The Polyunsaturated Fatty Acids EPA and DHA Prevent Myocardial Infarction-induced Heart Failure by Inhibiting p300-HAT Activity in Rats

Sunagawa, Yoichi; Katayama, Ayumi; Funamoto, Masafumi; Shimizu, Kana; Shimizu, Satoshi; Miyazaki, Yusuke; Hasegawa, Koji; Morimoto, Tatsuya

doi:10.15420/ecr.2021.16.po12

Cited by 1 publication

(1 citation statement)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Quercetin and butyric acid inhibit cancer cell growth [10,11], whereas curcumin and resveratrol suppress the development of heart failure [12,13]. In addition, several compounds and natural products, such as metformin, n-3 PUFA (DHA, EPA), anacardic acid, and curcumin (CUR), suppress cardiomyocyte hypertrophy by inhibiting p300-HAT activity [5,[14][15][16]. CUR, a polyphenol derived from turmeric (Curcuma longa) in the ginger family, has a p300-specific inhibitory effect on HAT activity [17].…”

Section: Introductionmentioning

confidence: 99%

Pyrazole-Curcumin Suppresses Cardiomyocyte Hypertrophy by Disrupting the CDK9/CyclinT1 Complex

et al. 2022

Self Cite

View full text Add to dashboard Cite

The intrinsic histone acetyltransferase (HAT), p300, has an important role in the development and progression of heart failure. Curcumin (CUR), a natural p300-specific HAT inhibitor, suppresses hypertrophic responses and prevents deterioration of left-ventricular systolic function in heart-failure models. However, few structure–activity relationship studies on cardiomyocyte hypertrophy using CUR have been conducted. To evaluate if prenylated pyrazolo curcumin (PPC) and curcumin pyrazole (PyrC) can suppress cardiomyocyte hypertrophy, cultured cardiomyocytes were treated with CUR, PPC, or PyrC and then stimulated with phenylephrine (PE). PE-induced cardiomyocyte hypertrophy was inhibited by PyrC but not PPC at a lower concentration than CUR. Western blotting showed that PyrC suppressed PE-induced histone acetylation. However, an in vitro HAT assay showed that PyrC did not directly inhibit p300-HAT activity. As Cdk9 phosphorylates both RNA polymerase II and p300 and increases p300-HAT activity, the effects of CUR and PyrC on the kinase activity of Cdk9 were examined. Phosphorylation of p300 by Cdk9 was suppressed by PyrC. Immunoprecipitation-WB showed that PyrC inhibits Cdk9 binding to CyclinT1 in cultured cardiomyocytes. PyrC may prevent cardiomyocyte hypertrophic responses by indirectly suppressing both p300-HAT activity and RNA polymerase II transcription elongation activity via inhibition of Cdk9 kinase activity.

show abstract