Estrogen-related receptor gamma controls hepatic CB1 receptor-mediated CYP2E1 expression and oxidative liver injury by alcohol

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dc.contributor.authorD K Kim-
dc.contributor.authorYong Hoon Kim-
dc.contributor.authorH H Jang-
dc.contributor.authorJ Park-
dc.contributor.authorJ R Kim-
dc.contributor.authorM Koh-
dc.contributor.authorW I Jeong-
dc.contributor.authorS H Koo-
dc.contributor.authorT S Park-
dc.contributor.authorC H Yun-
dc.contributor.authorS B Park-
dc.contributor.authorJ Y L Chiang-
dc.contributor.authorChul Ho Lee-
dc.contributor.authorH S Choi-
dc.date.accessioned2017-04-19T09:40:19Z-
dc.date.available2017-04-19T09:40:19Z-
dc.date.issued2013-
dc.identifier.issn0017-5749-
dc.identifier.uri10.1136/gutjnl-2012-303347ko
dc.identifier.urihttps://oak.kribb.re.kr/handle/201005/11355-
dc.description.abstractBackground: The hepatic endocannabinoid system and cytochrome P450 2E1 (CYP2E1), a key enzyme causing alcohol-induced reactive oxygen species (ROS) generation, are major contributors to the pathogenesis of alcoholic liver disease. The nuclear hormone receptor oestrogen-related receptor γ (ERR?) is a constitutively active transcriptional activator regulating gene expression. Objective: To investigate the role of ERRa in the alcohol-mediated regulation of CYP2E1 and to examine the possibility to control alcohol-mediated oxidative stress and liver injury through an ERRγ inverse agonist. Design: For chronic alcoholic hepatosteatosis study, C57BL/6J wild-type and CB1-/- mice were administered alcohol for 4 weeks. GSK5182 and chlormethiazole (CMZ) were given by oral gavage for the last 2 weeks of alcohol feeding. Gene expression profiles and biochemical assays were performed using the liver or blood of mice. Results: Hepatic ERRγ gene expression induced by alcohol-mediated activation of CB1 receptor results in induction of CYP2E1, while liver-specific ablation of ERRγ gene expression blocks alcohol-induced expression of CYP2E1 in mouse liver. An ERRγ inverse agonist significantly ameliorates chronic alcohol-induced liver injury in mice through inhibition of CYP2E1-mediated generation of ROS, while inhibition of CYP2E1 by CMZ abrogates the bene ficial effects of the inverse agonist. Finally, chronic alcohol-mediated ERRγ and CYP2E1 gene expression, ROS generation and liver injury in normal mice were nearly abolished in CB1-/- mice. Conclusions: ERRγ, as a previously unrecognised transcriptional regulator of hepatic CB1 receptor, controls alcohol-induced oxidative stress and liver injury through CYP2E1 induction, and its inverse agonist could ameliorate oxidative liver injury due to chronic alcohol exposure.-
dc.publisherBmj Publishing Group-
dc.titleEstrogen-related receptor gamma controls hepatic CB1 receptor-mediated CYP2E1 expression and oxidative liver injury by alcohol-
dc.title.alternativeEstrogen-related receptor gamma controls hepatic CB1 receptor-mediated CYP2E1 expression and oxidative liver injury by alcohol-
dc.typeArticle-
dc.citation.titleGut-
dc.citation.number7-
dc.citation.endPage1054-
dc.citation.startPage1044-
dc.citation.volume62-
dc.contributor.affiliatedAuthorYong Hoon Kim-
dc.contributor.affiliatedAuthorChul Ho Lee-
dc.contributor.alternativeName김돈규-
dc.contributor.alternativeName김용훈-
dc.contributor.alternativeName장현희-
dc.contributor.alternativeName박진영-
dc.contributor.alternativeName김정란-
dc.contributor.alternativeName고민섭-
dc.contributor.alternativeName정원일-
dc.contributor.alternativeName구승회-
dc.contributor.alternativeName박태식-
dc.contributor.alternativeName윤철호-
dc.contributor.alternativeName박승범-
dc.contributor.alternativeNameChiang-
dc.contributor.alternativeName이철호-
dc.contributor.alternativeName최흥식-
dc.identifier.bibliographicCitationGut, vol. 62, no. 7, pp. 1044-1054-
dc.identifier.doi10.1136/gutjnl-2012-303347-
dc.description.journalClassY-
Appears in Collections:
Ochang Branch Institute > Division of National Bio-Infrastructure > Laboratory Animal Resource & Research Center > 1. Journal Articles
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