{"doi":"10.3390/ijms231911786","title":"Hepatocyte-Specific Deficiency of DAX-1 Protects Mice from Acetaminophen-Induced Hepatotoxicity by Activating NRF2 Signaling","abstract":"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.","journal":"International Journal of Molecular Sciences","year":2022,"id":292143,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9484,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":976324,"name":"Hyo-Jeong Yun","orcid":null,"position":1,"is_corresponding":false},{"id":975830,"name":"Yu Bin Kim","orcid":"0000-0001-6325-6191","position":2,"is_corresponding":false},{"id":975831,"name":"Eunjung Kang","orcid":"0000-0002-0265-1144","position":3,"is_corresponding":false},{"id":976325,"name":"Jung Hyeon Choi","orcid":null,"position":4,"is_corresponding":false},{"id":40450,"name":"Young‐Keun Choi","orcid":null,"position":5,"is_corresponding":false},{"id":975832,"name":"In-Bok Lee","orcid":"0000-0002-0401-7657","position":6,"is_corresponding":false},{"id":975833,"name":"Dong‐Hee Choi","orcid":"0000-0002-2418-9560","position":7,"is_corresponding":false},{"id":976326,"name":"Yun Jeong Seo","orcid":null,"position":8,"is_corresponding":false},{"id":976327,"name":"Jung‐Ran Noh","orcid":null,"position":9,"is_corresponding":false},{"id":399439,"name":"Jong‐Soo Lee","orcid":"0000-0001-5119-0711","position":10,"is_corresponding":false},{"id":880651,"name":"Yong‐Hoon Kim","orcid":"0000-0001-5209-4908","position":11,"is_corresponding":false},{"id":453161,"name":"Chul‐Ho Lee","orcid":"0000-0002-6996-5746","position":12,"is_corresponding":false},{"id":976323,"name":"Young-Joo Suh","orcid":null,"position":0,"is_corresponding":true}],"reference_count":45,"raw_metadata":null,"created_at":"2026-07-19T00:30:42.221508Z","pmid":"36233086","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}