{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T02:36:54Z","timestamp":1740105414958,"version":"3.37.3"},"reference-count":30,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2022,10,23]],"date-time":"2022-10-23T00:00:00Z","timestamp":1666483200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cell Biology International"],"published-print":{"date-parts":[[2023,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Cardiac hypertrophy caused by angiotensin II (Ang II) is essential for the pathological process of heart failure. The intermediate calcium\u2010activated potassium channel (SK4) has been shown to be involved in the process of the inflammatory response, cell proliferation, and apoptosis. However, the role of SK4 in cardiac hypertrophy has not been elucidated.\u00a0Cardiac hypertrophy in human\u2010induced pluripotent stem cells\u2010derived cardiomyocytes (HiPSC\u2010CMs) was induced by Ang II. Cells were transfected with SK4 adenovirus or treated with SK4 inhibitor (TRAM\u201034). TUNEL staining was used to assess the levels of apoptosis. Real\u2010time polymerase chain reaction and Western blot analysis were used to measure messenger RNA\u00a0(mRNA) and protein levels, respectively. The present results showed that SK4 expression was upregulated in HiPSC\u2010CMs stimulated by Ang II. The downregulation of SK4 by a specific inhibitor TRAM\u201034 markedly ameliorated cardiac hypertrophy (reflected by the mRNA levels of atrial natriuretic peptide, brain natriuretic peptide, and \u03b2\u2010myosin heavy chain)\u00a0and apoptosis (reflected by the level of Caspase 3, Bax, and Bcl\u20102) induced by Ang II treatment. The action of SK4 in cardiac hypertrophy was mediated by Ras\u2013Raf\u2013mitogen\u2010activated protein kinases 1\/2\u00a0(MEK1\/2)\u2013extracellular\u2010regulated protein kinases 1\/2 (ERK1\/2) and calcineurin (CN)\u2013nuclear factors of activated T cells (NFAT) activation. Our studies demonstrated that inhibition of SK4 significantly alleviated cardiac hypertrophy induced by Ang II in hiPSC\u2010CMs by targeting Ras\u2013Raf\u2013MEK1\/2\u2013ERK1\/2 signaling and CN\u2013NFAT signaling pathway. Our studies suggest that SK4 may serve as a potential therapeutic target that could delay hypertrophy.<\/jats:p>","DOI":"10.1002\/cbin.11948","type":"journal-article","created":{"date-parts":[[2022,10,23]],"date-time":"2022-10-23T19:14:43Z","timestamp":1666552483000},"page":"480-491","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Inhibition of intermittent calcium\u2010activated potassium channel (SK4) attenuates Ang II\u2010induced hypertrophy of human\u2010induced stem cell\u2010derived cardiomyocytes\u00a0via targeting Ras\u2013Raf\u2013MEK1\/2\u2013ERK1\/2 and CN\u2013NFAT signaling pathways"],"prefix":"10.1002","volume":"47","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0016-6329","authenticated-orcid":false,"given":"Hongyi","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Cardiology Renmin Hospital of Wuhan University Wuhan P. R. China"},{"name":"Cardiovascular Research Institute Wuhan University Wuhan P. R. China"},{"name":"Hubei Key Laboratory of Cardiology Wuhan P. R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xi","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Cardiology Renmin Hospital of Wuhan University Wuhan P. R. China"},{"name":"Cardiovascular Research Institute Wuhan University Wuhan P. R. China"},{"name":"Hubei Key Laboratory of Cardiology Wuhan P. R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanhong","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Cardiology Renmin Hospital of Wuhan University Wuhan P. R. China"},{"name":"Cardiovascular Research Institute Wuhan University Wuhan P. R. China"},{"name":"Hubei Key Laboratory of Cardiology Wuhan P. R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qingyan","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Cardiology Renmin Hospital of Wuhan University Wuhan P. R. China"},{"name":"Cardiovascular Research Institute Wuhan University Wuhan P. R. China"},{"name":"Hubei Key Laboratory of Cardiology Wuhan P. R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Congxin","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Cardiology Renmin Hospital of Wuhan University Wuhan P. R. China"},{"name":"Cardiovascular Research Institute Wuhan University Wuhan P. R. China"},{"name":"Hubei Key Laboratory of Cardiology Wuhan P. R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,10,23]]},"reference":[{"doi-asserted-by":"publisher","key":"e_1_2_10_2_1","DOI":"10.1007\/s00204-015-1607-5"},{"doi-asserted-by":"publisher","key":"e_1_2_10_3_1","DOI":"10.1177\/147323000703500609"},{"doi-asserted-by":"publisher","key":"e_1_2_10_4_1","DOI":"10.1016\/bs.apcsb.2015.11.007"},{"doi-asserted-by":"publisher","key":"e_1_2_10_5_1","DOI":"10.1152\/ajpheart.00775.2011"},{"doi-asserted-by":"publisher","key":"e_1_2_10_6_1","DOI":"10.1146\/annurev.physiol.65.092101.142243"},{"doi-asserted-by":"publisher","key":"e_1_2_10_7_1","DOI":"10.3390\/ijms20092164"},{"doi-asserted-by":"publisher","key":"e_1_2_10_8_1","DOI":"10.1098\/rstb.2005.1774"},{"doi-asserted-by":"publisher","key":"e_1_2_10_9_1","DOI":"10.15252\/emmm.201606937"},{"doi-asserted-by":"publisher","key":"e_1_2_10_10_1","DOI":"10.1161\/CIRCULATIONAHA.110.971721"},{"doi-asserted-by":"publisher","key":"e_1_2_10_11_1","DOI":"10.4061\/2011\/456815"},{"doi-asserted-by":"publisher","key":"e_1_2_10_12_1","DOI":"10.29828\/JFMA.200511.0004"},{"doi-asserted-by":"publisher","key":"e_1_2_10_13_1","DOI":"10.1152\/physrev.00021.2012"},{"doi-asserted-by":"publisher","key":"e_1_2_10_14_1","DOI":"10.1161\/01.CIR.102.4.470"},{"doi-asserted-by":"publisher","key":"e_1_2_10_15_1","DOI":"10.1016\/j.biocel.2009.08.002"},{"doi-asserted-by":"publisher","key":"e_1_2_10_16_1","DOI":"10.1152\/physiolgenomics.00224.2005"},{"doi-asserted-by":"publisher","key":"e_1_2_10_17_1","DOI":"10.1016\/j.cardiores.2005.06.020"},{"doi-asserted-by":"publisher","key":"e_1_2_10_18_1","DOI":"10.1074\/jbc.M206532200"},{"doi-asserted-by":"publisher","key":"e_1_2_10_19_1","DOI":"10.1002\/1878-0261.12087"},{"doi-asserted-by":"publisher","key":"e_1_2_10_20_1","DOI":"10.1007\/s00204-015-1477-x"},{"doi-asserted-by":"publisher","key":"e_1_2_10_21_1","DOI":"10.1172\/JCI30836"},{"doi-asserted-by":"publisher","key":"e_1_2_10_22_1","DOI":"10.1186\/1478-811X-12-8"},{"doi-asserted-by":"publisher","key":"e_1_2_10_23_1","DOI":"10.1038\/s41598-021-00422-3"},{"doi-asserted-by":"publisher","key":"e_1_2_10_24_1","DOI":"10.3389\/fphys.2020.590534"},{"doi-asserted-by":"publisher","key":"e_1_2_10_25_1","DOI":"10.1161\/01.RES.0000109415.17511.18"},{"doi-asserted-by":"publisher","key":"e_1_2_10_26_1","DOI":"10.1172\/JCI20317"},{"doi-asserted-by":"publisher","key":"e_1_2_10_27_1","DOI":"10.1007\/s10840-020-00736-8"},{"doi-asserted-by":"publisher","key":"e_1_2_10_28_1","DOI":"10.1016\/j.biopha.2020.110612"},{"doi-asserted-by":"publisher","key":"e_1_2_10_29_1","DOI":"10.3892\/mmr.2019.10591"},{"doi-asserted-by":"publisher","key":"e_1_2_10_30_1","DOI":"10.1007\/s00424-012-1165-0"},{"doi-asserted-by":"publisher","key":"e_1_2_10_31_1","DOI":"10.1152\/ajpheart.00110.2003"}],"container-title":["Cell Biology International"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cbin.11948","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cbin.11948","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cbin.11948","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,19]],"date-time":"2023-08-19T23:02:40Z","timestamp":1692486160000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cbin.11948"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,23]]},"references-count":30,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2023,2]]}},"alternative-id":["10.1002\/cbin.11948"],"URL":"https:\/\/doi.org\/10.1002\/cbin.11948","archive":["Portico"],"relation":{},"ISSN":["1065-6995","1095-8355"],"issn-type":[{"type":"print","value":"1065-6995"},{"type":"electronic","value":"1095-8355"}],"subject":[],"published":{"date-parts":[[2022,10,23]]},"assertion":[{"value":"2022-07-13","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-10-15","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-10-23","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}