ArticleCell death & disease2022
Rg3 regulates myocardial pyruvate metabolism via P300-mediated dihydrolipoamide dehydrogenase 2-hydroxyisobutyrylation in TAC-induced cardiac hypertrophy.
Article in Cell death & disease, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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23 citing papers in PubMed, 31 citations in OpenAlex.
- Cuproptosis: New Perspectives for Prevention and Treatment of Osteoarthritis with Chinese Medicine Extracts.Chinese journal of integrative medicine · 2026Review
- Regulation of pyruvate dehydrogenase complex: Dancing to different drums in cancer.International journal of cancer · 2026Review
- De-2-hydroxyisobutyrylation of clusterin modulates neuropathology and memory deficits in an Alzheimer's disease mouse model.Cell communication and signaling : CCS · 2026Article
- The mechanism and treatment of protein acylation modification in cardiovascular disease: a narrative review.Frontiers in pharmacology · 2026Review
- Integrating Traditional Wisdom With Modern Science: Ginsenosides as Antiheart Failure Agents.Cardiovascular therapeutics · 2026Review
- The effect of cuproptosis-related gene Atox1 on cardiac hypertrophy in heart failure was investigated based on bioinformatics analysis.Scientific reports · 2025Article
- Post-translational acylation of proteins in cardiac hypertrophy.Nature reviews. Cardiology · 2025Review
- HuoXue QianYang QuTan recipe attenuates myocardial hypertrophy in obese hypertensive rats by regulating MPC1/MCT4 mediated pyruvate-lactate metabolic axis.Chinese medicine · 2025Article
- High-fat intake during lactation ameliorates cardiac fatty acid metabolic disorders and dysfunction in mouse offspring undergoing prenatal poly (I:C) stimulation.Acta pharmacologica Sinica · 2025Article
- Potentiation of paclitaxel-induced apoptosis in a non-small cell lung cancer model using the traditional Chinese drug huaier: Network pharmacology analysis, experimental verification, and clinical impact.International journal of clinical pharmacology and therapeutics · 2025Article
- Advances in pharmacological research on myocardial remodeling agents: A decade in review.Medicine · 2025Review
- Atlas of lysine propionylation of human right atrium and ALDH6A1-NADH pathway in new-onset atrial fibrillation after coronary surgery.Communications biology · 2025Article
- Comparative Analysis of Volatile Organic Compounds in Different Parts of Ginseng Powder Using Gas Chromatography-Ion Mobility Spectrometry.Molecules (Basel, Switzerland) · 2025Article
- Sex-Specific Improvements in Myocardial Function and Angiogenesis with SGLT-2 Inhibitor Canagliflozin in a Swine Model of Metabolic Syndrome.International journal of molecular sciences · 2025Article
- FGF21 protects against HFpEF by improving cardiac mitochondrial bioenergetics in mice.Nature communications · 2025Article
- Modulation of Abnormal Vasoconstriction Through 2-Hydroxyisobutyrylation of Tropomyosin 3 Lys141: Targeting Histone Deacetylase 3 as a Key Approach.Journal of the American Heart Association · 2025Article
- Establishing a robust triangulation framework to explore the relationship between hearing loss and Parkinson's disease.NPJ Parkinson's disease · 2025Article
- FBLN7 KO attenuates age-related cardiac fibrosis by promoting TGFBR3/ALK1/Smad1 signaling and inhibiting the profibrotic phenotypes of cardiac fibroblasts.Theranostics · 2025Article
- Dual activation of GCGR/GLP1R signaling ameliorates intestinal fibrosisActa pharmaceutica Sinica. B · 2025Article
- Deciphering the Role of Copper Homeostasis in Atherosclerosis: From Molecular Mechanisms to Therapeutic Targets.International journal of molecular sciences · 2024Review
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13 authors at 3 institutions in 1 country.
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Abstract
The failing heart is characterized by an increase in glucose uptake and glycolytic rates that is not accompanied by a concomitant increase in glucose oxidation. Lower coupling of glucose oxidation to glycolysis possibly owes to unchanged or reduced pyruvate oxidation in mitochondria. Therefore, increasing pyruvate oxidation may lead to new therapies for heart disease. Dihydrolipoamide dehydrogenase (DLD) is a component of the pyruvate dehydrogenase complex (PDH). DLD mutations or defects are closely associated with metabolic diseases. However, few studies explore the effects of DLD mutants or acylation status on PDH activity and pyruvate metabolism. P300 is protein 2-hydroxyisobutyryltransferases in cells, and P300-dependent lysine 2-hydroxyisobutyrylation of glycolytic enzymes affects glucose metabolism. However, there are no relevant reports on the effect of 2-hydroxyisobutyrylation on the energy metabolism of heart failure, and it is worth further in-depth study. In this study, we showed that 2-hydroxyisobutyrylation is an essential protein translational modification (PTM) that regulates the activity of pyruvate dehydrogenase complex (PDHc). In a mouse model of transverse aortic constriction (TAC)-induced cardiac hypertrophy, the 2-hydroxyisobutylation of DLD was significantly increased, related to the decrease in PDH activity. In addition, our data provide clear evidence that DLD is a direct substrate of P300. As one of the main active ingredients of ginseng, ginsenoside Rg3 (Rg3) can reduce the 2-hydroxyisobutylation levels of DLD and restore the PDH activity by inhibiting the acyltransferase activity of P300, thereby producing beneficial effects whenever the heart is injured. Therefore, this study suggests a novel strategy for reversing myocardial hypertrophy.
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