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.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3735349 | PMC |
| http://dx.doi.org/10.1126/science.1227166 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Feeding nursery pigs diets containing peroxidized soybean oil has minimal effects on oxidative status but dramatically reduces serum vitamin E concentrations.
J Anim Sci
January 2025
USDA-ARS National Laboratory for Agriculture and the Environment, Ames, IA 50011, USA.
A subgroup of pigs from two experiments (EXP) were selected to evaluate the impact of pigs fed diets containing peroxidized soybean oil (SO) on plasma-based measures of oxidative stress and vitamin E. Pigs were fed diets containing SO that was either unprocessed (23 °C; peroxide value of 3 meq/kg and an anisidine value of 4) or thermally processed at 135 °C for 42 h (peroxide value of 30 meq/kg and an anisidine value of 501). The corn-soybean meal-based diets contained either 10% SO (EXP 1) or 8% SO (EXP 2).
View Article and Find Full Text PDFCardiotoxicity Associated With a Low Doses of 5-FU Promotes Morphoquantitative Changes in the Intrinsic Cardiac Nervous System.
Cardiovasc Toxicol
January 2025
Department of Morphological Sciences, State University of Maringa, Maringa, Parana, Brazil.
5-Fluorouracil (5-FU) is a chemotherapeutic that is used to treat solid tumors. However, 5-FU is associated with several side effects, including cardiotoxicity. Considering the importance of the intrinsic cardiac nervous system (ICNS) for the heart and that little is known about effects of 5-FU on this nervous system plexus, the purpose of the present study was to evaluate effects 5-FU at a low dose on the ICNS and oxidative and inflammatory effects in the heart in Wistar rats.
View Article and Find Full Text PDFDihydromyricetin Protects Against Hypoxia/Reoxygenation Injury in Cardiomyocytes by Activating miR-34a-Mediated Notch1 Pathway.
Cardiovasc Toxicol
January 2025
The Second Department of Cardiovascular Medicine, Baoji People's Hospital, Baoji, China.
Dihydromyricetin (Dih), a naturally occurring flavonoid, has been identified to exert a protective effect against ischemia/reperfusion injury. However, the detailed mechanisms remain unclear. Here we investigated the biological role of Dih in preventing hypoxia/reoxygenation (H/R) injury in cardiomyocytes.
View Article and Find Full Text PDFFluoride-induced testicular and ovarian toxicity: evidence from animal studies.
Biol Res
January 2025
Clinical Research Development Unit of Tabriz Valiasr Hospital, Tabriz University of Medical Sciences, Tabriz, Iran.
Fluoride (F), as a natural element found in a wide range of sources such as water and certain foods, has been proven to be beneficial in preventing dental caries, but concerns have been raised regarding its potential deleterious effects on overall health. Sodium fluoride (NaF), another form of F, has the ability to accumulate in reproductive organs and interfere with hormonal regulation and oxidative stress pathways, contributing to reproductive toxicity. While the exact mechanisms of F-induced reproductive toxicity are not fully understood, this review aims to elucidate the mechanisms involved in testicular and ovarian injury.
View Article and Find Full Text PDFMitochondrial Dysfunction in HFpEF: Potential Interventions Through Exercise.
J Cardiovasc Transl Res
January 2025
Cardiac Regeneration and Ageing Lab, Institute of Geriatrics (Shanghai University), Affiliated Nantong Hospital of Shanghai University (The Sixth People's Hospital of Nantong), School of Medicine, Shanghai University, Nantong, 226011, China.
HFpEF is a prevalent and complex type of heart failure. The concurrent presence of conditions such as obesity, hypertension, hyperglycemia, and hyperlipidemia significantly increase the risk of developing HFpEF. Mitochondria, often referred to as the powerhouses of the cell, are crucial in maintaining cellular functions, including ATP production, intracellular Ca regulation, reactive oxygen species generation and clearance, and the regulation of apoptosis.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!