Suppression of oxidative stress by [beta]-hydroxybutyrate, an endogenous histone deacetylase inhibitor

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From: Science(Vol. 339, Issue 6116)
Publisher: American Association for the Advancement of Science
Document Type: Author abstract; Report
Length: 135 words

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Abstract :

Concentrations of acetyl-coenzyme A and nicotinamide adenine dinucleotide ([NAD.sup.+]) affect histone acetyiation and thereby couple cellular metabolic status and transcriptional regulation. We report that the ketone body D-[beta]-hydroxybutyrate ([beta]OHB) is an endogenous and specific inhibitor of class I histone deacetylases (HDACs). Administration of exogenous [beta]OHB, or fasting or calorie restriction, two conditions associated with increased [beta]OHB abundance, all increased global histone acetylation in mouse tissues. Inhibition of HDAC by [beta]OHB was correlated with global changes in transcription, including that of the genes encoding oxidative stress resistance factors FOXO3A and MT2. Treatment of ceus with [beta]OHB 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 [beta]OHB conferred substantial protection against oxidative stress. 10.1126/science.1227166

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Gale Document Number: GALE|A316938805