Microsomal prostaglandin E synthase-1 (mPGES-1)[1][2] or Prostaglandin E synthase is an enzyme that in humans is encoded by the PTGES gene.[3][4][5]

The protein encoded by this gene is a glutathione-dependent prostaglandin E synthase. The expression of this gene has been shown to be induced by proinflammatory cytokine interleukin 1 beta (IL1B). Its expression can also be induced by tumor suppressor protein TP53, and may be involved in TP53-induced apoptosis.

Knockout studies in mice suggest that this gene may contribute to the pathogenesis of collagen-induced arthritis and mediate acute pain during inflammatory responses.[5]

It is inhibited by crisdesalazine (AAD-2004; GedaCure).[6]

See also

References

  1. ^ Jakobsson PJ, Thorén S, Morgenstern R, et al. (1989). "Identification of human prostaglandin E synthase: a microsomal glutathione-dependent, inducible enzyme, constituting a potential novel drug target.". Proc Natl Acad Sci USA. 96 (13): 7220–7225. Bibcode:1999PNAS...96.7220J. doi:10.1073/pnas.96.13.7220. PMC 22058. PMID 10377395
  2. ^ Hui-Hua Chang & Emmanuelle J Meuillet (2011). "Identification and development of mPGES-1 inhibitors: where we are at?". Future Med Chem. 3 (15): 1909–1934. doi:10.4155/fmc.11.136. PMC 3232027. PMID 22023034
  3. ^ Polyak K, Xia Y, Zweier JL, Kinzler KW, Vogelstein B (Sep 1997). "A model for p53-induced apoptosis". Nature. 389 (6648): 300–5. Bibcode:1997Natur.389..300P. doi:10.1038/38525. PMID 9305847. S2CID 4429638
  4. ^ Jakobsson PJ, Morgenstern R, Mancini J, Ford-Hutchinson A, Persson B (May 1999). "Common structural features of MAPEG -- a widespread superfamily of membrane-associated proteins with highly divergent functions in eicosanoid and glutathione metabolism". Protein Sci. 8 (3): 689–92. doi:10.1110/ps.8.3.689. PMC 2144274. PMID 10091672
  5. ^ "Entrez Gene: PTGES prostaglandin E synthase"
  6. ^ Dunkel P, Chai CL, Sperlágh B, Huleatt PB, Mátyus P (September 2012). "Clinical utility of neuroprotective agents in neurodegenerative diseases: current status of drug development for Alzheimer's, Parkinson's and Huntington's diseases, and amyotrophic lateral sclerosis". Expert Opin Investig Drugs. 21 (9): 1267–308. doi:10.1517/13543784.2012.703178. PMID 22741814

Further reading

  • Bastien L; Sawyer N; Grygorczyk R et al. (1994). "Cloning, functional expression, and characterization of the human prostaglandin E2 receptor EP2 subtype". J. Biol. Chem.. 269 (16): 11873–7. doi:10.1016/S0021-9258(17)32654-6. PMID 8163486
  • Wu T, Wu H, Wang J, Wang J (2011). "Expression and cellular localization of cyclooxygenases and prostaglandin E synthases in the hemorrhagic brain.". J Neuroinflammation. 8: 22. doi:10.1186/1742-2094-8-22. PMC 3062590. PMID 21385433
  • Funk CD; Furci L; FitzGerald GA et al. (1994). "Cloning and expression of a cDNA for the human prostaglandin E receptor EP1 subtype". J. Biol. Chem.. 268 (35): 26767–72. doi:10.1016/S0021-9258(19)74379-8. PMID 8253813
  • Giacomini E; Giordani L; di Modugno F et al. (1998). "Increased PGE2 production mediates the in vitro inhibitory effect of the human immunodeficiency virus P24 immunosuppressive heptapeptide Ch7". Scand. J. Immunol.. 48 (3): 248–53. doi:10.1046/j.1365-3083.1998.00389.x. PMID 9743208. S2CID 20332912
  • Jakobsson PJ, Thorén S, Morgenstern R, Samuelsson B (1999). "Identification of human prostaglandin E synthase: a microsomal, glutathione-dependent, inducible enzyme, constituting a potential novel drug target". Proc. Natl. Acad. Sci. U.S.A.. 96 (13): 7220–5. Bibcode:1999PNAS...96.7220J. doi:10.1073/pnas.96.13.7220. PMC 22058. PMID 10377395
  • Forsberg L; Leeb L; Thorén S et al. (2000). "Human glutathione dependent prostaglandin E synthase: gene structure and regulation". FEBS Lett.. 471 (1): 78–82. doi:10.1016/S0014-5793(00)01367-3. PMID 10760517. S2CID 10901322
  • Han R, Smith TJ (2002). "Cytoplasmic prostaglandin E2 synthase is dominantly expressed in cultured KAT-50 thyrocytes, cells that express constitutive prostaglandin-endoperoxide H synthase-2. Basis for low protaglandin E2 production". J. Biol. Chem.. 277 (39): 36897–903. doi:10.1074/jbc.M206949200. PMID 12145315
  • Giannoulias D; Alfaidy N; Holloway AC et al. (2002). "Expression of prostaglandin I(2) synthase, but not prostaglandin E synthase, changes in myometrium of women at term pregnancy". J. Clin. Endocrinol. Metab.. 87 (11): 5274–82. doi:10.1210/jc.2002-020521. PMID 12414902
  • Ouellet M; Falgueyret JP; Ear PH et al. (2003). "Purification and characterization of recombinant microsomal prostaglandin E synthase-1". Protein Expr. Purif.. 26 (3): 489–95. doi:10.1016/S1046-5928(02)00566-1. PMID 12460774
  • Strausberg RL; Feingold EA; Grouse LH et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A.. 99 (26): 16899–903. Bibcode:2002PNAS...9916899M. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932
  • Uracz W, Uracz D, Olszanecki R, Gryglewski RJ (2003). "Interleukin 1beta induces functional prostaglandin E synthase in cultured human umbilical vein endothelial cells". J. Physiol. Pharmacol.. 53 (4 Pt 1): 643–54. PMID 12512699
  • Meadows JW, Eis AL, Brockman DE, Myatt L (2003). "Expression and localization of prostaglandin E synthase isoforms in human fetal membranes in term and preterm labor". J. Clin. Endocrinol. Metab.. 88 (1): 433–9. doi:10.1210/jc.2002-021061. PMID 12519887
  • Kamei D; Murakami M; Nakatani Y et al. (2003). "Potential role of microsomal prostaglandin E synthase-1 in tumorigenesis". J. Biol. Chem.. 278 (21): 19396–405. doi:10.1074/jbc.M213290200. PMID 12626523
  • Jakobsson PJ, Thorén S, Morgenstern R, Samuelsson B (2003). "Characterization of Microsomal, Glutathione Dependent Prostaglandin e Synthase". Eicosanoids and Other Bioactive Lipids in Cancer, Inflammation, and Radiation Injury, 5. Vol. 507. Advances in Experimental Medicine and Biology. pp. 287–91. doi:10.1007/978-1-4615-0193-0_44. ISBN 978-0-306-47283-1. PMID 12664599
  • Thorén S; Weinander R; Saha S et al. (2003). "Human microsomal prostaglandin E synthase-1: purification, functional characterization, and projection structure determination". J. Biol. Chem.. 278 (25): 22199–209. doi:10.1074/jbc.M303227200. PMID 12672824
  • Alfaidy N, Sun M, Challis JR, Gibb W (2003). "Expression of membrane prostaglandin E synthase in human placenta and fetal membranes and effect of labor". Endocrine. 20 (3): 219–25. doi:10.1385/ENDO:20:3:219. PMID 12721500. S2CID 9590845
  • Ekström L; Lyrenäs L; Jakobsson PJ et al. (2003). "Basal expression of the human MAPEG members microsomal glutathione transferase 1 and prostaglandin E synthase genes is mediated by Sp1 and Sp3". Biochim. Biophys. Acta. 1627 (2–3): 79–84. doi:10.1016/S0167-4781(03)00077-0. PMID 12818425
  • Murakami M; Nakashima K; Kamei D et al. (2003). "Cellular prostaglandin E2 production by membrane-bound prostaglandin E synthase-2 via both cyclooxygenases-1 and -2". J. Biol. Chem.. 278 (39): 37937–47. doi:10.1074/jbc.M305108200. PMID 12835322
  • Trebino CE; Stock JL; Gibbons CP et al. (2003). "Impaired inflammatory and pain responses in mice lacking an inducible prostaglandin E synthase". Proc. Natl. Acad. Sci. U.S.A.. 100 (15): 9044–9. Bibcode:2003PNAS..100.9044T. doi:10.1073/pnas.1332766100. PMC 166435. PMID 12835414