema: a new role for acid sphingomyelinase and ceramide. Göggel, R., Winoto-Morbach, S., Vielhaber, G., Imai, Y., Lindner, K., Brade, L., Brade, H., Ehlers, S., Slutsky, A.S., Schütze, S., Gulbins, E., Uhlig, S. Nat. Med. (2004) [Pubmed]
  11. Structural insights into the stereochemistry of the cyclooxygenase reaction. Kiefer, J.R., Pawlitz, J.L., Moreland, K.T., Stegeman, R.A., Hood, W.F., Gierse, J.K., Stevens, A.M., Goodwin, D.C., Rowlinson, S.W., Marnett, L.J., Stallings, W.C., Kurumbail, R.G. Nature (2000) [Pubmed]
  12. Role of cyclooxygenase-2, but not cyclooxygenase-1, on type II collagen-induced arthritis in DBA/1J mice. Ochi, T., Ohkubo, Y., Mutoh, S. Biochem. Pharmacol. (2003) [Pubmed]
  13. A protective role for cyclooxygenase-2 in drug-induced liver injury in mice. Reilly, T.P., Brady, J.N., Marchick, M.R., Bourdi, M., George, J.W., Radonovich, M.F., Pise-Masison, C.A., Pohl, L.R. Chem. Res. Toxicol. (2001) [Pubmed]
  14. The isozyme-specific effects of cyclooxygenase-deficiency on bone in mice. Myers, L.K., Bhattacharya, S.D., Herring, P.A., Xing, Z., Goorha, S., Smith, R.A., Bhattacharya, S.K., Carbone, L., Faccio, R., Kang, A.H., Ballou, L.R. Bone (2006) [Pubmed]
  15. Levels of cyclooxygenase-1 and -2 mRNA expression at various stages of acute gastric injury induced by ischemia-reperfusion in rats. Kishimoto, Y., Wada, K., Nakamoto, K., Kawasaki, H., Hasegawa, J. Arch. Biochem. Biophys. (1998) [Pubmed]
  16. Regulation of macrophage eicosanoid generation is dependent on nuclear factor kappaB. Lo, C.J., Cryer, H.G., Fu, M., Lo, F.R. The Journal of trauma. (1998) [Pubmed]
  17. Malignant transformation and antineoplastic actions of nonsteroidal antiinflammatory drugs (NSAIDs) on cyclooxygenase-null embryo fibroblasts. Zhang, X., Morham, S.G., Langenbach, R., Young, D.A. J. Exp. Med. (1999) [Pubmed]
  18. Cyclooxygenase-1-selective inhibition prolongs gestation in mice without adverse effects on the ductus arteriosus. Loftin, C.D., Trivedi, D.B., Langenbach, R. J. Clin. Invest. (2002) [Pubmed]
  19. Role of immunologic factors and cyclooxygenase 2 in persistent postinfective enteric muscle dysfunction in mice. Barbara, G., De Giorgio, R., Deng, Y., Vallance, B., Blennerhassett, P., Collins, S.M. Gastroenterology (2001) [Pubmed]
  20. Cytokine and cyclooxygenase-2 protein in brain areas of tumor-bearing mice with prostanoid-related anorexia. Wang, W., Lönnroth, C., Svanberg, E., Lundholm, K. Cancer Res. (2001) [Pubmed]
  21. Compensatory prostaglandin E2 biosynthesis in cyclooxygenase 1 or 2 null cells. Kirtikara, K., Morham, S.G., Raghow, R., Laulederkind, S.J., Kanekura, T., Goorha, S., Ballou, L.R. J. Exp. Med. (1998) [Pubmed]
  22. Structural basis for selective inhibition of cyclooxygenase-2 by anti-inflammatory agents. Kurumbail, R.G., Stevens, A.M., Gierse, J.K., McDonald, J.J., Stegeman, R.A., Pak, J.Y., Gildehaus, D., Miyashiro, J.M., Penning, T.D., Seibert, K., Isakson, P.C., Stallings, W.C. Nature (1996) [Pubmed]
  23. Constitutive expression and function of cyclooxygenase-2 in murine gastric muscles. Porcher, C., Horowitz, B., Bayguinov, O., Ward, S.M., Sanders, K.M. Gastroenterology (2002) [Pubmed]
  24. Growth differentiation factor-9 stimulates progesterone synthesis in granulosa cells via a prostaglandin E2/EP2 receptor pathway. Elvin, J.A., Yan, C., Matzuk, M.M. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  25. Inducible isoforms of cyclooxygenase and nitric-oxide synthase in inflammation. Vane, J.R., Mitchell, J.A., Appleton, I., Tomlinson, A., Bishop-Bailey, D., Croxtall, J., Willoughby, D.A. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  26. Transient expression of prostaglandin endoperoxide synthase-2 during mouse macrophage activation. Riese, J., Hoff, T., Nordhoff, A., DeWitt, D.L., Resch, K., Kaever, V. J. Leukoc. Biol. (1994) [Pubmed]
  27. Up-regulation of prostaglandin biosynthesis by leukotriene C4 in elicited mice peritoneal macrophages activated with lipopolysaccharide/interferon-{gamma}. Rossi, A., Acquaviva, A.M., Iuliano, F., Di Paola, R., Cuzzocrea, S., Sautebin, L. J. Leukoc. Biol. (2005) [Pubmed]
  28. Endogenous Prostaglandins E(2) and F(2(alpha)) Serve as an Anti-Apoptotic Factor against Apoptosis Induced by Tumor Necrosis Factor-alpha in Mouse 3T3-L1 Preadipocytes. Nishimura, K., Setoyama, T., Tsumagari, H., Miyata, N., Hatano, Y., Xu, L., Jisaka, M., Nagaya, T., Yokota, K. Biosci. Biotechnol. Biochem. (2006) [Pubmed]
  29. Functional coupling between secretory phospholipase A2 and cyclooxygenase-2 and its regulation by cytosolic group IV phospholipase A2. Balsinde, J., Balboa, M.A., Dennis, E.A. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  30. Nitric oxide synthase/COX cross-talk: nitric oxide activates COX-1 but inhibits COX-2-derived prostaglandin production. Clancy, R., Varenika, B., Huang, W., Ballou, L., Attur, M., Amin, A.R., Abramson, S.B. J. Immunol. (2000) [Pubmed]
  31. Cyclooxygenase-1-dependent prostaglandin synthesis modulates tumor necrosis factor-alpha secretion in lipopolysaccharide-challenged murine resident peritoneal macrophages. Rouzer, C.A., Kingsley, P.J., Wang, H., Zhang, H., Morrow, J.D., Dey, S.K., Marnett, L.J. J. Biol. Chem. (2004) [Pubmed]
  32. Prostaglandin E2 and microsomal prostaglandin E synthase-2 expression are decreased in the cyclooxygenase-2-deficient mouse brain despite compensatory induction of cyclooxygenase-1 and Ca2+-dependent phospholipase A2. Bosetti, F., Langenbach, R., Weerasinghe, G.R. J. Neurochem. (2004) [Pubmed]
  33. Cyclooxygenase-2 inhibitor treatment enhances photodynamic therapy-mediated tumor response. Ferrario, A., Von Tiehl, K., Wong, S., Luna, M., Gomer, C.J. Cancer Res. (2002) [Pubmed]
  34. Is prostaglandin E(2) a pathogenic factor in amyotrophic lateral sclerosis? Almer, G., Kikuchi, H., Teismann, P., Przedborski, S. Ann. Neurol. (2006) [Pubmed]
  35. Transcriptional roles of nuclear factor kappa B and nuclear factor-interleukin-6 in the tumor necrosis factor alpha-dependent induction of cyclooxygenase-2 in MC3T3-E1 cells. Yamamoto, K., Arakawa, T., Ueda, N., Yamamoto, S. J. Biol. Chem. (1995) [Pubmed]
  36. Cyclooxygenase-1 overexpression decreases Basal airway responsiveness but not allergic inflammation. Card, J.W., Carey, M.A., Bradbury, J.A., Graves, J.P., Lih, F.B., Moorman, M.P., Morgan, D.L., Degraff, L.M., Zhao, Y., Foley, J.F., Zeldin, D.C. J. Immunol. (2006) [Pubmed]
  37. Cyclooxygenase 1 is required for pH control at the mouse gastric surface. Baumgartner, H.K., Starodub, O.T., Joehl, J.S., Tackett, L., Montrose, M.H. Gut (2004) [Pubmed]
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