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- W4386465400 abstract "Identifying branched-chain amino acid (BCAA) oxidation enzymes in the nucleus led us to predict that they are a source of propionyl-CoA that are utilized for histone propionylation and, thereby, regulate gene expression. To investigate the effects of BCAA on the development of cardiac hypertrophy and failure, we applied pressure overload on the heart in mice maintained on a diet with standard levels of BCAA (BCAA-control) versus a BCAA-free diet. The former was associated with an increase in histone H3K23-propionyl (H3K23Pr) at the promoters of upregulated genes [e.g., cell signaling and extracellular matrix genes] and a decrease at the promoters of downregulated genes [e.g., electron transfer complex (ETC I-V) and metabolic genes]. Intriguingly, the BCAA-free diet tempered the increases in promoter-H3K23Pr, thus, reducing collagen gene expression and fibrosis during cardiac hypertrophy. Conversely, the BCAA-free diet inhibited the reductions in promoter-H3K23Pr and abolished the downregulation of ETC I-V subunits, enhanced mitochondrial respiration, and curbed progression of cardiac hypertrophy. Thus, lowering the intake of BCAA reduces pressure overload-induced changes in histone propionylation-dependent gene expression in the heart, which retards the development of cardiomyopathy." @default.
- W4386465400 created "2023-09-06" @default.
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- W4386465400 date "2023-09-05" @default.
- W4386465400 modified "2023-09-27" @default.
- W4386465400 title "Reducing branched-chain amino acids improves cardiac stress response in mice by decreasing histone H3K23 propionylation" @default.
- W4386465400 doi "https://doi.org/10.1172/jci169399" @default.
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