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Acetate supplementation increases brain histone acetylation and inhibits histone deacetylase activity and expression

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Abstract

Acetate supplementation increases brain, heart, and liver acetyl-CoA levels and reduces lipopolysaccharide-induced neuroinflammation. Because intracellular acetyl-CoA can be used to alter histone acetylation-state, using Western blot analysis, we measured the temporal effect that acetate supplementation had on brain and liver histone acetylation following a single oral dose of glyceryl triacetate (6 g/kg). In parallel experiments, we measured the effect that acetate supplementation had on histone deacetylase (HDAC) and histone acetyltransferase (HAT) enzymic activities and the expression levels of HDAC class I and II enzymes using Western blot analysis. We found that acetate supplementation increased the acetylation-state of brain histone H4 at lysine 8 at 2 and 4 h, histone H4 at lysine 16 at 4 and 24 h, and histone H3 at lysine 9 at 4 h following treatment. No changes in other forms of brain or liver H3 and H4 acetylation-state were found at any post-treatment times measured. Enzymic HAT and HDAC assays on brain extracts showed that acetate supplementation had no effect on HAT activity, but significantly inhibited by 2-fold HDAC activity at 2 and 4 h post-treatment. Western blot analysis demonstrated that HDAC 2 levels were decreased at 4 h following treatment. Based on these results, we conclude that acetyl-CoA derived from acetate supplementation increases brain histone acetylation-state by reducing HDAC activity and expression.

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Acknowledgments

This publication was made possible by a Grant from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH) (# P20RR17699-05). We would also like to thank Dr. Colin Combs for providing the α-tubulin antibodies and goat anti-mouse IgM used for Western blot analysis.

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  1. Department of Pharmacology, Physiology, and Therapeutics, School of Medicine and Health Sciences, University of North Dakota, 501 North Columbia Road, Room 3742, Grand Forks, ND, 58203, USA

    Mahmoud L. Soliman & Thad A. Rosenberger

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  1. Mahmoud L. Soliman
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  2. Thad A. Rosenberger
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Correspondence to Thad A. Rosenberger.

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Soliman, M.L., Rosenberger, T.A. Acetate supplementation increases brain histone acetylation and inhibits histone deacetylase activity and expression. Mol Cell Biochem 352, 173–180 (2011). https://doi.org/10.1007/s11010-011-0751-3

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