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Gene Review

Ptgs2  -  prostaglandin-endoperoxide synthase 2

Rattus norvegicus

Synonyms: COX-2, Cox-2, Cox2, Cyclooxygenase-2, PGH synthase 2, ...
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Disease relevance of Ptgs2


Psychiatry related information on Ptgs2


High impact information on Ptgs2


Chemical compound and disease context of Ptgs2


Biological context of Ptgs2

  • PG production was associated with upregulation of COX-2 mRNA and protein in the affected paws [1].
  • The intrarenal distribution of COX-2 and its increased expression in response to sodium restriction suggest that in addition to its proposed role in inflammatory and growth responses, this enzyme may play an important role in the regulation of salt, volume, and blood pressure homeostasis [18].
  • Immunoblotting and immunohistochemistry were performed to evaluate the effects of duodenal reflux on COX-2 expression and cell proliferation in esophageal tissue [3].
  • Pathological analyses and measurements of lipid peroxidation, tumor necrosis factor (TNF)-alpha, COX-1 and COX-2 messenger RNA (mRNA), endotoxin, and liver and plasma thromboxane were performed [4].
  • RESULTS: Administration of SC-236 to cirrhotic animals did not produce significant renal effects, whereas administration of the nonselective COX-1/COX-2 inhibitor, ketorolac, resulted in a marked reduction in urine volume, urinary excretion of prostaglandins, and glomerular filtration rate and in a significant impairment in renal water metabolism [2].

Anatomical context of Ptgs2


Associations of Ptgs2 with chemical compounds

  • Immunoreactive COX-2 was increased in D rats compared with C rats and normalized by improved glycemic control [19].
  • Indomethacin, but not a highly selective COX-2 inhibitor or an inducible NOS inhibitor, abolished long-term endotoxin-induced gastric resistance to injury [20].
  • RESULTS: Unconjugated bile acids were about fivefold more potent inducers of COX-2 messenger RNA, COX-2 protein, and prostaglandin synthesis than conjugated bile acids [3].
  • The results of this study provide evidence, for the first time, that a specific COX-2 inhibitor, celecoxib, possesses strong chemopreventive activity against colon carcinogenesis [21].
  • HFCO further enhanced the AOM-induced COX-2 expression [22].

Physical interactions of Ptgs2

  • Treatment with a p38 MAPK inhibitor, PD169316, or transfection with a dominant-negative p38 MAPK construct reversed the effect of CD or ceramide to stabilize COX-2 mRNA [23].
  • The distribution of cyclooxygenase-2 and membrane bound prostaglandin E synthase messenger RNA expressing cells suggests major involvement of non-neuronal cells in spinal prostaglandin biosynthesis [24].
  • The results suggest that the anti-inflammatory properties of oxyresveratrol might be correlated with inhibition of the iNOS expression through down-regulation of NF-kappaB binding activity and significant inhibition of COX-2 activity [25].
  • A docking experiment to determine the orientation of (Z)-9c within the COX-2 binding site showed that the linear p-N3 group inserts into the COX-2 2 degrees-pocket, where it undergoes an ion-ion (electrostatic) interaction with Arg513 [26].

Regulatory relationships of Ptgs2


Other interactions of Ptgs2

  • In conclusion, we documented an increase in renal cortical COX-2 protein expression associated with a different renal hemodynamic response to selective systemic COX-2 inhibition in D as compared with C animals, indicating a role of COX-2-derived PG in pathological renal hemodynamic changes in diabetes [19].
  • Elevated levels of cyclooxygenase-2 in antigen-stimulated mast cells is associated with minimal activation of p38 mitogen-activated protein kinase [33].
  • Cytosolic phospholipase A2 is required for cytokine-induced expression of type IIA secretory phospholipase A2 that mediates optimal cyclooxygenase-2-dependent delayed prostaglandin E2 generation in rat 3Y1 fibroblasts [34].
  • Studies using an anti-type IIA sPLA2 antibody, sPLA2 inhibitors, and a type IIA sPLA2-specific antisense oligonucleotide revealed that IL-1 beta/TNF alpha-induced delayed PGE2 generation by these cells was largely dependent on inducible type IIA sPLA2, which was functionally linked to inducible COX-2 [34].
  • ET-1 induction of PGHS-2 protein was accompanied by a sustained enhancement of enzymatic activity assessed by conversion of arachidonic acid to prostaglandin E2 [27].

Analytical, diagnostic and therapeutic context of Ptgs2


  1. Selective inhibition of cyclooxygenase (COX)-2 reverses inflammation and expression of COX-2 and interleukin 6 in rat adjuvant arthritis. Anderson, G.D., Hauser, S.D., McGarity, K.L., Bremer, M.E., Isakson, P.C., Gregory, S.A. J. Clin. Invest. (1996) [Pubmed]
  2. Selective inhibition of cyclooxygenase 2 spares renal function and prostaglandin synthesis in cirrhotic rats with ascites. Bosch-Marcè, M., Clària, J., Titos, E., Masferrer, J.L., Altuna, R., Poo, J.L., Jiménez, W., Arroyo, V., Rivera, F., Rodés, J. Gastroenterology (1999) [Pubmed]
  3. Duodenal reflux induces cyclooxygenase-2 in the esophageal mucosa of rats: evidence for involvement of bile acids. Zhang, F., Altorki, N.K., Wu, Y.C., Soslow, R.A., Subbaramaiah, K., Dannenberg, A.J. Gastroenterology (2001) [Pubmed]
  4. Enhanced cyclooxygenase-2 gene expression in alcoholic liver disease in the rat. Nanji, A.A., Miao, L., Thomas, P., Rahemtulla, A., Khwaja, S., Zhao, S., Peters, D., Tahan, S.R., Dannenberg, A.J. Gastroenterology (1997) [Pubmed]
  5. Induction of cyclooxygenase-2 and peroxisome proliferator-activated receptor-gamma during nitric oxide-induced apoptotic PC12 cell death. Lim, S.Y., Jang, J.H., Surh, Y.J. Ann. N. Y. Acad. Sci. (2003) [Pubmed]
  6. Intrathecal administration of a cylcooxygenase-1, but not a cyclooxygenase-2 inhibitor, reverses the effects of laparotomy on exploratory activity in rats. Martin, T.J., Buechler, N.L., Eisenach, J.C. Anesth. Analg. (2006) [Pubmed]
  7. Valproic acid down-regulates the conversion of arachidonic acid to eicosanoids via cyclooxygenase-1 and -2 in rat brain. Bosetti, F., Weerasinghe, G.R., Rosenberger, T.A., Rapoport, S.I. J. Neurochem. (2003) [Pubmed]
  8. Enhancement of slow-wave sleep by tumor necrosis factor-alpha is mediated by cyclooxygenase-2 in rats. Terao, A., Matsumura, H., Yoneda, H., Saito, M. Neuroreport (1998) [Pubmed]
  9. COX-2, a synaptically induced enzyme, is expressed by excitatory neurons at postsynaptic sites in rat cerebral cortex. Kaufmann, W.E., Worley, P.F., Pegg, J., Bremer, M., Isakson, P. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  10. Alterations in cellular adhesion and apoptosis in epithelial cells overexpressing prostaglandin endoperoxide synthase 2. Tsujii, M., DuBois, R.N. Cell (1995) [Pubmed]
  11. Inducible cyclooxygenase may have anti-inflammatory properties. Gilroy, D.W., Colville-Nash, P.R., Willis, D., Chivers, J., Paul-Clark, M.J., Willoughby, D.A. Nat. Med. (1999) [Pubmed]
  12. Inhibition of cyclooxygenase-2 potentiates retrograde endocannabinoid effects in hippocampus. Kim, J., Alger, B.E. Nat. Neurosci. (2004) [Pubmed]
  13. Rat pulmonary cyclooxygenase-2 expression in response to endotoxin challenge: differential regulation in the various types of cells in the lung. Ermert, L., Ermert, M., Merkle, M., Goppelt-Struebe, M., Duncker, H.R., Grimminger, F., Seeger, W. Am. J. Pathol. (2000) [Pubmed]
  14. Losartan modulation on NOS isoforms and COX-2 expression in early renal fibrogenesis in unilateral obstruction. Manucha, W., Oliveros, L., Carrizo, L., Seltzer, A., Vallés, P. Kidney Int. (2004) [Pubmed]
  15. Effect of flosulide, a selective cyclooxygenase 2 inhibitor, on passive heymann nephritis in the rat. Blume, C., Heise, G., Mühlfeld, A., Bach, D., Schrör, K., Gerhardz, C.D., Grabensee, B., Heering, P. Kidney Int. (1999) [Pubmed]
  16. Effects of inhibition of prostaglandin endoperoxide synthase-2 in chronic gastro-intestinal ulcer models in rats. Schmassmann, A., Peskar, B.M., Stettler, C., Netzer, P., Stroff, T., Flogerzi, B., Halter, F. Br. J. Pharmacol. (1998) [Pubmed]
  17. Enhanced cyclooxygenase-2 expression in olfactory-limbic forebrain following kainate-induced seizures. Joseph, S.A., Lynd-Balta, E., O'Banion, M.K., Rappold, P.M., Daschner, J., Allen, A., Padowski, J. Neuroscience (2006) [Pubmed]
  18. Cyclooxygenase-2 is associated with the macula densa of rat kidney and increases with salt restriction. Harris, R.C., McKanna, J.A., Akai, Y., Jacobson, H.R., Dubois, R.N., Breyer, M.D. J. Clin. Invest. (1994) [Pubmed]
  19. Immunohistochemical and functional correlations of renal cyclooxygenase-2 in experimental diabetes. Komers, R., Lindsley, J.N., Oyama, T.T., Schutzer, W.E., Reed, J.F., Mader, S.L., Anderson, S. J. Clin. Invest. (2001) [Pubmed]
  20. Induction of cyclooxygenase 1 and 2 in the rat stomach during endotoxemia: role in resistance to damage. Ferraz, J.G., Sharkey, K.A., Reuter, B.K., Asfaha, S., Tigley, A.W., Brown, M.L., McKnight, W., Wallace, J.L. Gastroenterology (1997) [Pubmed]
  21. Chemopreventive activity of celecoxib, a specific cyclooxygenase-2 inhibitor, against colon carcinogenesis. Kawamori, T., Rao, C.V., Seibert, K., Reddy, B.S. Cancer Res. (1998) [Pubmed]
  22. Dietary fat and colon cancer: modulation of cyclooxygenase-2 by types and amount of dietary fat during the postinitiation stage of colon carcinogenesis. Singh, J., Hamid, R., Reddy, B.S. Cancer Res. (1997) [Pubmed]
  23. Posttranscriptional regulation of cyclooxygenase-2 in rat intestinal epithelial cells. Zhang, Z., Sheng, H., Shao, J., Beauchamp, R.D., DuBois, R.N. Neoplasia (2000) [Pubmed]
  24. Effect of endotoxin treatment on the expression of cyclooxygenase-2 and prostaglandin synthases in spinal cord, dorsal root ganglia, and skin of rats. Schuligoi, R., Ulcar, R., Peskar, B.A., Amann, R. Neuroscience (2003) [Pubmed]
  25. In-vitro and in-vivo anti-inflammatory effect of oxyresveratrol from Morus alba L. Chung, K.O., Kim, B.Y., Lee, M.H., Kim, Y.R., Chung, H.Y., Park, J.H., Moon, J.O. J. Pharm. Pharmacol. (2003) [Pubmed]
  26. Design and synthesis of (Z)-1,2-diphenyl-1-(4-methanesulfonamidophenyl)alk-1-enes and (Z)-1-(4-azidophenyl)-1,2-diphenylalk-1-enes: novel inhibitors of cyclooxygenase-2 (COX-2) with anti-inflammatory and analgesic activity. Uddin, M.J., Praveen Rao, P.N., Knaus, E.E. Bioorg. Med. Chem. (2005) [Pubmed]
  27. Endothelin stimulates prostaglandin endoperoxide synthase-2 mRNA expression and protein synthesis through a tyrosine kinase-signaling pathway in rat mesangial cells. Kester, M., Coroneos, E., Thomas, P.J., Dunn, M.J. J. Biol. Chem. (1994) [Pubmed]
  28. Gastrin stimulates cyclooxygenase-2 expression in intestinal epithelial cells through multiple signaling pathways. Evidence for involvement of ERK5 kinase and transactivation of the epidermal growth factor receptor. Guo, Y.S., Cheng, J.Z., Jin, G.F., Gutkind, J.S., Hellmich, M.R., Townsend, C.M. J. Biol. Chem. (2002) [Pubmed]
  29. Interleukin-13 enhances cyclooxygenase-2 expression in activated rat brain microglia: implications for death of activated microglia. Yang, M.S., Ji, K.A., Jeon, S.B., Jin, B.K., Kim, S.U., Jou, I., Joe, E. J. Immunol. (2006) [Pubmed]
  30. Activation of the epidermal growth factor receptor in optic nerve astrocytes leads to early and transient induction of cyclooxygenase-2. Zhang, X., Neufeld, A.H. Invest. Ophthalmol. Vis. Sci. (2005) [Pubmed]
  31. Up-regulation of cyclooxygenase-2 by inhibition of cyclooxygenase-1: a key to nonsteroidal anti-inflammatory drug-induced intestinal damage. Tanaka, A., Hase, S., Miyazawa, T., Takeuchi, K. J. Pharmacol. Exp. Ther. (2002) [Pubmed]
  32. Platelet-derived growth factor-induced stabilization of cyclooxygenase 2 mRNA in rat smooth muscle cells requires the c-Src family of protein-tyrosine kinases. Xu, K., Kitchen, C.M., Shu, H.K., Murphy, T.J. J. Biol. Chem. (2007) [Pubmed]
  33. Elevated levels of cyclooxygenase-2 in antigen-stimulated mast cells is associated with minimal activation of p38 mitogen-activated protein kinase. Hundley, T.R., Prasad, A.R., Beaven, M.A. J. Immunol. (2001) [Pubmed]
  34. Cytosolic phospholipase A2 is required for cytokine-induced expression of type IIA secretory phospholipase A2 that mediates optimal cyclooxygenase-2-dependent delayed prostaglandin E2 generation in rat 3Y1 fibroblasts. Kuwata, H., Nakatani, Y., Murakami, M., Kudo, I. J. Biol. Chem. (1998) [Pubmed]
  35. Regulation of the expression of cyclooxygenase-2 by nitric oxide in rat peritoneal macrophages. Habib, A., Bernard, C., Lebret, M., Creminon, C., Esposito, B., Tedgui, A., Maclouf, J. J. Immunol. (1997) [Pubmed]
  36. Cyclooxygenase-2-mediated DNA damage. Lee, S.H., Williams, M.V., Dubois, R.N., Blair, I.A. J. Biol. Chem. (2005) [Pubmed]
  37. Regulation of MDR-1 (P-glycoprotein) by cyclooxygenase-2. Patel, V.A., Dunn, M.J., Sorokin, A. J. Biol. Chem. (2002) [Pubmed]
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