1 40 1 Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. URL Address <a href="http://doi.org/10.1136/gutjnl-2012-303347" target="_blank" rel="noreferrer noopener">http://doi.org/10.1136/gutjnl-2012-303347</a> Pages 1044–1054 Issue 7 Volume 62 Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Estrogen-related receptor gamma controls hepatic CB1 receptor-mediated CYP2E1 expression and oxidative liver injury by alcohol. Publisher An entity responsible for making the resource available Gut Date A point or period of time associated with an event in the lifecycle of the resource 2013 2013-07 Subject The topic of the resource Alcohol-Induced Injury; Alcoholic Liver Disease; Alcoholic/genetics/*metabolism/prevention & control; Animals; Cannabinoid; CB1/*physiology; Cytochrome P-450 CYP2E1 Inhibitors; Cytochrome P-450 CYP2E1/genetics/*metabolism; Enzyme Inhibitors/pharmacology/therapeutic use; Enzymologic/drug effects/physiology; Estrogen/deficiency/genetics/*physiology; Ethanol/pharmacology; Gene Expression Profiling/methods; Gene Expression Regulation; Gene Regulation; Genetic/physiology; Inbred C57BL; Knockout; Liver; Liver Diseases; Liver Metabolism; Liver/metabolism; Male; Mice; Oxidation-Reduction; Oxidative Stress/physiology; Receptor; Receptors; Signal Transduction/drug effects/physiology; Tamoxifen/analogs & derivatives/pharmacology/therapeutic use; Transcription Creator An entity primarily responsible for making the resource Kim Don-Kyu; Kim Yong-Hoon; Jang Hyun-Hee; Park Jinyoung; Kim Jung Ran; Koh Minseob; Jeong Won-Il; Koo Seung-Hoi; Park Tae-Sik; Yun Chul-Ho; Park Seung Bum; Chiang John Y L; Lee Chul-Ho; Choi Hueng-Sik Description An account of the resource 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 (ERRgamma) is a constitutively active transcriptional activator regulating gene expression. OBJECTIVE: To investigate the role of ERRgamma in the alcohol-mediated regulation of CYP2E1 and to examine the possibility to control alcohol-mediated oxidative stress and liver injury through an ERRgamma 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 ERRgamma gene expression induced by alcohol-mediated activation of CB1 receptor results in induction of CYP2E1, while liver-specific ablation of ERRgamma gene expression blocks alcohol-induced expression of CYP2E1 in mouse liver. An ERRgamma 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 ERRgamma and CYP2E1 gene expression, ROS generation and liver injury in normal mice were nearly abolished in CB1(-/-) mice. CONCLUSIONS: ERRgamma, 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. Identifier An unambiguous reference to the resource within a given context <a href="http://doi.org/10.1136/gutjnl-2012-303347" target="_blank" rel="noreferrer noopener">10.1136/gutjnl-2012-303347</a> Rights Information about rights held in and over the resource Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s). 2013 Alcohol-Induced Injury Alcoholic Liver Disease Alcoholic/genetics/*metabolism/prevention & control Animals Cannabinoid CB1/*physiology Chiang John Y L Choi Hueng-Sik Cytochrome P-450 CYP2E1 Inhibitors Cytochrome P-450 CYP2E1/genetics/*metabolism Department of Integrative Medical Sciences Enzyme Inhibitors/pharmacology/therapeutic use Enzymologic/drug effects/physiology Estrogen/deficiency/genetics/*physiology Ethanol/pharmacology Gene Expression Profiling/methods Gene Expression Regulation Gene Regulation Genetic/physiology Gut Inbred C57BL Jang Hyun-Hee Jeong Won-Il Kim Don-Kyu Kim Jung Ran Kim Yong-Hoon Knockout Koh Minseob Koo Seung-Hoi Lee Chul-Ho Liver Liver Diseases Liver Metabolism Liver/metabolism Male Mice NEOMED College of Medicine Oxidation-Reduction Oxidative Stress/physiology Park Jinyoung Park Seung Bum Park Tae-Sik Receptor Receptors Signal Transduction/drug effects/physiology Tamoxifen/analogs & derivatives/pharmacology/therapeutic use Transcription Yun Chul-Ho