PTGES2
Prostaglandin E synthase 2 is an enzyme that in humans is encoded by the PTGES2 gene.[1][2]
The protein encoded by this gene is a membrane-associated prostaglandin E synthase, which catalyzes the conversion of prostaglandin H2 to prostaglandin E2. This protein also has been shown to activate the transcription regulated by an interferon-gamma gamma-interferon-activated transcription element (GATE).[2]
Model organisms
| Characteristic | Phenotype |
|---|---|
| Homozygote viability | Normal |
| Fertility | Normal |
| Body weight | Normal |
| Anxiety | Normal |
| Neurological assessment | Normal |
| Grip strength | Normal |
| Hot plate | Normal |
| Dysmorphology | Normal |
| Indirect calorimetry | Normal |
| Glucose tolerance test | Normal |
| Auditory brainstem response | Normal |
| DEXA | Normal |
| Radiography | Normal |
| Body temperature | Normal |
| Eye morphology | Normal |
| Clinical chemistry | Normal |
| Haematology | Normal |
| Peripheral blood lymphocytes | Normal |
| Micronucleus test | Normal |
| Heart weight | Normal |
| Salmonella infection | Normal[3] |
| Citrobacter infection | Normal[4] |
| All tests and analysis from[5][6] |
Model organisms have been used in the study of PTGES2 function. A conditional knockout mouse line, called Ptges2tm1a(EUCOMM)Wtsi[7][8] was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists — at the Wellcome Trust Sanger Institute.[9][10][11]
Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[5][12] Twenty two tests were carried out on mutant mice, but no significant abnormalities were observed.[5]
Clinical significance
The excess production of prostaglandin E 2 is known to contribute to inflammatory diseases which includes rheumatoid arthritis, atherosclerosis, and cancer.[13][14] As such, pharmacological inhibition of prostaglandin E 2 production by synthetic minor prenylated chalcones and flavonoids has potential therapeutic viability.[13] It has been shown that the synthesis of prostaglandin E 2 in the endothelial cells of the brain is important for inflammation-induced fever.[15] Additionally, investigators have observed elevations in cell doubling rates for several cancer cell types in the presence of prostaglandin E 2 –producing cell lines.[16]
References
- ↑ Tanikawa N, Ohmiya Y, Ohkubo H, Hashimoto K, Kangawa K, Kojima M, Ito S, Watanabe K (March 2002). "Identification and characterization of a novel type of membrane-associated prostaglandin E synthase". Biochem. Biophys. Res. Commun. 291 (4): 884–9. doi:10.1006/bbrc.2002.6531. PMID 11866447.
- ↑ 2.0 2.1 "Entrez Gene: prostaglandin E synthase 2".
- ↑ "Salmonella infection data for Ptges2". Wellcome Trust Sanger Institute.
- ↑ "Citrobacter infection data for Ptges2". Wellcome Trust Sanger Institute.
- ↑ 5.0 5.1 5.2 Gerdin AK (2010). "The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice". Acta Ophthalmologica 88 (S248). doi:10.1111/j.1755-3768.2010.4142.x.
- ↑ Mouse Resources Portal, Wellcome Trust Sanger Institute.
- ↑ "International Knockout Mouse Consortium".
- ↑ "Mouse Genome Informatics".
- ↑ Skarnes, W. C.; Rosen, B.; West, A. P.; Koutsourakis, M.; Bushell, W.; Iyer, V.; Mujica, A. O.; Thomas, M.; Harrow, J.; Cox, T.; Jackson, D.; Severin, J.; Biggs, P.; Fu, J.; Nefedov, M.; De Jong, P. J.; Stewart, A. F.; Bradley, A. (2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature 474 (7351): 337–342. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.
- ↑ Dolgin E (June 2011). "Mouse library set to be knockout". Nature 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
- ↑ Collins FS, Rossant J, Wurst W (January 2007). "A mouse for all reasons". Cell 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247.
- ↑ van der Weyden L, White JK, Adams DJ, Logan DW (2011). "The mouse genetics toolkit: revealing function and mechanism.". Genome Biol 12 (6): 224. doi:10.1186/gb-2011-12-6-224. PMC 3218837. PMID 21722353.
- ↑ 13.0 13.1 Rullah, K; Mohd Aluwi, M. F.; Yamin, B. M.; Abdul Bahari, M. N.; Wei, L. S.; Ahmad, S; Abas, F; Ismail, N. H.; Jantan, I; Wai, L. K. (2014). "Inhibition of prostaglandin E(2) production by synthetic minor prenylated chalcones and flavonoids: Synthesis, biological activity, crystal structure, and in silico evaluation". Bioorganic & Medicinal Chemistry Letters 24 (16): 3826–34. doi:10.1016/j.bmcl.2014.06.061. PMID 25027933.
- ↑ Jongthawin, J; Chusorn, P; Techasen, A; Loilome, W; Boonmars, T; Thanan, R; Puapairoj, A; Khuntikeo, N; Tassaneeyakul, W; Yongvanit, P; Namwat, N (2014). "PGE2 signaling and its biosynthesis-related enzymes in cholangiocarcinoma progression". Tumor Biology 35 (8): 8051–64. doi:10.1007/s13277-014-2021-y. PMID 24839005.
- ↑ Wilhelms, D. B.; Kirilov, M; Mirrasekhian, E; Eskilsson, A; Kugelberg, U. O.; Klar, C; Ridder, D. A.; Herschman, H. R.; Schwaninger, M; Blomqvist, A; Engblom, D (2014). "Deletion of prostaglandin E2 synthesizing enzymes in brain endothelial cells attenuates inflammatory fever". Journal of Neuroscience 34 (35): 11684–90. doi:10.1523/JNEUROSCI.1838-14.2014. PMID 25164664.
- ↑ Ruan, D; So, S. P. (2014). "Prostaglandin E2 produced by inducible COX-2 and mPGES-1 promoting cancer cell proliferation in vitro and in vivo". Life Sciences 116 (1): 43–50. doi:10.1016/j.lfs.2014.07.042. PMID 25139833.
Further reading
- Lehner B, Sanderson CM (2004). "A protein interaction framework for human mRNA degradation.". Genome Res. 14 (7): 1315–23. doi:10.1101/gr.2122004. PMC 442147. PMID 15231747.
- Palmieri RT, Wilson MA, Iversen ES et al. (2008). "Polymorphism in the IL18 gene and epithelial ovarian cancer in non-Hispanic white women.". Cancer Epidemiol. Biomarkers Prev. 17 (12): 3567–72. doi:10.1158/1055-9965.EPI-08-0548. PMC 2664299. PMID 19064572.
- Chaudhry UA, Dore S (2009). "Cytosolic prostaglandin E synthase: expression patterns in control and Alzheimer's disease brains.". Am J Alzheimers Dis Other Demen 24 (1): 46–51. doi:10.1177/1533317508323655. PMC 2859688. PMID 19001348.
- Dagle JM, Lepp NT, Cooper ME et al. (2009). "Determination of genetic predisposition to patent ductus arteriosus in preterm infants.". Pediatrics 123 (4): 1116–23. doi:10.1542/peds.2008-0313. PMC 2734952. PMID 19336370.
- Fischer A, Grallert H, Böhme M et al. (2009). "Association analysis between the prostaglandin E synthase 2 R298H polymorphism and body mass index in 8079 participants of the KORA study cohort.". Genet Test Mol Biomarkers 13 (2): 223–6. doi:10.1089/gtmb.2008.0111. PMID 19371221.
- Mattila S, Tuominen H, Koivukangas J, Stenbäck F (2009). "The terminal prostaglandin synthases mPGES-1, mPGES-2, and cPGES are all overexpressed in human gliomas.". Neuropathology 29 (2): 156–65. doi:10.1111/j.1440-1789.2008.00963.x. PMID 19347995.
- Humphray SJ, Oliver K, Hunt AR et al. (2004). "DNA sequence and analysis of human chromosome 9.". Nature 429 (6990): 369–74. doi:10.1038/nature02465. PMC 2734081. PMID 15164053.
- Lindner I, Helwig U, Rubin D et al. (2007). "Prostaglandin E synthase 2 (PTGES2) Arg298His polymorphism and parameters of the metabolic syndrome.". Mol Nutr Food Res 51 (12): 1447–51. doi:10.1002/mnfr.200700144. PMID 17979097.
- Seo T, Tatsuguchi A, Shinji S et al. (2009). "Microsomal prostaglandin E synthase protein levels correlate with prognosis in colorectal cancer patients.". Virchows Arch. 454 (6): 667–76. doi:10.1007/s00428-009-0777-z. PMID 19412621.
- Lee E, Choi MK, Lee YJ et al. (2006). "Alpha-tocopheryl succinate, in contrast to alpha-tocopherol and alpha-tocopheryl acetate, inhibits prostaglandin E2 production in human lung epithelial cells.". Carcinogenesis 27 (11): 2308–15. doi:10.1093/carcin/bgl073. PMID 16714329.
- Meng Q, Raha A, Roy S et al. (2005). "IFN-gamma-stimulated transcriptional activation by IFN-gamma-activated transcriptional element-binding factor 1 occurs via an inducible interaction with CAAAT/enhancer-binding protein-beta.". J. Immunol. 174 (10): 6203–11. doi:10.4049/jimmunol.174.10.6203. PMID 15879117.
- Mehrle A, Rosenfelder H, Schupp I et al. (2006). "The LIFEdb database in 2006.". Nucleic Acids Res. 34 (Database issue): D415–8. doi:10.1093/nar/gkj139. PMC 1347501. PMID 16381901.
- Gerhard DS, Wagner L, Feingold EA et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
- Oh JH, Yang JO, Hahn Y et al. (2005). "Transcriptome analysis of human gastric cancer.". Mamm. Genome 16 (12): 942–54. doi:10.1007/s00335-005-0075-2. PMID 16341674.
- Wiemann S, Arlt D, Huber W et al. (2004). "From ORFeome to biology: a functional genomics pipeline.". Genome Res. 14 (10B): 2136–44. doi:10.1101/gr.2576704. PMC 528930. PMID 15489336.
- Chaudhry UA, Zhuang H, Crain BJ, Doré S (2008). "Elevated microsomal prostaglandin-E synthase-1 in Alzheimer's disease.". Alzheimer's & dementia : the journal of the Alzheimer's Association 4 (1): 6–13. doi:10.1016/j.jalz.2007.10.015. PMC 2500207. PMID 18631945.
- Nitz I, Fisher E, Grallert H et al. (2007). "Association of prostaglandin E synthase 2 (PTGES2) Arg298His polymorphism with type 2 diabetes in two German study populations.". J. Clin. Endocrinol. Metab. 92 (8): 3183–8. doi:10.1210/jc.2006-2550. PMID 17566096.
- Colombe L, Vindrios A, Michelet JF, Bernard BA (2007). "Prostaglandin metabolism in human hair follicle.". Exp. Dermatol. 16 (9): 762–9. doi:10.1111/j.1600-0625.2007.00586.x. PMID 17697149.
- Fisher E, Nitz I, Lindner I et al. (2007). "Candidate gene association study of type 2 diabetes in a nested case-control study of the EPIC-Potsdam cohort — role of fat assimilation.". Mol Nutr Food Res 51 (2): 185–91. doi:10.1002/mnfr.200600162. PMID 17266179.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.