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We previously reported that anacardic acid (AA), a histone acetylase (HAT) inhibitor, attenuates phenylephrine (PE)-induced cardiac hypertrophy by downregulating histone H3 acetylation at lysine 9 (H3K9ac). Unfortunately, the 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 in cardiac hypertrophy. A mouse model of cardiomyocyte hypertrophy was successfully established in vitro using PE. 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 H3K9 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 (MEF2A, ANP, BNP, and β-MHC), preventing cardiomyocyte hypertrophy and dysfunction. These results revealed a novel mechanism through which AA might protect mice from PE-induced cardiac hypertrophy. In particular, AA inhibits the effects of JNK signaling on HAT-mediated histone acetylation, and could therefore be used to prevent and treat hypertrophic cardiomyopathy.AAanacardic acidANPatrial natriuretic peptideBNPbrain natriuretic peptideCoIPCo-immunoprecipitationHAThistone acetyltransferaseHDAChistone deacetylaseH3K9histone H3 lysine 9H3K9acacetylated lysine 9 on histone H3JNKc-Jun N-terminal KinasePCAFP300/CBP-associated factorPEphenylephrine.", "digital" : true, "printed" : null, "sourceYear" : 2020, "foreignEdition" : null, "foreignLanguage" : true, "fullPublication" : false, "conferencePublication" : false, "nationalOrigin" : false, "missingAuthor" : false, "oaType" : "NONE", "oaCheckDate" : "2024-03-08", "oaFree" : false, "citationCount" : 0, "citationCountUnpublished" : 0, "citationCountWoOther" : 0, "independentCitCountWoOther" : 0, "doiCitationCount" : 0, "wosCitationCount" : 0, "scopusCitationCount" : 0, "independentCitationCount" : 0, "unhandledCitationCount" : 0, "citingPubCount" : 0, "independentCitingPubCount" : 0, "unhandledCitingPubCount" : 0, "citedPubCount" : 1, "citedCount" : 1, "hasCitationDuplums" : false, "userChangeableUntil" : "2020-05-14T20:43:55.941+0000", "directInstitutesForSort" : "", "ownerAuthorCount" : 14, "ownerInstituteCount" : 27, "directInstituteCount" : 0, "authorCount" : 7, "contributorCount" : 0, "hasQualityFactor" : false, "link" : "/api/publication/31178197", "label" : "Peng Bohui et al. 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