We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
The dietary compound curcumin inhibits p300 histone acetyltransferase activity and prevents heart failure in rats.
- Authors
Morimoto, Tatsuya; Sunagawa, Yoichi; Kawamura, Teruhisa; Takaya, Tomohide; Wada, Hiromichi; Nagasawa, Atsushi; Komeda, Masashi; Fujita, Masatoshi; Shimatsu, Akira; Kita, Toru; Hasegawa, Koji
- Abstract
Hemodynamic overload in the heart can trigger maladaptive hypertrophy of cardiomyocytes. A key signaling event in this process is nuclear acetylation by histone deacetylases and p300, an intrinsic histone acetyltransferase (HAT). It has been previously shown that curcumin, a polyphenol responsible for the yellow color of the spice turmeric, possesses HAT inhibitory activity with specificity for the p300/CREB-binding protein. We found that curcumin inhibited the hypertrophy-induced acetylation and DNA-binding abilities of GATA4, a hypertrophy-responsive transcription factor, in rat cardiomyocytes. Curcumin also disrupted the p300/GATA4 complex and repressed agonist- and p300-induced hypertrophic responses in these cells. Both the acetylated form of GATA4 and the relative levels of the p300/GATA4 complex markedly increased in rat hypertensive hearts in vivo. The effects of curcumin were examined in vivo in 2 different heart failure models: hypertensive heart disease in salt-sensitive Dahl rats and surgically induced myocardial infarction in rats. In both models, curcumin prevented deterioration of systolic function and heart failure-induced increases in both myocardial wall thickness and diameter. From these results, we conclude that inhibition of p300 HAT activity by the nontoxic dietary compound curcumin may provide a novel therapeutic strategy for heart failure in humans.
- Publication
The Journal of clinical investigation, 2008, Vol 118, Issue 3, p868
- ISSN
0021-9738
- Publication type
Journal Article
- DOI
10.1172/JCI33160