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Gene Review

Ptges  -  prostaglandin E synthase

Mus musculus

Synonyms: 2410099E23Rik, D2Ertd369e, Microsomal prostaglandin E synthase 1, Pges, Prostaglandin E synthase, ...
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Disease relevance of Ptges


Psychiatry related information on Ptges


High impact information on Ptges

  • Our findings identify mPGES-1 as the central switch during immune-induced pyresis and as a target for the treatment of fever and other PGE2-dependent acute phase reactions elicited by the brain [9].
  • We studied the febrile response in mice deficient in microsomal prostaglandin E synthase-1 (mPGES-1), an inducible terminal isomerase expressed in cytokine-sensitive brain endothelial cells [9].
  • Hyperplastic gastric tumors induced by activated macrophages in COX-2/mPGES-1 transgenic mice [3].
  • Stimulation of mPGES-1(-/-) VSMC and macrophages with bacterial LPS increased PGI(2) and thromboxane A(2) to varied extents [10].
  • Urinary PGE-M was depressed, whereas urinary 2,3-dinor 6-keto PGF(1alpha), but not 2,3-dinor-TxB(2), was increased in mPGES-1(-/-) LDLR(-/-)s. mPGES-1-derived PGE(2) accelerates atherogenesis in LDLR(-/-) mice [10].

Chemical compound and disease context of Ptges


Biological context of Ptges

  • Thus, COX-2 and mPGES are essential components for delayed PGE(2) biosynthesis, which may be linked to inflammation, fever, osteogenesis, and even cancer [12].
  • Here we have used mPGES-1 wild type, heterozygote, and null mice to assess the impact of reduction or absence mPGES-1 protein on the production of PGE2 and other prostaglandins in lipopolysaccharide (LPS)-treated macrophages and mice [13].
  • Phase 1 involves transcriptional up-regulation of the couple COX-2 -->mPGES-1 in the liver and lungs [14].
  • The high magnitude of up-regulation of mPGES and sPLA2-IIA (1,260 and 130 fold, respectively) and that of down-regulation of 15-PGES (30 fold) during LPS fever makes these enzymes attractive targets for anti-inflammatory therapy [14].
  • Both mPGES-1 mRNA and protein were only observed in the subluminal stroma surrounding the implanting blastocyst at the implantation site on day 6 of pregancy , but were not seen in the inter-implantation site on day 6 of pregnancy and on day 6 of pseudopregnancy [15].

Anatomical context of Ptges

  • In polyps >1 mm, not only COX-2 but also mPGES was induced in the stromal fibroblasts where COX-1 had already been expressed [1].
  • Thioglycollate-elicited peritoneal macrophages with mPGES-1 deficiency were found to lose their ability to produce PGE2 upon LPS stimulation [13].
  • Other prostaglandins (thromboxane B2, PGD2, PGF(2alpha), and 6-keto-PGF(1alpha)) were significantly elevated in stomachs of mPGES-1-null mice but not in other tissues [13].
  • Cytosolic and microsomal PGE synthases (cPGES and mPGES) were also found, but they occurred diffusely across the cytosol [16].
  • Our data suggest that the presence of an active blastocyst is required for mPGES-1 expression at the implantation site [15].

Associations of Ptges with chemical compounds


Enzymatic interactions of Ptges

  • The membrane fraction containing recombinant mPGES-1 catalyzed the isomerization of PGH2 to PGE2 in the presence of GSH with K(m) values of 130 microM for PGH2 and 37 microM for GSH, a turnover number of 600 min(-1), and a k(cat)/K(m) ratio of 4.6 min(-1) microM(-1) [20].

Regulatory relationships of Ptges


Other interactions of Ptges

  • Examination of mRNA for several terminal prostaglandin synthases did not reveal changes in expression levels associated with mPGES-1 deficiency, indicating that gastric prostaglandin changes may be due to shunting of cyclooxygenase products to other terminal synthases [13].
  • The purpose of this study was to elucidate the regulation of mPGES-1 mRNA expression in cardiomyocytes, define the role of JNK enzymes in this process, and characterize the role of mPGES-1 in cardiomyocyte PGE(2) biosynthesis [25].
  • The tumor tissues were quantified for the induction of apoptosis, intratumor levels/expressions of prostaglandin E2 (PGE2), 15 deoxy prostaglandin J2 (15-d PGJ2), microsomal prostaglandin E synthase (mPGES) and cytoplasmic phospholipase A2 (cPLA2) [26].
  • However, microsomal PGE synthase (mPGES) and lipocalin-type PGD synthase (L-PGDS) were selectively upregulated [27].
  • The expression of mPGES was not induced by LPS in mice lacking Toll-like receptor 4 or MyD88 [28].

Analytical, diagnostic and therapeutic context of Ptges


  1. Cooperation of cyclooxygenase 1 and cyclooxygenase 2 in intestinal polyposis. Takeda, H., Sonoshita, M., Oshima, H., Sugihara, K., Chulada, P.C., Langenbach, R., Oshima, M., Taketo, M.M. Cancer Res. (2003) [Pubmed]
  2. Prostaglandin E synthase in the pathophysiology of arthritis. Kojima, F., Kato, S., Kawai, S. Fundamental & clinical pharmacology. (2005) [Pubmed]
  3. Hyperplastic gastric tumors induced by activated macrophages in COX-2/mPGES-1 transgenic mice. Oshima, H., Oshima, M., Inaba, K., Taketo, M.M. EMBO J. (2004) [Pubmed]
  4. Reduced pain hypersensitivity and inflammation in mice lacking microsomal prostaglandin e synthase-1. Kamei, D., Yamakawa, K., Takegoshi, Y., Mikami-Nakanishi, M., Nakatani, Y., Oh-Ishi, S., Yasui, H., Azuma, Y., Hirasawa, N., Ohuchi, K., Kawaguchi, H., Ishikawa, Y., Ishii, T., Uematsu, S., Akira, S., Murakami, M., Kudo, I. J. Biol. Chem. (2004) [Pubmed]
  5. Cyclooxygenase-2 and microsomal prostaglandin E synthase-1 are overexpressed in squamous cell carcinoma of the penis. Golijanin, D., Tan, J.Y., Kazior, A., Cohen, E.G., Russo, P., Dalbagni, G., Auborn, K.J., Subbaramaiah, K., Dannenberg, A.J. Clin. Cancer Res. (2004) [Pubmed]
  6. Association of microsomal prostaglandin E synthase 1 deficiency with impaired fracture healing, but not with bone loss or osteoarthritis, in mouse models of skeletal disorders. Yamakawa, K., Kamekura, S., Kawamura, N., Saegusa, M., Kamei, D., Murakami, M., Kudo, I., Uematsu, S., Akira, S., Chung, U.I., Nakamura, K., Kawaguchi, H. Arthritis Rheum. (2008) [Pubmed]
  7. Impaired febrile responses to immune challenge in mice deficient in microsomal prostaglandin E synthase-1. Saha, S., Engström, L., Mackerlova, L., Jakobsson, P.J., Blomqvist, A. Am. J. Physiol. Regul. Integr. Comp. Physiol. (2005) [Pubmed]
  8. Involvement of central microsomal prostaglandin E synthase-1 in IL-1beta-induced anorexia. Pecchi, E., Dallaporta, M., Thirion, S., Salvat, C., Berenbaum, F., Jean, A., Troadec, J.D. Physiol. Genomics (2006) [Pubmed]
  9. Microsomal prostaglandin E synthase-1 is the central switch during immune-induced pyresis. Engblom, D., Saha, S., Engström, L., Westman, M., Audoly, L.P., Jakobsson, P.J., Blomqvist, A. Nat. Neurosci. (2003) [Pubmed]
  10. Deletion of microsomal prostaglandin E synthase-1 augments prostacyclin and retards atherogenesis. Wang, M., Zukas, A.M., Hui, Y., Ricciotti, E., Pur??, E., Fitzgerald, G.A. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  11. Change in prostaglandin E synthases (PGESs) in microsomal PGES-1 knockout mice in a preterm delivery model. Kubota, K., Kubota, T., Kamei, D., Murakami, M., Kudo, I., Aso, T., Morita, I. J. Endocrinol. (2005) [Pubmed]
  12. Regulation of prostaglandin E2 biosynthesis by inducible membrane-associated prostaglandin E2 synthase that acts in concert with cyclooxygenase-2. Murakami, M., Naraba, H., Tanioka, T., Semmyo, N., Nakatani, Y., Kojima, F., Ikeda, T., Fueki, M., Ueno, A., Oh, S., Kudo, I. J. Biol. Chem. (2000) [Pubmed]
  13. Deletion of microsomal prostaglandin E2 (PGE2) synthase-1 reduces inducible and basal PGE2 production and alters the gastric prostanoid profile. Boulet, L., Ouellet, M., Bateman, K.P., Ethier, D., Percival, M.D., Riendeau, D., Mancini, J.A., Méthot, N. J. Biol. Chem. (2004) [Pubmed]
  14. Prostaglandin E2 as a mediator of fever: synthesis and catabolism. Ivanov, A.I., Romanovsky, A.A. Front. Biosci. (2004) [Pubmed]
  15. Differential expression and regulation of cylooxygenases, prostaglandin E synthases and prostacyclin synthase in rat uterus during the peri-implantation period. Cong, J., Diao, H.L., Zhao, Y.C., Ni, H., Yan, Y.Q., Yang, Z.M. Reproduction (2006) [Pubmed]
  16. Cyclooxygenase-1 and cyclooxygenase-2 in the mouse ductus arteriosus: individual activity and functional coupling with nitric oxide synthase. Baragatti, B., Brizzi, F., Ackerley, C., Barogi, S., Ballou, L.R., Coceani, F. Br. J. Pharmacol. (2003) [Pubmed]
  17. Role of cytosolic phospholipase A(2) in prostaglandin E(2) production by lung fibroblasts. Ghosh, M., Stewart, A., Tucker, D.E., Bonventre, J.V., Murphy, R.C., Leslie, C.C. Am. J. Respir. Cell Mol. Biol. (2004) [Pubmed]
  18. Cyclooxygenases and prostaglandin E synthases in the endometrium of the rhesus monkey during the menstrual cycle. Sun, T., Li, S.J., Diao, H.L., Teng, C.B., Wang, H.B., Yang, Z.M. Reproduction (2004) [Pubmed]
  19. Inhibition of prostaglandin E2 synthesis by SC-560 is independent of cyclooxygenase 1 inhibition. Brenneis, C., Maier, T.J., Schmidt, R., Hofacker, A., Zulauf, L., Jakobsson, P.J., Scholich, K., Geisslinger, G. FASEB J. (2006) [Pubmed]
  20. Biochemical characterization of mouse microsomal prostaglandin E synthase-1 and its colocalization with cyclooxygenase-2 in peritoneal macrophages. Lazarus, M., Kubata, B.K., Eguchi, N., Fujitani, Y., Urade, Y., Hayaishi, O. Arch. Biochem. Biophys. (2002) [Pubmed]
  21. Transcriptional regulation of the membrane-associated prostaglandin E2 synthase gene. Essential role of the transcription factor Egr-1. Naraba, H., Yokoyama, C., Tago, N., Murakami, M., Kudo, I., Fueki, M., Oh-Ishi, S., Tanabe, T. J. Biol. Chem. (2002) [Pubmed]
  22. Microglia-specific expression of microsomal prostaglandin E2 synthase-1 contributes to lipopolysaccharide-induced prostaglandin E2 production. Ikeda-Matsuo, Y., Ikegaya, Y., Matsuki, N., Uematsu, S., Akira, S., Sasaki, Y. J. Neurochem. (2005) [Pubmed]
  23. mPGES-1 as a novel target for arthritis. Fahmi, H. Current opinion in rheumatology. (2004) [Pubmed]
  24. Urogenital distribution of a mouse membrane-associated prostaglandin E(2) synthase. Guan, Y., Zhang, Y., Schneider, A., Riendeau, D., Mancini, J.A., Davis, L., Kömhoff, M., Breyer, R.M., Breyer, M.D. Am. J. Physiol. Renal Physiol. (2001) [Pubmed]
  25. c-Jun N-terminal kinase-mediated stabilization of microsomal prostaglandin E2 synthase-1 mRNA regulates delayed microsomal prostaglandin E2 synthase-1 expression and prostaglandin E2 biosynthesis by cardiomyocytes. Degousee, N., Angoulvant, D., Fazel, S., Stefanski, E., Saha, S., Iliescu, K., Lindsay, T.F., Fish, J.E., Marsden, P.A., Li, R.K., Audoly, L.P., Jakobsson, P.J., Rubin, B.B. J. Biol. Chem. (2006) [Pubmed]
  26. Enhancement of antitumor activity of docetaxel by celecoxib in lung tumors. Shaik, M.S., Chatterjee, A., Jackson, T., Singh, M. Int. J. Cancer (2006) [Pubmed]
  27. Differentiation-dependent regulation of the cyclooxygenase cascade during adipogenesis suggests a complex role for prostaglandins. Xie, Y., Kang, X., Ackerman, W.E., Belury, M.A., Koster, C., Rovin, B.H., Landon, M.B., Kniss, D.A. Diabetes, obesity & metabolism. (2006) [Pubmed]
  28. Lipopolysaccharide-dependent prostaglandin E(2) production is regulated by the glutathione-dependent prostaglandin E(2) synthase gene induced by the Toll-like receptor 4/MyD88/NF-IL6 pathway. Uematsu, S., Matsumoto, M., Takeda, K., Akira, S. J. Immunol. (2002) [Pubmed]
  29. Membrane-associated PGE synthase-1 (mPGES-1) is coexpressed with both COX-1 and COX-2 in the kidney. Schneider, A., Zhang, Y., Zhang, M., Lu, W.J., Rao, R., Fan, X., Redha, R., Davis, L., Breyer, R.M., Harris, R., Guan, Y., Breyer, M.D. Kidney Int. (2004) [Pubmed]
  30. Immunohistochemical localization of microsomal PGE synthase-1 and cyclooxygenases in male mouse reproductive organs. Lazarus, M., Munday, C.J., Eguchi, N., Matsumoto, S., Killian, G.J., Kubata, B.K., Urade, Y. Endocrinology (2002) [Pubmed]
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