Tadahiro Shimazu1,2, Matthew D. Hirschey1,2, John C. Newman1,2, Wenjuan He1,2, Kotaro Shirakawa1,2, Natacha Le Moan3, Carrie A. Grueter4,5, Hyungwook Lim1,2, Laura R. Saunders1,2, Robert Stevens6, Christopher B. Newgard6, Robert V. Farese4,1,5, Rafael de Cabo7, Scott M. Ulrich8, Katerina Akassoglou3, Eric Verdin1,2
1Department of Medicine, University of California, San Francisco, CA 94143, USA
2Gladstone Institute of Virology and Immunology, San Francisco, CA 94158, USA
3Gladstone Institute of Neurological Disease, San Francisco, CA 94158, USA
4Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94143, USA
5Gladstone Institute of Cardiovascular Disease, San Francisco, CA 94158, USA
6Sarah W. Stedman Nutrition and Metabolism Center, and Departments of Pharmacology and Cancer Biology and Medicine, Duke University Medical Center, Durham, NC 27704, USA.
7Laboratory of Experimental Gerontology, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA
8Department of Chemistry, Ithaca College, Ithaca, NY 14850, USA
Tóm tắt
Stress Protector
During prolonged fasting, the oxidation of fatty acids leads to increased accumulation of
d
-β-hydroxybutyrate (βOHB) in the bloodstream. Such increased concentrations of βOHB inhibit class I histone deacetylases. Histone acetylation in turn influences transcriptional activity at various genes.
Shimazu
et al.
(p.
211
, published online 6 December; see the Perspective by
Sassone-Corsi
) found that among the genes showing increased transcription in animals treated with high concentrations of βOHB were two genes implicated in cellular responses to oxidative stress. When treated ahead of time with βOHB, mice were protected from the toxic effects of the oxidative stress causing poison paraquat.
