Measuring acetyl-CoA and acetylated histone turnover in vivo: Effect of a high fat diet.

Autor: Arias-Alvarado A; Department of Pharmaceutical Sciences, Northeast Ohio Medical University, Rootstown, OH, 44272, USA., Aghayev M; Department of Pharmaceutical Sciences, Northeast Ohio Medical University, Rootstown, OH, 44272, USA., Ilchenko S; Department of Pharmaceutical Sciences, Northeast Ohio Medical University, Rootstown, OH, 44272, USA., Rachdaoui N; Department of Animal Sciences, Rutgers, The State University of New Jersey, New Brunswick, NJ, 08901, USA., Lepp J; Department of Pharmaceutical Sciences, Northeast Ohio Medical University, Rootstown, OH, 44272, USA., Tsai TH; Department of Mathematical Sciences, Kent State University, Kent, OH, 44242, USA., Zhang GF; Division of Division of Endocrinology, Metabolism and Nutrition, Duke Molecular Physiology Institute, And Department of Medicine, Duke University, Durham, NC, 27701, USA., Previs S; Merck & Co., Inc, 2000 Galloping Hill Rd, Kenilworth, NJ, 07033, USA., Kasumov T; Department of Pharmaceutical Sciences, Northeast Ohio Medical University, Rootstown, OH, 44272, USA; Departments of Gastroenterology, Hepatology and Nutrition, Cleveland Clinic Foundation, Cleveland, OH, 44195, USA. Electronic address: tkasumov@neomed.edu.
Jazyk: angličtina
Zdroj: Analytical biochemistry [Anal Biochem] 2021 Feb 15; Vol. 615, pp. 114067. Date of Electronic Publication: 2020 Dec 16.
DOI: 10.1016/j.ab.2020.114067
Abstrakt: Cellular availability of acetyl-CoA, a central intermediate of metabolism, regulates histone acetylation. The impact of a high-fat diet (HFD) on the turnover rates of acetyl-CoA and acetylated histones is unknown. We developed a method for simultaneous measurement of acetyl-CoA and acetylated histones kinetics using a single 2 H 2 O tracer, and used it to examine effect of HFD-induced perturbations on hepatic histone acetylation in LDLR -/- mice, a mouse model of non-alcoholic fatty liver disease (NAFLD). Mice were given 2 H 2 O in the drinking water and the kinetics of hepatic acetyl-CoA, histones, and acetylated histones were quantified based on their 2 H-labeling. Consumption of a high fat Western-diet (WD) for twelve weeks led to decreased acetylation of hepatic histones (p< 0.05), as compared to a control diet. These changes were associated with 1.5-3-fold increased turnover rates of histones without any change in acetyl-CoA flux. Acetylation significantly reduced the stability of histones and the turnover rates of acetylated peptides were correlated with the number of acetyl groups in neighboring lysine sites. We conclude that 2 H 2 O-method can be used to study metabolically controlled histone acetylation and acetylated histone turnover in vivo.
(Copyright © 2020 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: