{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T08:56:39Z","timestamp":1762160199037},"reference-count":50,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2009,1,29]],"date-time":"2009-01-29T00:00:00Z","timestamp":1233187200000},"content-version":"vor","delay-in-days":1703,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2004,6]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>Using gene chip technology, we first identified that PGF<jats:sub>2<jats:italic>\u03b1<\/jats:italic><\/jats:sub> (FP agonist) and Butaprost (EP<jats:sub>2<\/jats:sub> agonist) induced about a five\u2010fold upregulation of Nur77 mRNA expression in hFP\u2010HEK 293\/EBNA and hEP<jats:sub>2<\/jats:sub>\u2010HEK293\/EBNA cells. Northern Blot analysis revealed that PGF<jats:sub>2<jats:italic>\u03b1<\/jats:italic><\/jats:sub>\u2010 and Butaprost\u2010induced upregulation of Nur77 expression are dose\u2010 and time\u2010dependent.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Both PGF<jats:sub>2<jats:italic>\u03b1<\/jats:italic><\/jats:sub> and Butaprost upregulated Nur77 gene expression through the protein kinase C (PKC) pathway. These data are the first showing a link between EP<jats:sub>2<\/jats:sub> receptor stimulation and protein kinase C activation. Calcineurin was found to be involved downstream of the PKC pathway in PGF<jats:sub>2<jats:italic>\u03b1<\/jats:italic><\/jats:sub>\u2010induced Nur77 expression, but not in Butaprost\u2010induced Nur77 expression.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>We also used Nur77 as a marker gene to compare the effects of PGF<jats:sub>2<jats:italic>\u03b1<\/jats:italic><\/jats:sub>, Butaprost, and Bimatoprost (a prostamide) on Nur77 expression in human primary trabecular meshwork and ciliary smooth muscle (SM) cells, which are target cells for antiglaucoma drugs. The results showed that PGF<jats:sub>2<jats:italic>\u03b1<\/jats:italic><\/jats:sub> and Butaprost, but not Bimatoprost, induced upregulation of Nur77 expression in human TM cells. PGF<jats:sub>2<jats:italic>\u03b1<\/jats:italic><\/jats:sub>, but not Bimatoprost, dramatically induced upregulation of Nur77 mRNA expression in human ciliary SM cells, whereas Butaprost slightly upregulated Nur77 mRNA expression in SM cells.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Nur77 promoter deletion analysis indicated that PGF<jats:sub>2<jats:italic>\u03b1<\/jats:italic><\/jats:sub>, but not Bimatoprost, activated Nur77 promoter\u2010luciferase reporter in hFP\u2010HEK 293\/EBNA cells. Butaprost was less efficacious in inducing Nur77 promoter\u2010luciferase reporter activity in hEP<jats:sub>2<\/jats:sub>\u2010HEK293\/EBNA cells relative to PGF<jats:sub>2<jats:italic>\u03b1<\/jats:italic><\/jats:sub> in the comparable assay. The data for Nur77 promoter functional analysis were matched to the Northern blot analysis.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>It appears that PGF<jats:sub>2<jats:italic>\u03b1<\/jats:italic><\/jats:sub> and Butaprost activate Nur77 transcription mechanisms through the activation of FP and EP<jats:sub>2<\/jats:sub> receptor\u2010coupled signaling pathways, whereas Bimatoprost stimulates neither FP nor EP<jats:sub>2<\/jats:sub> receptors.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (2004) <jats:bold>142<\/jats:bold>, 737\u2013748. doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0705829\">10.1038\/sj.bjp.0705829<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0705829","type":"journal-article","created":{"date-parts":[[2004,6,17]],"date-time":"2004-06-17T17:18:11Z","timestamp":1087492691000},"page":"737-748","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Upregulation of orphan nuclear receptor Nur77 following PGF<sub>2<i>\u03b1<\/i><\/sub>, Bimatoprost, and Butaprost treatments. Essential role of a protein kinase C pathway involved in EP<sub>2<\/sub> receptor activated Nur77 gene transcription"],"prefix":"10.1111","volume":"142","author":[{"given":"Yanbin","family":"Liang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chen","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Victor M","family":"Guzman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William W","family":"Chang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Albert J","family":"Evinger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jozelyn V","family":"Pablo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David F","family":"Woodward","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2009,1,29]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1388-1981(99)00164-X"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.2.1179"},{"key":"e_1_2_6_4_1","first-page":"1841","article-title":"Reliable measurement of mouse intraocular pressure by a servo\u2010null micropipette system","volume":"42","author":"AVILA M.Y.","year":"2001","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4615-4793-8_77"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/357695a0"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R000024200"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/00061198-199201020-00006"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1210\/me.7.8.953"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1210\/mend-5-6-854"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0039-6257(01)00212-0"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.10.12.6454"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M003467200"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109440200"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1001\/archopht.119.8.1165"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.85.22.8444"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.1976.56.4.595"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.50.31278"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0169-328X(01)00116-4"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M301009200"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/367281a0"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(95)90199-X"},{"key":"e_1_2_6_23_1","first-page":"1237","article-title":"The NGFI\u2010B subfamily of the nuclear receptor superfamily","volume":"12","author":"MARUYAMA K.","year":"1998","journal-title":"Int. J. Oncol."},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.103.061705"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(88)90138-9"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9394(02)01827-5"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1037343100"},{"key":"e_1_2_6_28_1","doi-asserted-by":"crossref","first-page":"16491","DOI":"10.1016\/S0021-9258(18)42029-7","article-title":"Domains regulating transcriptional activity of the inducible orphan receptor NGFI\u2010B","volume":"267","author":"PAULSEN R.E.","year":"1992","journal-title":"J. Biol. Chem."},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.9.7.769"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-6147(00)89035-5"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-291X(03)00931-8"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.02-1281"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.301.3.900"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/0163-7258(91)90054-P"},{"key":"e_1_2_6_35_1","first-page":"1134","article-title":"From PGF(2alpha)\u2010isopropyl ester to latanoprost: a review of the development of xalatan: the Proctor Lecture","volume":"42","author":"STJERNSCHANTZ J.W.","year":"2001","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(95)00129-W"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.10.5427"},{"key":"e_1_2_6_38_1","first-page":"716","article-title":"Metalloproteinase gene transcription in human ciliary muscle cells with latanoprost","volume":"43","author":"WEINREB R.N.","year":"2002","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"e_1_2_6_39_1","first-page":"6124","article-title":"Involvement of JunD in transcriptional activation of the orphan receptor gene nur77 by nerve growth factor and membrane depolarization in PC12 cells","volume":"13","author":"WILLIAM G.T.","year":"1993","journal-title":"Mol. Cell. Biol."},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1925541"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1006\/exer.1993.1052"},{"key":"e_1_2_6_42_1","doi-asserted-by":"publisher","DOI":"10.1089\/jop.1995.11.447"},{"key":"e_1_2_6_43_1","first-page":"1838","article-title":"Prostaglandin F2 alpha effects on intraocular pressure negatively correlate with FP\u2010receptor stimulation","volume":"30","author":"WOODWARD D.F.","year":"1989","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"e_1_2_6_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0039-6257(01)00224-7"},{"key":"e_1_2_6_45_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.102.047837"},{"key":"e_1_2_6_46_1","first-page":"545","article-title":"Intraocular pressure effects of selective prostanoid receptor agonists involve different receptor subtypes according to radioligand binding studies","volume":"6","author":"WOODWARD D.F.","year":"1993","journal-title":"J. Lipid Med."},{"key":"e_1_2_6_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(93)90569-4"},{"key":"e_1_2_6_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/367277a0"},{"key":"e_1_2_6_49_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.15.11.6364"},{"key":"e_1_2_6_50_1","doi-asserted-by":"crossref","first-page":"9148","DOI":"10.1016\/S0021-9258(18)52990-2","article-title":"Transcriptional activation of the inducible nuclear receptor gene nur77 by nerve growth factor and membrane depolarization in PC12 cells","volume":"268","author":"YOON J.K.","year":"1993","journal-title":"J. Biol. Chem."},{"key":"e_1_2_6_51_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.34.21181"}],"container-title":["British Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1038%2Fsj.bjp.0705829","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1038%2Fsj.bjp.0705829","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1038\/sj.bjp.0705829","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,13]],"date-time":"2023-10-13T20:37:03Z","timestamp":1697229423000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1038\/sj.bjp.0705829"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,6]]},"references-count":50,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2004,6]]}},"alternative-id":["10.1038\/sj.bjp.0705829"],"URL":"https:\/\/doi.org\/10.1038\/sj.bjp.0705829","archive":["Portico"],"relation":{},"ISSN":["0007-1188","1476-5381"],"issn-type":[{"value":"0007-1188","type":"print"},{"value":"1476-5381","type":"electronic"}],"subject":[],"published":{"date-parts":[[2004,6]]},"assertion":[{"value":"2009-01-29","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}