Skip to main content
Journal cover image

Suppression of oxidative stress by β-hydroxybutyrate, an endogenous histone deacetylase inhibitor.

Publication ,  Journal Article
Shimazu, T; Hirschey, MD; Newman, J; He, W; Shirakawa, K; Le Moan, N; Grueter, CA; Lim, H; Saunders, LR; Stevens, RD; Newgard, CB; Farese, RV ...
Published in: Science
January 11, 2013

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-β-hydroxybutyrate (βOHB) is an endogenous and specific inhibitor of class I histone deacetylases (HDACs). Administration of exogenous βOHB, or fasting or calorie restriction, two conditions associated with increased βOHB abundance, all increased global histone acetylation in mouse tissues. Inhibition of HDAC by βOHB was correlated with global changes in transcription, including that of the genes encoding oxidative stress resistance factors FOXO3A and MT2. Treatment of cells with βOHB 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 βOHB conferred substantial protection against oxidative stress.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Science

DOI

EISSN

1095-9203

Publication Date

January 11, 2013

Volume

339

Issue

6116

Start / End Page

211 / 214

Location

United States

Related Subject Headings

  • Transcriptional Activation
  • Transcription, Genetic
  • Superoxide Dismutase
  • RNA, Small Interfering
  • Promoter Regions, Genetic
  • Oxidative Stress
  • Mice, Inbred C57BL
  • Mice
  • Metallothionein
  • Lipid Peroxidation
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Shimazu, T., Hirschey, M. D., Newman, J., He, W., Shirakawa, K., Le Moan, N., … Verdin, E. (2013). Suppression of oxidative stress by β-hydroxybutyrate, an endogenous histone deacetylase inhibitor. Science, 339(6116), 211–214. https://doi.org/10.1126/science.1227166
Shimazu, Tadahiro, Matthew D. Hirschey, John Newman, Wenjuan He, Kotaro Shirakawa, Natacha Le Moan, Carrie A. Grueter, et al. “Suppression of oxidative stress by β-hydroxybutyrate, an endogenous histone deacetylase inhibitor.Science 339, no. 6116 (January 11, 2013): 211–14. https://doi.org/10.1126/science.1227166.
Shimazu T, Hirschey MD, Newman J, He W, Shirakawa K, Le Moan N, et al. Suppression of oxidative stress by β-hydroxybutyrate, an endogenous histone deacetylase inhibitor. Science. 2013 Jan 11;339(6116):211–4.
Shimazu, Tadahiro, et al. “Suppression of oxidative stress by β-hydroxybutyrate, an endogenous histone deacetylase inhibitor.Science, vol. 339, no. 6116, Jan. 2013, pp. 211–14. Pubmed, doi:10.1126/science.1227166.
Shimazu T, Hirschey MD, Newman J, He W, Shirakawa K, Le Moan N, Grueter CA, Lim H, Saunders LR, Stevens RD, Newgard CB, Farese RV, de Cabo R, Ulrich S, Akassoglou K, Verdin E. Suppression of oxidative stress by β-hydroxybutyrate, an endogenous histone deacetylase inhibitor. Science. 2013 Jan 11;339(6116):211–214.
Journal cover image

Published In

Science

DOI

EISSN

1095-9203

Publication Date

January 11, 2013

Volume

339

Issue

6116

Start / End Page

211 / 214

Location

United States

Related Subject Headings

  • Transcriptional Activation
  • Transcription, Genetic
  • Superoxide Dismutase
  • RNA, Small Interfering
  • Promoter Regions, Genetic
  • Oxidative Stress
  • Mice, Inbred C57BL
  • Mice
  • Metallothionein
  • Lipid Peroxidation