{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T07:43:43Z","timestamp":1762069423216,"version":"build-2065373602"},"reference-count":43,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2022,10,4]],"date-time":"2022-10-04T00:00:00Z","timestamp":1664841600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation (NRF) of Korea","doi-asserted-by":"publisher","award":["NRF-2020R1A2C3006952"],"award-info":[{"award-number":["NRF-2020R1A2C3006952"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Acetaminophen (APAP) is a widely used analgesic and antipyretic drug, but its overdose can cause acute liver failure. The dosage-sensitive sex reversal adrenal hypoplasia congenita critical region on the X chromosome, gene 1 (DAX-1, NR0B1), is an orphan nuclear receptor that acts as a transcriptional co-repressor of various genes. In this study, we identified the role of DAX-1 in APAP-induced liver injury using hepatocyte-specific Dax-1 knockout (Dax-1 LKO) mice. Mouse primary hepatocytes were used as a comparative in vitro study. APAP overdose led to decreased plasma alanine aminotransferase and aspartate aminotransferase levels in Dax-1 LKO mice compared to C57BL\/6J (WT) controls, accompanied by reduced liver necrosis. The expression of the genes encoding the enzymes catalyzing glutathione (GSH) synthesis and metabolism and antioxidant enzymes was increased in the livers of APAP-treated Dax-1 LKO mice. The rapid recovery of GSH levels in the mitochondrial fraction of APAP-treated Dax-1 LKO mice led to reduced reactive oxygen species levels, resulting in the inhibition of the prolonged JNK activation. The hepatocyte-specific DAX-1 deficiency increased the protein expression of nuclear factor erythroid 2-related factor 2 (Nrf2) compared with WT controls after APAP administration. These results indicate that DAX-1 deficiency in hepatocytes protects against APAP-induced liver injury by Nrf2-regulated antioxidant defense.<\/jats:p>","DOI":"10.3390\/ijms231911786","type":"journal-article","created":{"date-parts":[[2022,10,8]],"date-time":"2022-10-08T23:39:31Z","timestamp":1665272371000},"page":"11786","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Hepatocyte-Specific Deficiency of DAX-1 Protects Mice from Acetaminophen-Induced Hepatotoxicity by Activating NRF2 Signaling"],"prefix":"10.3390","volume":"23","author":[{"given":"Young-Joo","family":"Suh","sequence":"first","affiliation":[{"name":"Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Korea"},{"name":"College of Veterinary Medicine, Chungnam National University, Daejeon 34134, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hyo-Jeong","family":"Yun","sequence":"additional","affiliation":[{"name":"Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Korea"},{"name":"Department of Functional Genomics, KRIBB School of Bioscience, University of Science and Technology (UST), Daejeon 34113, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu-Bin","family":"Kim","sequence":"additional","affiliation":[{"name":"Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eun-Jung","family":"Kang","sequence":"additional","affiliation":[{"name":"Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jung Hyeon","family":"Choi","sequence":"additional","affiliation":[{"name":"Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Young-Keun","family":"Choi","sequence":"additional","affiliation":[{"name":"Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"In-Bok","family":"Lee","sequence":"additional","affiliation":[{"name":"Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dong-Hee","family":"Choi","sequence":"additional","affiliation":[{"name":"Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yun Jeong","family":"Seo","sequence":"additional","affiliation":[{"name":"Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jung-Ran","family":"Noh","sequence":"additional","affiliation":[{"name":"Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5119-0711","authenticated-orcid":false,"given":"Jong-Soo","family":"Lee","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Chungnam National University, Daejeon 34134, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yong-Hoon","family":"Kim","sequence":"additional","affiliation":[{"name":"Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Korea"},{"name":"Department of Functional Genomics, KRIBB School of Bioscience, University of Science and Technology (UST), Daejeon 34113, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6996-5746","authenticated-orcid":false,"given":"Chul-Ho","family":"Lee","sequence":"additional","affiliation":[{"name":"Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Korea"},{"name":"Department of Functional Genomics, KRIBB School of Bioscience, University of Science and Technology (UST), Daejeon 34113, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,4]]},"reference":[{"key":"ref_1","first-page":"131","article-title":"Acetaminophen-Induced Hepatotoxicity: A Comprehensive Update","volume":"4","author":"Yoon","year":"2016","journal-title":"J. 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