{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T01:17:01Z","timestamp":1768526221643,"version":"3.49.0"},"reference-count":50,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2021,10,5]],"date-time":"2021-10-05T00:00:00Z","timestamp":1633392000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81974120 and 81570788"],"award-info":[{"award-number":["81974120 and 81570788"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["N162004005"],"award-info":[{"award-number":["N162004005"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Liver-specific deficiency of B-cell receptor-associated protein 31 knockout mice (BAP31-LKO) and the littermates were injected with acetaminophen (APAP), markers of liver injury, and the potential molecular mechanisms were determined. In response to APAP overdose, serum aspartate aminotransferase and alanine aminotransferase levels were increased in BAP31-LKO mice than in wild-type controls, accompanied by enhanced liver necrosis. APAP-induced apoptosis and mortality were increased. Hepatic glutathione was decreased (1.60 \u00b1 0.31 \u03bcmol\/g tissue in WT mice vs. 0.85 \u00b1 0.14 \u03bcmol\/g tissue in BAP31-LKO mice at 6 h, p &lt; 0.05), along with reduced glutathione reductase activity and superoxide dismutase; while malondialdehyde was significantly induced (0.41 \u00b1 0.03 nmol\/mg tissue in WT mice vs. 0.50 \u00b1 0.05 nmol\/mg tissue in BAP31-LKO mice for 6 h, p &lt; 0.05). JNK signaling activation and APAP-induced hepatic inflammation were increased in BAP31-LKO mice. The mechanism research revealed that BAP31-deficiency decreased Nrf2 mRNA stability (half-life of Nrf2 mRNA decreased from ~1.3 h to ~40 min) and miR-223 expression, led to reduced nuclear factor erythroid 2-related factor 2 (Nrf2) signaling activation and antioxidant genes induction. BAP31-deficiency decreased mitochondrial membrane potentials, reduced mitochondria-related genes expression, and resulted in mitochondrial dysfunction in the liver. Conclusions: BAP31-deficiency reduced the antioxidant response and Nrf2 signaling activation via reducing Nrf2 mRNA stabilization, enhanced JNK signaling activation, hepatic inflammation, and apoptosis, amplified APAP-induced hepatotoxicity in mice.<\/jats:p>","DOI":"10.3390\/ijms221910788","type":"journal-article","created":{"date-parts":[[2021,10,7]],"date-time":"2021-10-07T16:23:58Z","timestamp":1633623838000},"page":"10788","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Hepatocyte-Specific Deficiency of BAP31 Amplified Acetaminophen-Induced Hepatotoxicity via Attenuating Nrf2 Signaling Activation in Mice"],"prefix":"10.3390","volume":"22","author":[{"given":"Jie","family":"Zhao","sequence":"first","affiliation":[{"name":"Institute of Biochemistry and Molecular Biology, College of Life and Health Sciences, Northeastern University, Shenyang 110819, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaotong","family":"Lv","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Molecular Biology, College of Life and Health Sciences, Northeastern University, Shenyang 110819, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Huo","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Molecular Biology, College of Life and Health Sciences, Northeastern University, Shenyang 110819, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaodi","family":"Hu","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Molecular Biology, College of Life and Health Sciences, Northeastern University, Shenyang 110819, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaochen","family":"Li","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Molecular Biology, College of Life and Health Sciences, Northeastern University, Shenyang 110819, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shizhuo","family":"Sun","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Molecular Biology, College of Life and Health Sciences, Northeastern University, Shenyang 110819, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xin","family":"Zhao","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Molecular Biology, College of Life and Health Sciences, Northeastern University, Shenyang 110819, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuewei","family":"Kong","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Molecular Biology, College of Life and Health Sciences, Northeastern University, Shenyang 110819, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3910-1306","authenticated-orcid":false,"given":"Jialin","family":"Xu","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Molecular Biology, College of Life and Health Sciences, Northeastern University, Shenyang 110819, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1586\/17512433.2014.904744","article-title":"A Perspective on the Epidemiology of Acetaminophen Exposure and Toxicity in the United States","volume":"7","author":"Blieden","year":"2014","journal-title":"Expert Rev. 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