{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T18:28:12Z","timestamp":1789496892226,"version":"build-2803163510"},"reference-count":39,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,7,15]],"date-time":"2024-07-15T00:00:00Z","timestamp":1721001600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,7,15]],"date-time":"2024-07-15T00:00:00Z","timestamp":1721001600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100014717","name":"National Outstanding Youth Science Fund Project of National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82070609"],"award-info":[{"award-number":["82070609"]}],"id":[{"id":"10.13039\/100014717","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>This study explores the role of SIRT2 in regulating autophagy and its interaction with AMPK in the context of acute liver failure (ALF). This study investigated the effects of SIRT2 and AMPK on autophagy in ALF mice and TAA-induced AML12 cells. The results revealed that the liver tissue in ALF model group had a lot of inflammatory cell infiltration and hepatocytes necrosis, which were reduced by SIRT2 inhibitor AGK2. In comparison to normal group, the level of SIRT2, P62, MDA, TOS in TAA group were significantly increased, which were decreased in AGK2 treatment. Compared with normal group, the expression of P-PRKAA1, Becilin1 and LC3B-II was decreased in TAA group. However, AGK2 enhanced the expression of P-PRKAA1, Becilin1 and LC3B-II in model group. Overexpression of SIRT2 in AML12 cell resulted in decreased P-PRKAA1, Becilin1 and LC3B-II level, enhanced the level of SIRT2, P62, MDA, TOS. Overexpression of PRKAA1 in AML12 cell resulted in decreased SIRT2, TOS and MDA level and triggered more autophagy. In conclusion, the data suggested the link between AMPK and SIRT2, and reveals the important role of AMPK and SIRT2 in autophagy on acute liver failure.<\/jats:p>","DOI":"10.1038\/s41598-024-67102-w","type":"journal-article","created":{"date-parts":[[2024,7,15]],"date-time":"2024-07-15T09:02:16Z","timestamp":1721034136000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["The SIRT2-AMPK axis regulates autophagy induced by acute liver failure"],"prefix":"10.1038","volume":"14","author":[{"given":"Qingqi","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunxia","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danmei","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukun","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luwen","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zuojiong","family":"Gong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,7,15]]},"reference":[{"key":"67102_CR1","doi-asserted-by":"publisher","first-page":"617","DOI":"10.1016\/j.cvsm.2016.11.010","volume":"47","author":"V Thawley","year":"2017","unstructured":"Thawley, V. Acute liver injury and failure. Vet. Clin. North Am. Small Anim. Pract. 47, 617\u2013630 (2017).","journal-title":"Vet. Clin. North Am. Small Anim. Pract."},{"key":"67102_CR2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mam.2021.100973","volume":"82","author":"H Qian","year":"2021","unstructured":"Qian, H. et al. Autophagy in liver diseases: A review. Mol. Aspects Med. 82, 100973 (2021).","journal-title":"Mol. Aspects Med."},{"key":"67102_CR3","doi-asserted-by":"publisher","first-page":"354","DOI":"10.1016\/j.jhep.2016.04.025","volume":"65","author":"HM Ni","year":"2016","unstructured":"Ni, H. M. et al. Removal of acetaminophen protein adducts by autophagy protects against acetaminophen-induced liver injury in mice. J. Hepatol. 65, 354\u2013362 (2016).","journal-title":"J. Hepatol."},{"key":"67102_CR4","doi-asserted-by":"publisher","first-page":"1077","DOI":"10.1016\/j.jcmgh.2022.07.014","volume":"14","author":"X Li","year":"2022","unstructured":"Li, X. et al. FGL2-MCOLN3-autophagy axis-triggered neutrophil extracellular traps exacerbate liver injury in fulminant viral hepatitis. Cell Mol. Gastroenterol. Hepatol. 14, 1077\u20131101 (2022).","journal-title":"Cell Mol. Gastroenterol. Hepatol."},{"key":"67102_CR5","doi-asserted-by":"crossref","unstructured":"Zhang, C.-Y. et al. COX-2\/sEH dual inhibitor alleviates hepatocyte senescence in NAFLD mice by restoring autophagy through Sirt1\/PI3K\/AKT\/mTOR. Int. J. Mol. Sci. 23 (2022).","DOI":"10.3390\/ijms23158267"},{"key":"67102_CR6","doi-asserted-by":"publisher","DOI":"10.15252\/embj.2021108863","volume":"40","author":"DJ Klionsky","year":"2021","unstructured":"Klionsky, D. J. et al. Autophagy in major human diseases. EMBO J. 40, e108863 (2021).","journal-title":"EMBO J."},{"key":"67102_CR7","doi-asserted-by":"publisher","first-page":"1016","DOI":"10.1038\/ncb2329","volume":"13","author":"MM Mihaylova","year":"2011","unstructured":"Mihaylova, M. M. & Shaw, R. J. The AMPK signalling pathway coordinates cell growth, autophagy and metabolism. Nat. Cell Biol. 13, 1016\u20131023 (2011).","journal-title":"Nat. Cell Biol."},{"key":"67102_CR8","doi-asserted-by":"publisher","first-page":"132","DOI":"10.1038\/ncb2152","volume":"13","author":"J Kim","year":"2011","unstructured":"Kim, J., Kundu, M., Viollet, B. & Guan, K. L. AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1. Nat. Cell Biol. 13, 132\u2013141 (2011).","journal-title":"Nat. Cell Biol."},{"key":"67102_CR9","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1016\/j.semcancer.2013.05.007","volume":"23","author":"M Wirth","year":"2013","unstructured":"Wirth, M., Joachim, J. & Tooze, S. A. Autophagosome formation\u2013the role of ULK1 and Beclin1-PI3KC3 complexes in setting the stage. Semin Cancer Biol. 23, 301\u2013309 (2013).","journal-title":"Semin Cancer Biol."},{"key":"67102_CR10","doi-asserted-by":"publisher","first-page":"1363","DOI":"10.1111\/liv.13866","volume":"38","author":"X Chao","year":"2018","unstructured":"Chao, X., Wang, H., Jaeschke, H. & Ding, W. X. Role and mechanisms of autophagy in acetaminophen-induced liver injury. Liver Int. 38, 1363\u20131374 (2018).","journal-title":"Liver Int."},{"issue":"4","key":"67102_CR11","doi-asserted-by":"publisher","first-page":"825","DOI":"10.1016\/j.jhep.2014.05.033","volume":"61","author":"Z Lin","year":"2014","unstructured":"Lin, Z. et al. Adiponectin protects against acetaminophen-induced mitochondrial dysfunction and acute liver injury by promoting autophagy in mice. J. Hepatol. 61(4), 825\u2013831 (2014).","journal-title":"J. Hepatol."},{"key":"67102_CR12","doi-asserted-by":"publisher","first-page":"1114","DOI":"10.1080\/15548627.2015.1034406","volume":"11","author":"S Obba","year":"2015","unstructured":"Obba, S. et al. The PRKAA1\/AMPK\u03b11 pathway triggers autophagy during CSF1-induced human monocyte differentiation and is a potential target in CMML. Autophagy 11, 1114\u20131129 (2015).","journal-title":"Autophagy"},{"key":"67102_CR13","doi-asserted-by":"publisher","first-page":"3992","DOI":"10.1080\/15548627.2021.1899667","volume":"17","author":"W Wu","year":"2021","unstructured":"Wu, W. et al. TNF-induced necroptosis initiates early autophagy events via RIPK3-dependent AMPK activation, but inhibits late autophagy. Autophagy 17, 3992\u20134009 (2021).","journal-title":"Autophagy"},{"key":"67102_CR14","doi-asserted-by":"publisher","first-page":"100961","DOI":"10.1016\/j.arr.2019.100961","volume":"55","author":"Y Wang","year":"2019","unstructured":"Wang, Y., Yang, J., Hong, T., Chen, X. & Cui, L. SIRT2: Controversy and multiple roles in disease and physiology. Ageing Res. Rev. 55, 100961 (2019).","journal-title":"Ageing Res. Rev."},{"key":"67102_CR15","first-page":"1370","volume":"55","author":"G Fu","year":"2023","unstructured":"Fu, G. et al. PGAM5 deacetylation mediated by SIRT2 facilitates lipid metabolism and liver cancer proliferation. Acta Biochim Biophys. Sin. (Shanghai) 55, 1370\u20131379 (2023).","journal-title":"Acta Biochim Biophys. Sin. (Shanghai)"},{"key":"67102_CR16","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1038\/s41421-021-00326-6","volume":"7","author":"Y Zhang","year":"2021","unstructured":"Zhang, Y. et al. SIRT2-mediated deacetylation and deubiquitination of C\/EBPbeta prevents ethanol-induced liver injury. Cell Discov. 7, 93 (2021).","journal-title":"Cell Discov."},{"issue":"10","key":"67102_CR17","doi-asserted-by":"publisher","first-page":"8970","DOI":"10.3390\/ijms24108970","volume":"24","author":"X Li","year":"2023","unstructured":"Li, X. et al. SIRT2 deficiency aggravates diet-induced nonalcoholic fatty liver disease through modulating gut microbiota and metabolites. Int. J. Mol. Sci. 24(10), 8970 (2023).","journal-title":"Int. J. Mol. Sci."},{"key":"67102_CR18","doi-asserted-by":"publisher","first-page":"2051","DOI":"10.1161\/CIRCULATIONAHA.117.028728","volume":"136","author":"X Tang","year":"2017","unstructured":"Tang, X. et al. SIRT2 acts as a cardioprotective deacetylase in pathological cardiac hypertrophy. Circulation 136, 2051\u20132067 (2017).","journal-title":"Circulation"},{"key":"67102_CR19","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1007\/s00395-021-00887-3","volume":"116","author":"N Liu","year":"2021","unstructured":"Liu, N. et al. LncRNA LncHrt preserves cardiac metabolic homeostasis and heart function by modulating the LKB1-AMPK signaling pathway. Basic Res. Cardiol. 116, 48 (2021).","journal-title":"Basic Res. Cardiol."},{"key":"67102_CR20","doi-asserted-by":"publisher","first-page":"1145","DOI":"10.1093\/ndt\/gfaa042","volume":"35","author":"YJ Jung","year":"2020","unstructured":"Jung, Y. J., Park, W., Kang, K. P. & Kim, W. SIRT2 is involved in cisplatin-induced acute kidney injury through regulation of mitogen-activated protein kinase phosphatase-1. Nephrol. Dial. Transpl. 35, 1145\u20131156 (2020).","journal-title":"Nephrol. Dial. Transpl."},{"key":"67102_CR21","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1016\/j.hbpd.2023.03.003","volume":"23","author":"Q-Q Zhang","year":"2024","unstructured":"Zhang, Q.-Q. et al. AGK2 pre-treatment protects against thioacetamide-induced acute liver failure via regulating the MFN2-PERK axis and ferroptosis signaling pathway. Hepatobil. Pancreat. Dis. Int. 23, 43\u201351 (2024).","journal-title":"Hepatobil. Pancreat. Dis. Int."},{"key":"67102_CR22","doi-asserted-by":"publisher","DOI":"10.1096\/fj.202002421R","volume":"35","author":"P Viswanathan","year":"2021","unstructured":"Viswanathan, P., Sharma, Y., Jaber, F.-L., Tchaikovskaya, T. & Gupta, S. Transplanted hepatocytes rescue mice in acetaminophen-induced acute liver failure through paracrine signals for hepatic ATM and STAT3 pathways. FASEB J. 35, e21471 (2021).","journal-title":"FASEB J."},{"key":"67102_CR23","doi-asserted-by":"publisher","DOI":"10.1111\/cpr.12829","volume":"53","author":"Y Wang","year":"2020","unstructured":"Wang, Y. et al. TNF-\u03b1\/HMGB1 inflammation signalling pathway regulates pyroptosis during liver failure and acute kidney injury. Cell Prolif. 53, e12829 (2020).","journal-title":"Cell Prolif."},{"key":"67102_CR24","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1016\/j.lfs.2019.05.061","volume":"230","author":"F-Z Jiao","year":"2019","unstructured":"Jiao, F.-Z. et al. Protective role of AGK2 on thioacetamide-induced acute liver failure in mice. Life Sci. 230, 68\u201375 (2019).","journal-title":"Life Sci."},{"issue":"7","key":"67102_CR25","doi-asserted-by":"publisher","first-page":"2135","DOI":"10.3390\/nu12072135","volume":"12","author":"AM Czarnecka","year":"2020","unstructured":"Czarnecka, A. M., Hilgier, W. & Zieli\u0144ska, M. S-Adenosylmethionine deficiency and brain accumulation of S-adenosylhomocysteine in thioacetamide-induced acute liver failure. Nutrients 12(7), 2135 (2020).","journal-title":"Nutrients"},{"key":"67102_CR26","doi-asserted-by":"publisher","first-page":"204173142312003","DOI":"10.1177\/20417314231200328","volume":"14","author":"Q Chen","year":"2023","unstructured":"Chen, Q. et al. Establishing an hTERT-driven immortalized umbilical cord-derived mesenchymal stem cell line and its therapeutic application in mice with liver failure. J. Tissue Eng 14, 20417314231200330 (2023).","journal-title":"J. Tissue Eng"},{"key":"67102_CR27","doi-asserted-by":"publisher","first-page":"1554","DOI":"10.1038\/aps.2017.54","volume":"38","author":"F Wang","year":"2017","unstructured":"Wang, F. et al. Acute liver failure enhances oral plasma exposure of zidovudine in rats by downregulation of hepatic UGT2B7 and intestinal P-gp. Acta Pharmacol. Sin. 38, 1554\u20131565 (2017).","journal-title":"Acta Pharmacol. Sin."},{"key":"67102_CR28","doi-asserted-by":"publisher","first-page":"1877","DOI":"10.1111\/liv.12731","volume":"35","author":"Y He","year":"2015","unstructured":"He, Y. et al. Mechanisms of fibrosis in acute liver failure. Liver Int. 35, 1877\u20131885 (2015).","journal-title":"Liver Int."},{"key":"67102_CR29","doi-asserted-by":"publisher","first-page":"3791","DOI":"10.1016\/j.apsb.2021.11.010","volume":"11","author":"H Qian","year":"2021","unstructured":"Qian, H. et al. Dual roles of p62\/SQSTM1 in the injury and recovery phases of acetaminophen-induced liver injury in mice. Acta Pharm. Sin. B 11, 3791\u20133805 (2021).","journal-title":"Acta Pharm. Sin. B"},{"key":"67102_CR30","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2019.116976","volume":"238","author":"Q Chen","year":"2019","unstructured":"Chen, Q., Wang, Y., Jiao, F. Z., Shi, C. X. & Gong, Z. J. Histone deacetylase 6 inhibitor ACY1215 offers a protective effect through the autophagy pathway in acute liver failure. Life Sci. 238, 116976 (2019).","journal-title":"Life Sci."},{"key":"67102_CR31","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2022.109121","volume":"717","author":"OA Ahmedy","year":"2022","unstructured":"Ahmedy, O. A., Salem, H. H., Sayed, N. H. & Ibrahim, S. M. Naringenin affords protection against lipopolysaccharide\/D-galactosamine-induced acute liver failure: Role of autophagy. Arch. Biochem Biophys. 717, 109121 (2022).","journal-title":"Arch. Biochem Biophys."},{"key":"67102_CR32","doi-asserted-by":"publisher","first-page":"728","DOI":"10.1016\/j.cell.2011.10.026","volume":"147","author":"N Mizushima","year":"2011","unstructured":"Mizushima, N. & Komatsu, M. Autophagy: renovation of cells and tissues. Cell 147, 728\u2013741 (2011).","journal-title":"Cell"},{"key":"67102_CR33","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1186\/s12964-018-0314-2","volume":"17","author":"H Lv","year":"2019","unstructured":"Lv, H. et al. Corilagin alleviates acetaminophen-induced hepatotoxicity via enhancing the AMPK\/GSK3\u03b2-Nrf2 signaling pathway. Cell Commun. Signal 17, 2 (2019).","journal-title":"Cell Commun. Signal"},{"key":"67102_CR34","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2023.115097","volume":"165","author":"L Zhu","year":"2023","unstructured":"Zhu, L. et al. Xanthohumol protect against acetaminophen-induced hepatotoxicity via Nrf2 activation through the AMPK\/Akt\/GSK3\u03b2 pathway. Biomed. Pharmacother. 165, 115097 (2023).","journal-title":"Biomed. Pharmacother."},{"key":"67102_CR35","doi-asserted-by":"publisher","first-page":"9282484","DOI":"10.1155\/2022\/9282484","volume":"2022","author":"C Zhu","year":"2022","unstructured":"Zhu, C. et al. Multiple roles of SIRT2 in regulating physiological and pathological signal transduction. Genet Res. (Camb) 2022, 9282484 (2022).","journal-title":"Genet Res. (Camb)"},{"key":"67102_CR36","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1111\/j.1474-9726.2007.00304.x","volume":"6","author":"F Wang","year":"2007","unstructured":"Wang, F., Nguyen, M., Qin, F. X. & Tong, Q. SIRT2 deacetylates FOXO3a in response to oxidative stress and caloric restriction. Aging Cell 6, 505\u2013514 (2007).","journal-title":"Aging Cell"},{"key":"67102_CR37","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1080\/15548627.2015.1023981","volume":"11","author":"J Zhang","year":"2015","unstructured":"Zhang, J. et al. Histone deacetylase inhibitors induce autophagy through FOXO1-dependent pathways. Autophagy 11, 629\u2013642 (2015).","journal-title":"Autophagy"},{"key":"67102_CR38","doi-asserted-by":"publisher","first-page":"1079962","DOI":"10.3389\/fimmu.2022.1079962","volume":"13","author":"A Gandhirajan","year":"2022","unstructured":"Gandhirajan, A. et al. SIRT2-PFKP interaction dysregulates phagocytosis in macrophages with acute ethanol-exposure. Front. Immunol. 13, 1079962 (2022).","journal-title":"Front. Immunol."},{"key":"67102_CR39","doi-asserted-by":"publisher","first-page":"791","DOI":"10.1186\/s12885-018-4710-1","volume":"18","author":"T Kozako","year":"2018","unstructured":"Kozako, T. et al. Novel small molecule SIRT2 inhibitors induce cell death in leukemic cell lines. BMC Cancer 18, 791 (2018).","journal-title":"BMC Cancer"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-67102-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-67102-w","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-67102-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,15]],"date-time":"2024-07-15T09:11:47Z","timestamp":1721034707000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-67102-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,15]]},"references-count":39,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["67102"],"URL":"https:\/\/doi.org\/10.1038\/s41598-024-67102-w","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,15]]},"assertion":[{"value":"23 January 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 July 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 July 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"16278"}}