| First Author | Shimazu T | Year | 2013 |
| Journal | Science | Volume | 339 |
| Issue | 6116 | Pages | 211-4 |
| PubMed ID | 23223453 | Mgi Jnum | J:192550 |
| Mgi Id | MGI:5465366 | Doi | 10.1126/science.1227166 |
| Citation | Shimazu T, et al. (2013) Suppression of oxidative stress by beta-hydroxybutyrate, an endogenous histone deacetylase inhibitor. Science 339(6116):211-4 |
| abstractText | Concentrations of acetyl-coenzyme A and nicotinamide adenine dinucleotide (NAD(+)) affect histone acetylation and thereby couple cellular metabolic status and transcriptional regulation. We report that the ketone body d-beta-hydroxybutyrate (betaOHB) is an endogenous and specific inhibitor of class I histone deacetylases (HDACs). Administration of exogenous betaOHB, or fasting or calorie restriction, two conditions associated with increased betaOHB abundance, all increased global histone acetylation in mouse tissues. Inhibition of HDAC by betaOHB was correlated with global changes in transcription, including that of the genes encoding oxidative stress resistance factors FOXO3A and MT2. Treatment of cells with betaOHB increased histone acetylation at the Foxo3a and Mt2 promoters, and both genes were activated by selective depletion of HDAC1 and HDAC2. Consistent with increased FOXO3A and MT2 activity, treatment of mice with betaOHB conferred substantial protection against oxidative stress. |
