{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T00:40:32Z","timestamp":1791420032398,"version":"4.3.3"},"reference-count":0,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":5236,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2001,5]]},"abstract":"<jats:sec>\n            <jats:title\/>\n            <jats:p>The UDP\u2013glucuronosyltransferase, UGT1A1, is the critical enzyme responsible for detoxification of the potentially neurotoxic bilirubin by conjugating it with glucuronic acid. For decades, phenobarbital (PB) treatment for hyperbilirubinemia has been known to increase expression of the <jats:italic toggle=\"yes\">UGT1A1<\/jats:italic> gene in liver. We have now delineated the PB response activity to a 290\u2013bp distal enhancer sequence (-3483\/-3194) of the <jats:italic toggle=\"yes\">UGT1A1<\/jats:italic> gene. The enhancer contains 3 putative nuclear receptor motifs, and it was activated by the nuclear orphan receptor, human constitutive active receptor (hCAR), in cotransfected HepG2 cells. Bacterially expressed hCAR, acting as a heterodimer with <jats:italic toggle=\"yes\">in vitro<\/jats:italic>-translated retinoid X receptor (RXR\u03b1), only bound to 1 of the 3 NR motifs, named gtNR1 in a gel\u2013shift assay. Consistently, mutations of the gtNR1 site significantly decreased the activation by hCAR of the 290\u2013bp DNA in transfection assays. Moreover, the 290\u2013bp DNA was effectively activated in mouse primary hepatocytes in response to PB, offering an excellent clinical test for the examination of the responsiveness of the <jats:italic toggle=\"yes\">UGT1A1<\/jats:italic> to PB in the human population, particularly individuals with hyperbilirubinemia. (Hepatology 2001;33:1232\u20131238.)<\/jats:p>\n          <\/jats:sec>","DOI":"10.1053\/jhep.2001.24172","type":"journal-article","created":{"date-parts":[[2002,8,25]],"date-time":"2002-08-25T03:46:10Z","timestamp":1030247170000},"page":"1232-1238","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":333,"title":["The Phenobarbital Response Enhancer Module in the Human Bilirubin Udp\u2013Glucuronosyltransferase Ugt1a1 Gene and Regulation by the Nuclear Receptor Car"],"prefix":"10.1097","volume":"33","author":[{"given":"Junko","family":"Sugatani","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Kojima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akiko","family":"Ueda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoru","family":"Kakizaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kouichi","family":"Yoshinari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi-Hui","family":"Gong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ida S.","family":"Owens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiko","family":"Negishi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuya","family":"Sueyoshi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","container-title":["Hepatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1053%2Fjhep.2001.24172","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.lww.com\/01515467-200105000-00029","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,1]],"date-time":"2024-12-01T11:34:42Z","timestamp":1733052882000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.lww.com\/01515467-200105000-00029"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2001,5]]},"references-count":0,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2001]]}},"URL":"https:\/\/doi.org\/10.1053\/jhep.2001.24172","relation":{},"ISSN":["0270-9139"],"issn-type":[{"value":"0270-9139","type":"print"}],"subject":[],"published":{"date-parts":[[2001,5]]}}}