| First Author | Kuno A | Year | 2013 |
| Journal | J Biol Chem | Volume | 288 |
| Issue | 8 | Pages | 5963-72 |
| PubMed ID | 23297412 | Mgi Jnum | J:196087 |
| Mgi Id | MGI:5486535 | Doi | 10.1074/jbc.M112.392050 |
| Citation | Kuno A, et al. (2013) Resveratrol improves cardiomyopathy in dystrophin-deficient mice through SIRT1 protein-mediated modulation of p300 protein. J Biol Chem 288(8):5963-72 |
| abstractText | Cardiomyopathy is the main cause of death in Duchenne muscular dystrophy. Here, we show that oral administration of resveratrol, which leads to activation of an NAD(+)-dependent protein deacetylase SIRT1, suppresses cardiac hypertrophy and fibrosis and restores cardiac diastolic function in dystrophin-deficient mdx mice. The pro-hypertrophic co-activator p300 protein but not p300 mRNA was up-regulated in the mdx heart, and resveratrol administration down-regulated the p300 protein level. In cultured cardiomyocytes, cardiomyocyte hypertrophy induced by the alpha(1)-agonist phenylephrine was inhibited by the overexpression of SIRT1 as well as resveratrol, both of which down-regulated p300 protein levels but not p300 mRNA levels. In addition, activation of atrial natriuretic peptide promoter by p300 was inhibited by SIRT1. We found that SIRT1 induced p300 down-regulation via the ubiquitin-proteasome pathway by deacetylation of lysine residues for ubiquitination. These findings indicate the pathological significance of p300 up-regulation in the dystrophic heart and indicate that SIRT1 activation has therapeutic potential for dystrophic cardiomyopathy. |
