ArticleMolecular & cellular proteomics : MCP2013
Regulation of acetylation restores proteolytic function of diseased myocardium in mouse and human.
Article in Molecular & cellular proteomics : MCP, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 50 citations in OpenAlex.
- Cleaving Expectations: A Review of Proteasome Functional and Catalytic Diversity.Biomolecules · 2025Review
- HDACs and Their Inhibitors on Post-Translational Modifications: The Regulation of Cardiovascular Disease.Cells · 2025Review
- Activators of the 26S proteasome when protein degradation increases.Experimental & molecular medicine · 2025Review
- Oxidative Post-translational Protein Modifications upon Ischemia/Reperfusion Injury.Antioxidants (Basel, Switzerland) · 2024Article
- Targeting histone deacetylase in cardiac diseases.Frontiers in physiology · 2024Review
- Potential Role of Lysine Acetylation and Autophagy in Brown Film Formation and Postripening of Lentinula edodes Mycelium.Microbiology spectrum · 2023Article
- Erythroid mitochondrial retention triggers myeloid-dependent type I interferon in human SLE.Cell · 2021Article
- Proteasome Biology: Chemistry and Bioengineering Insights.Polymers · 2020Review
- Post-Translational Modifications of Extracellular Proteasome.Molecules (Basel, Switzerland) · 2020Article
- Regulation of metabolism by mitochondrial enzyme acetylation in cardiac ischemia-reperfusion injury.Biochimica et biophysica acta. Molecular basis of disease · 2020Review
- Functional Analysis of Differentially Expressed Acetylated Spermatozoal Proteins in Infertile Men with Unilateral and Bilateral Varicocele.International journal of molecular sciences · 2020Article
- The Role and Regulation of Autophagy and the Proteasome During Aging and Senescence in Plants.Genes · 2019Review
- Regulation of Proteasome Activity by (Post-)transcriptional Mechanisms.Frontiers in molecular biosciences · 2019Review
- Review
- Protein Modifications with Ubiquitin as Response to Cerebral Ischemia-Reperfusion Injury.Translational stroke research · 2018Review
- Emerging Evidence of Epigenetic Modifications in Vascular Complication of Diabetes.Frontiers in endocrinology · 2017Review
- Precise assembly and regulation of 26S proteasome and correlation between proteasome dysfunction and neurodegenerative diseases.BMB reports · 2016Review
- The life cycle of the 26S proteasome: from birth, through regulation and function, and onto its death.Cell research · 2016Review
- Myofibril growth during cardiac hypertrophy is regulated through dual phosphorylation and acetylation of the actin capping protein CapZ.Cellular signalling · 2016Article
- Histone Deacetylase (HDAC) Inhibitors - emerging roles in neuronal memory, learning, synaptic plasticity and neural regeneration.Current neuropharmacology · 2016Review
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
Abstract
Proteasome complexes play essential roles in maintaining cellular protein homeostasis and serve fundamental roles in cardiac function under normal and pathological conditions. A functional detriment in proteasomal activities has been recognized as a major contributor to the progression of cardiovascular diseases. Therefore, approaches to restore proteolytic function within the setting of the diseased myocardium would be of great clinical significance. In this study, we discovered that the cardiac proteasomal activity could be regulated by acetylation. Histone deacetylase (HDAC) inhibitors (suberoylanilide hydroxamic acid and sodium valproate) enhanced the acetylation of 20S proteasome subunits in the myocardium and led to an elevation of proteolytic capacity. This regulatory paradigm was present in both healthy and acutely ischemia/reperfusion (I/R) injured murine hearts, and HDAC inhibition in vitro restored proteolytic capacities to baseline sham levels in injured hearts. This mechanism of regulation was also viable in failing human myocardium. With 20S proteasomal complexes purified from murine myocardium treated with HDAC inhibitors in vivo, we confirmed that acetylation of 20S subunits directly, at least in part, presents a molecular explanation for the improvement in function. Furthermore, using high-resolution LC-MS/MS, we unraveled the first cardiac 20S acetylome, which identified the acetylation of nine N-termini and seven internal lysine residues. Acetylation on four lysine residues and four N-termini on cardiac proteasomes were novel discoveries of this study. In addition, the acetylation of five lysine residues was inducible via HDAC inhibition, which correlated with the enhancement of 20S proteasomal activity. Taken as a whole, our investigation unveiled a novel mechanism of proteasomal function regulation in vivo and established a new strategy for the potential rescue of compromised proteolytic function in the failing heart using HDAC inhibitors.
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