{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T03:16:58Z","timestamp":1772507818414,"version":"3.50.1"},"reference-count":45,"publisher":"Wiley","issue":"20","license":[{"start":{"date-parts":[[2025,1,30]],"date-time":"2025-01-30T00:00:00Z","timestamp":1738195200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>Endoplasmic reticulum (ER) stress is a crucial pathogenic mechanism in alcoholic liver disease (ALD). B\u2010cell receptor\u2010associated protein 31 (BAP31) can regulate ER homeostasis and anti\u2010apoptosis, but the function and regulation of BAP31 in ALD are unclear. The purpose of this study is to investigate whether BAP31 deacetylation by sirtuin 2 could attenuate ER stress and apoptosis during ALD and to explore whether carnosol could alleviate ALD through the sirtuin 2\/BAP31 pathway.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>A mouse model of ALD was established by feeding mice with alcoholic liquid chow. In vitro, AML\u201012 cells were stimulated with alcohol. The therapeutic efficacy of carnosol in protecting mice from ALD pathogenesis was evaluated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Treatment with carnosol protected mice against ALD and attenuated hepatocyte ER stress and apoptosis. Carnosol up\u2010regulated sirtuin 2 expression, and sirtuin 2knockdown abolished the protective effect of carnosol during ALD. Moreover, sirtuin 2 knockdown reduced BAP31 expression. Carnosol\u2010mediated BAP31 up\u2010regulation was abolished upon knockdown of sirtuin 2. Mechanistically, sirtuin 2 selectively regulates the deacetylation of BAP31 at K158.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion and Implications<\/jats:title><jats:p>Taken together, the present study shows for the first time that carnosol exerts its protective efficacy through facilitating sirtuin 2\u2010mediated deacetylation of BAP31 at K158 to attenuate hepatocyte ER stress and apoptosis during ALD. These results provide new therapeutic targets and approaches for combating chronic ALD.<\/jats:p><\/jats:sec><jats:sec><jats:title>LINKED ARTICLES<\/jats:title><jats:p>This article is part of a themed issue Drugs and Drug Targets in Metabolic and Chronic Inflammatory Diseases. To view the other articles in this section visit <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bph.v182.20\/issuetoc\">http:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bph.v182.20\/issuetoc<\/jats:ext-link><\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.17432","type":"journal-article","created":{"date-parts":[[2025,1,30]],"date-time":"2025-01-30T03:55:32Z","timestamp":1738209332000},"page":"5023-5037","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Deacetylation of BAP31 by sirtuin 2 attenuates apoptosis of hepatocytes induced by endoplasmic reticulum stress, in chronic alcoholic liver injury"],"prefix":"10.1111","volume":"182","author":[{"given":"Sai","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Pharmacy Jinshan Hospital, Fudan University  Shanghai China"},{"name":"Department of Pharmacology Dalian Medical University  Dalian China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yufeng","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Dalian Medical University  Dalian China"},{"name":"Department of Pharmacy The Second Hospital of Dalian Medical University  Dalian China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wen","family":"Shan","sequence":"additional","affiliation":[{"name":"Department of Pharmacy The Second Hospital of Dalian Medical University  Dalian China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guoyang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Dalian Medical University  Dalian China"},{"name":"Department of Pharmacy The Second Hospital of Dalian Medical University  Dalian China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ran","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Pharmacy The Second Hospital of Dalian Medical University  Dalian China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhecheng","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Dalian Medical University  Dalian China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Dalian Medical University  Dalian China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5940-9167","authenticated-orcid":false,"given":"Jihong","family":"Yao","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Dalian Medical University  Dalian China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ning","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Jinshan Hospital, Fudan University  Shanghai China"},{"name":"Department of Pharmacology Dalian Medical University  Dalian China"},{"name":"Department of Pharmacy The Second Hospital of Dalian Medical University  Dalian China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,1,30]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.16181"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.16180"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.16176"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14112"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cld.2016.02.006"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2018.01.127"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.30866"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15868"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-015-9519-1"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/mnfr.201500878"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2021.115758"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/acer.13840"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v20.i9.2143"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0016-5085(03)00276-2"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/ptr.7749"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2011.02.005"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2019.06.019"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23126790"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15178"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2019.01042"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0891-5849(00)00503-7"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.biochem.7b00859"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox11122341"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2021.119997"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15193"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biochi.2021.04.008"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.31773"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41418-018-0069-8"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tox.2021.152923"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.15.1219"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2020.04.038"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1097\/00042737-200209000-00011"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M501306200"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v20.i36.12934"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2021.115729"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.24409"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.31197"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-02537-6"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19082291"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2020.105218"},{"key":"e_1_2_12_42_1","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M077016"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41551-019-0375-6"},{"key":"e_1_2_12_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxlet.2016.12.010"},{"key":"e_1_2_12_45_1","doi-asserted-by":"publisher","DOI":"10.1177\/1535370216642039"},{"key":"e_1_2_12_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2017.10.013"}],"container-title":["British Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bph.17432","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,15]],"date-time":"2025-09-15T02:33:34Z","timestamp":1757903614000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1111\/bph.17432"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,30]]},"references-count":45,"journal-issue":{"issue":"20","published-print":{"date-parts":[[2025,10]]}},"alternative-id":["10.1111\/bph.17432"],"URL":"https:\/\/doi.org\/10.1111\/bph.17432","archive":["Portico"],"relation":{},"ISSN":["0007-1188","1476-5381"],"issn-type":[{"value":"0007-1188","type":"print"},{"value":"1476-5381","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,30]]},"assertion":[{"value":"2023-10-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-11-23","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-01-30","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}