{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,12]],"date-time":"2026-04-12T06:44:24Z","timestamp":1775976264997,"version":"3.50.1"},"reference-count":32,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2025,8,28]],"date-time":"2025-08-28T00:00:00Z","timestamp":1756339200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,8,28]],"date-time":"2025-08-28T00:00:00Z","timestamp":1756339200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Biochem &amp;amp; Molecular Tox"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Ankyrin2 (ANK2) has been found to be abnormally overexpressed in myocardial infarction (MI) cell models, but its role and related mechanisms in MI progression have not been explored. Cardiomyocytes (AC16) were subjected to hypoxia\/reoxygenation (H\/R) treatment to mimic MI cell models, and ischemia\/reperfusion (I\/R)\u2010induced myocardial injury was used to establish MI rat models. Cell viability, apoptosis and mitochondrial membrane potential (MMP) depolarization were analyzed by CCK8 assay, flow cytometry and JC\u20101 staining. The levels of inflammatory\u2010related factors and ferroptosis\u2010related markers were determined by commercial kits. ANK2 and ubiquitin\u2010specific peptidase 46 (USP46) protein levels were analyzed using western blot. Cycloheximide treatment assay and ubiquitination assay were used to confirm the regulation of USP46 on ANK2 protein stability and ubiquitination level. After H\/R treatment, AC16 cell viability was reduced, while apoptosis, inflammation and ferroptosis were enhanced. ANK2 was upregulated in H\/R\u2010induced AC16 cells, and its knockdown repressed H\/R\u2010induced cardiomyocyte apoptosis, inflammation and ferroptosis. USP46 enhanced ANK2 protein stability and expression by deubiquitination. Overexpression of ANK2 also reversed the inhibition effect of USP46 knockdown on H\/R\u2010induced cardiomyocyte injury. In addition, downregulation of USP46 alleviated myocardial injury in I\/R\u2010induced rat models by decreasing ANK2 expression. USP46\u2010stabilized ANK2 promoted cardiomyocyte apoptosis, inflammation and ferroptosis to aggravate MI process.<\/jats:p>","DOI":"10.1002\/jbt.70454","type":"journal-article","created":{"date-parts":[[2025,8,29]],"date-time":"2025-08-29T06:00:25Z","timestamp":1756447225000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Inhibition of USP46\/ANK2 Axis Alleviates Myocardial Infarction in Hypoxia\/Reoxygenation\u2010Treated Cardiomyocytes and Ischemia\/Reperfusion\u2010Induced Rat Models"],"prefix":"10.1002","volume":"39","author":[{"given":"Zhong","family":"Xie","sequence":"first","affiliation":[{"name":"Department of Cardiology, the First Affiliated Hospital, Hengyang Medical School University of South China Hengyang City Hunan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiming","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Cardiology, the First Affiliated Hospital, Hengyang Medical School University of South China Hengyang City Hunan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dan","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Cardiology, the First Affiliated Hospital, Hengyang Medical School University of South China Hengyang City Hunan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Cardiology, the First Affiliated Hospital, Hengyang Medical School University of South China Hengyang City Hunan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-5987-4510","authenticated-orcid":false,"given":"Junbi","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Cardiology, the First Affiliated Hospital, Hengyang Medical School University of South China Hengyang City Hunan China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,8,28]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12872-023-03231-w"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2022.103968"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mayocp.2019.05.001"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000000757"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/2211-5463.13276"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2023.1252942"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10495-022-01785-2"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1155\/2021\/9929687"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12890-022-02279-2"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2023.104818"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2023.112784"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40246-024-00644-2"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-39203-z"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddad081"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcvm.2022.850991"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1177\/11779322241285982"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-41836-z"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-41843-0"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2023.167011"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2020.112188"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1097\/SHK.0000000000002401"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2022.113751"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40119-023-00339-0"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1159\/000308821"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2022.03.058"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12013-024-01528-x"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1177\/15353702231191186"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3739"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2023.09.001"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1004822"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.13194"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/cbin.11937"}],"container-title":["Journal of Biochemical and Molecular Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jbt.70454","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jbt.70454","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jbt.70454","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,12]],"date-time":"2026-04-12T05:57:59Z","timestamp":1775973479000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jbt.70454"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,28]]},"references-count":32,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2025,9]]}},"alternative-id":["10.1002\/jbt.70454"],"URL":"https:\/\/doi.org\/10.1002\/jbt.70454","archive":["Portico"],"relation":{},"ISSN":["1095-6670","1099-0461"],"issn-type":[{"value":"1095-6670","type":"print"},{"value":"1099-0461","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,28]]},"assertion":[{"value":"2025-04-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-11","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-28","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70454"}}