{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T15:32:18Z","timestamp":1773675138725,"version":"3.50.1"},"reference-count":42,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2019,7,27]],"date-time":"2019-07-27T00:00:00Z","timestamp":1564185600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31571173"],"award-info":[{"award-number":["31571173"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31771290"],"award-info":[{"award-number":["31771290"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81401041"],"award-info":[{"award-number":["81401041"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81702454"],"award-info":[{"award-number":["81702454"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Acta Physiologica"],"published-print":{"date-parts":[[2020,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aim<\/jats:title><jats:p>Cardiac hypertrophy and myocardial apoptosis are two major factors in heart failure. As a classical regulator of apoptosis, apoptosis repressor with caspase recruitment domain (ARC) has recently also been found to have a protective effect against hypertrophy. However, the mechanism underlying this effect is still not fully understood.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In the present study, we established animal and cellular models to monitor the changes in total and nuclear ARC during cardiac hypertrophic processes. The preventive effects of nuclear ARC in cellular hypertrophy were verified by ARC regulation and nuclear export inhibition. To further explore the mechanism for nuclear ARC superficially, we analysed proteins that interact with ARC in the nucleus via Co\u2010IP and mass spectrometry.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The expression of total ARC in hypertrophic myocardial tissue and H9C2 cells remained invariant, while the level of nuclear ARC decreased dramatically. By altering the content of ARC in H9C2 cells, we found that both nuclear ARC transfection and nuclear ARC export blockade attenuated norepinephrine or angiotensin II\u2010induced hypertrophy, while ARC knockdown had an inverse effect. Co\u2010IP data showed that ARC interacted with prohibitin (PHB) in the nucleus and might participate in maintaining the level of PHB in cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These findings suggest a novel mechanism for ARC in cardiac hypertrophy prevention and also indicate that the anti\u2010hypertrophic roles of ARC are probably associated with its localization in nucleus, which imply the nuclear ARC as a potential therapeutic target for cardiac hypertrophy.<\/jats:p><\/jats:sec>","DOI":"10.1111\/apha.13337","type":"journal-article","created":{"date-parts":[[2019,7,1]],"date-time":"2019-07-01T07:44:55Z","timestamp":1561967095000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Loss of nuclear ARC contributes to the development of cardiac hypertrophy in rats"],"prefix":"10.1111","volume":"228","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6573-035X","authenticated-orcid":false,"given":"Fang","family":"Xie","sequence":"first","affiliation":[{"name":"Department of Military Cognitive and Stress Medicine, Institute of Military Cognitive and Brain Sciences Academy of Military Medical Sciences Beijing P.R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhu\u2010Song","family":"Mei","sequence":"additional","affiliation":[{"name":"Department of Military Cognitive and Stress Medicine, Institute of Military Cognitive and Brain Sciences Academy of Military Medical Sciences Beijing P.R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xue","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Military Cognitive and Stress Medicine, Institute of Military Cognitive and Brain Sciences Academy of Military Medical Sciences Beijing P.R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Military Cognitive and Stress Medicine, Institute of Military Cognitive and Brain Sciences Academy of Military Medical Sciences Beijing P.R. China"},{"name":"Shandong University of Traditional Chinese Medicine Jinan P.R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yun","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Military Cognitive and Stress Medicine, Institute of Military Cognitive and Brain Sciences Academy of Military Medical Sciences Beijing P.R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shi\u2010Da","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Military Cognitive and Stress Medicine, Institute of Military Cognitive and Brain Sciences Academy of Military Medical Sciences Beijing P.R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ling\u2010Jia","family":"Qian","sequence":"additional","affiliation":[{"name":"Department of Military Cognitive and Stress Medicine, Institute of Military Cognitive and Brain Sciences Academy of Military Medical Sciences Beijing P.R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,7,27]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature06798"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000148632.35500.d9"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10741-016-9536-9"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13344"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1161\/hc0402.102863"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1161\/hh1501.094115"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.88.3.298"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2017.7047"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.9.5156"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M400695200"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1582-4934.2010.01221.x"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M104080200"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-008-0434-z"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.107.750869"},{"issue":"8","key":"e_1_2_8_16_1","first-page":"928","article-title":"Interplay of phosphorylated apoptosis repressor with CARD, Casein kinase\u20102 and reactive oxygen species in regulating endothelin\u20101\u2010induced cardiomyocyte hypertrophy","volume":"16","author":"Murtaza I","year":"2013","journal-title":"Iran J Basic Med Sci"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M706466200"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11010-016-2870-3"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10495-007-0094-4"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2014.430"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.442061"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2015.41"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.85.12.e70"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1016959108"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.105.576785"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehv713"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.111.034512"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1213\/ANE.0b013e318205689b"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M609046200"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.114892"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M609186200"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0710017104"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2005.03.040"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12964-017-0170-5"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.2174\/157340311799960618"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12192-008-0086-5"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.3109\/10715762.2014.991724"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1159\/000443370"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chembiol.2013.02.006"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M605260200"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.carpath.2014.05.003"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12192-013-0416-0"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(02)00600-7"}],"container-title":["Acta Physiologica"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fapha.13337","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/apha.13337","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/apha.13337","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/apha.13337","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,8]],"date-time":"2023-09-08T00:29:11Z","timestamp":1694132951000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/apha.13337"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,7,27]]},"references-count":42,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2020,2]]}},"alternative-id":["10.1111\/apha.13337"],"URL":"https:\/\/doi.org\/10.1111\/apha.13337","archive":["Portico"],"relation":{},"ISSN":["1748-1708","1748-1716"],"issn-type":[{"value":"1748-1708","type":"print"},{"value":"1748-1716","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,7,27]]},"assertion":[{"value":"2019-02-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-06-22","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-07-27","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e13337"}}