Estrogen-related receptor gamma controls hepatic CB1 receptor-mediated CYP2E1 expression and oxidative liver injury by alcohol
DC Field | Value | Language |
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dc.contributor.author | Kim, Don-Kyu | - |
dc.contributor.author | Kim, Yong-Hoon | - |
dc.contributor.author | Jang, Hyun-Hee | - |
dc.contributor.author | Park, Jinyoung | - |
dc.contributor.author | Kim, Jung Ran | - |
dc.contributor.author | Koh, Minseob | - |
dc.contributor.author | Jeong, Won-Il | - |
dc.contributor.author | Koo, Seung-Hoi | - |
dc.contributor.author | Park, Tae-Sik | - |
dc.contributor.author | Yun, Chul-Ho | - |
dc.contributor.author | Park, Seung Bum | - |
dc.contributor.author | Chiang, John Y. L. | - |
dc.contributor.author | Lee, Chul-Ho | - |
dc.contributor.author | Choi, Hueng-Sik | - |
dc.date.available | 2020-02-28T23:44:29Z | - |
dc.date.created | 2020-02-06 | - |
dc.date.issued | 2013-07 | - |
dc.identifier.issn | 0017-5749 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/14446 | - |
dc.description.abstract | Background 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 gamma (ERR gamma) is a constitutively active transcriptional activator regulating gene expression. Objective To investigate the role of ERR gamma in the alcohol-mediated regulation of CYP2E1 and to examine the possibility to control alcohol-mediated oxidative stress and liver injury through an ERR gamma 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 ERR gamma gene expression induced by alcohol-mediated activation of CB1 receptor results in induction of CYP2E1, while liver-specific ablation of ERR. gene expression blocks alcohol-induced expression of CYP2E1 in mouse liver. An ERR gamma 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 beneficial effects of the inverse agonist. Finally, chronic alcohol-mediated ERR gamma and CYP2E1 gene expression, ROS generation and liver injury in normal mice were nearly abolished in CB1(-/-) mice. Conclusions ERR gamma, 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.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | BMJ PUBLISHING GROUP | - |
dc.relation.isPartOf | GUT | - |
dc.subject | CYTOCHROME-P450 2E1 | - |
dc.subject | ERR-GAMMA | - |
dc.subject | FATTY LIVER | - |
dc.subject | CANNABINOID RECEPTOR | - |
dc.subject | RAT-LIVER | - |
dc.subject | IN-VIVO | - |
dc.subject | ACTIVATION | - |
dc.subject | ETHANOL | - |
dc.subject | MICE | - |
dc.subject | STRESS | - |
dc.title | Estrogen-related receptor gamma controls hepatic CB1 receptor-mediated CYP2E1 expression and oxidative liver injury by alcohol | - |
dc.type | Article | - |
dc.type.rims | ART | - |
dc.description.journalClass | 1 | - |
dc.identifier.wosid | 000319975900014 | - |
dc.identifier.doi | 10.1136/gutjnl-2012-303347 | - |
dc.identifier.bibliographicCitation | GUT, v.62, no.7, pp.1044 - 1054 | - |
dc.identifier.scopusid | 2-s2.0-84878759800 | - |
dc.citation.endPage | 1054 | - |
dc.citation.startPage | 1044 | - |
dc.citation.title | GUT | - |
dc.citation.volume | 62 | - |
dc.citation.number | 7 | - |
dc.contributor.affiliatedAuthor | Park, Tae-Sik | - |
dc.type.docType | Article | - |
dc.subject.keywordPlus | CYTOCHROME-P450 2E1 | - |
dc.subject.keywordPlus | ERR-GAMMA | - |
dc.subject.keywordPlus | FATTY LIVER | - |
dc.subject.keywordPlus | CANNABINOID RECEPTOR | - |
dc.subject.keywordPlus | RAT-LIVER | - |
dc.subject.keywordPlus | IN-VIVO | - |
dc.subject.keywordPlus | ACTIVATION | - |
dc.subject.keywordPlus | ETHANOL | - |
dc.subject.keywordPlus | MICE | - |
dc.subject.keywordPlus | STRESS | - |
dc.relation.journalResearchArea | Gastroenterology & Hepatology | - |
dc.relation.journalWebOfScienceCategory | Gastroenterology & Hepatology | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
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