{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T19:21:05Z","timestamp":1767986465178,"version":"3.49.0"},"reference-count":34,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2021,12,16]],"date-time":"2021-12-16T00:00:00Z","timestamp":1639612800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82060046"],"award-info":[{"award-number":["82060046"]}],"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":["81560040"],"award-info":[{"award-number":["81560040"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Cardiac hypertrophy is a complex process induced by the activation of multiple signaling pathways. We previously reported that anacardic acid (AA), a histone acetyltransferase (HAT) inhibitor, attenuates phenylephrine (PE)-induced cardiac hypertrophy by downregulating histone H3 acetylation at lysine 9 (H3K9ac). Unfortunately, the related upstream signaling events remained unknown. The mitogen-activated protein kinase (MAPK) pathway is an important regulator of cardiac hypertrophy. In this study, we explored the role of JNK\/MAPK signaling pathway in cardiac hypertrophy induced by PE. The mice cardiomyocyte hypertrophy model was successfully established by treating cells with PE<jats:italic>in vitro<\/jats:italic>. This study showed that p-JNK directly interacts with HATs (P300 and P300\/CBP-associated factor, PCAF) and alters H3K9ac. In addition, both the JNK inhibitor SP600125 and the HAT inhibitor AA attenuated p-JNK overexpression and H3K9ac hyperacetylation by inhibiting P300 and PCAF during PE-induced cardiomyocyte hypertrophy. Moreover, we demonstrated that both SP600125 and AA attenuate the overexpression of cardiac hypertrophy-related genes (<jats:italic>MEF2A<\/jats:italic>,<jats:italic>ANP<\/jats:italic>,<jats:italic>BNP<\/jats:italic>, and<jats:italic>\u03b2-MHC<\/jats:italic>), preventing cardiomyocyte hypertrophy and dysfunction. These results revealed a novel mechanism through which AA might protect mice from PE-induced cardiomyocyte hypertrophy. In particular, AA inhibits the effects of JNK signaling on HATs-mediated histone acetylation, and could therefore be used to prevent and treat pathological cardiac hypertrophy.<\/jats:p>","DOI":"10.1371\/journal.pone.0261388","type":"journal-article","created":{"date-parts":[[2021,12,16]],"date-time":"2021-12-16T18:40:03Z","timestamp":1639680003000},"page":"e0261388","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":10,"title":["JNK signaling-dependent regulation of histone acetylation are involved in anacardic acid alleviates cardiomyocyte hypertrophy induced by phenylephrine"],"prefix":"10.1371","volume":"16","author":[{"given":"Bohui","family":"Peng","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chang","family":"Peng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaomei","family":"Luo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7355-8337","authenticated-orcid":true,"given":"Shuqi","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qian","family":"Mao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huanting","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao","family":"Han","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2021,12,16]]},"reference":[{"key":"pone.0261388.ref001","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1038\/s41569-018-0007-y","article-title":"Mechanisms of physiological and pathological cardiac hypertrophy.","volume":"15","author":"M Nakamura","year":"2018","journal-title":"Nat Rev Cardiol"},{"key":"pone.0261388.ref002","doi-asserted-by":"crossref","first-page":"e11297","DOI":"10.15252\/emmm.201911297","article-title":"Targeting cardiac hypertrophy through a nuclear co-repressor","volume":"11","author":"A Grund","year":"2019","journal-title":"EMBO Mol Med"},{"key":"pone.0261388.ref003","doi-asserted-by":"crossref","first-page":"2065","DOI":"10.4155\/fmc.15.132","article-title":"JNK pathway signaling: a novel and smarter therapeutic targets for various biological diseases.","volume":"7","author":"A Kumar","year":"2015","journal-title":"Future Med Chem"},{"key":"pone.0261388.ref004","doi-asserted-by":"crossref","first-page":"6354","DOI":"10.1038\/s41598-019-42936-x","article-title":"The TIR\/BB-loop mimetic AS-1 prevents Ang II-induced hypertensive cardiac hypertrophy via NF-\u03baB dependent downregulation of miRNA-143.","volume":"9","author":"J Song","year":"2019","journal-title":"Sci Rep."},{"key":"pone.0261388.ref005","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1161\/CIRCRESAHA.118.313854","article-title":"ATF6 Regulates Cardiac Hypertrophy by Transcriptional Induction of the mTORC1 Activator","volume":"124","author":"EA Blackwood","year":"2019","journal-title":"Rheb. 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