ArticleToxicological sciences : an official journal of the Society of Toxicology2016
Cardiac-Specific Deletion of the Pdha1 Gene Sensitizes Heart to Toxicological Actions of Ischemic Stress.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 27 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
27 citing papers in PubMed, 45 citations in OpenAlex.
- PDHA1 Hyperactivation-Mediated Glucose Metabolism Reprogramming Fuels Neutrophil NETosis and Promotes Acute Lung Injury.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- RND3 Enhances Cardiac Glucose Metabolism Through Inhibiting ACAT1-Dependent PDHA1 Acetylation and Protects Against Ischemia-Reperfusion Injury.Circulation · 2026Article
- Mitochondrial PDHA1 acetylation orchestrates lactate-dependent epigenetic reprogramming to promote fibrosis via NUAK2.Cellular and molecular life sciences : CMLS · 2026Article
- Animal models of pyruvate dehydrogenase complex deficiency: insight into mechanisms of cerebral abnormalities and tissue-specific role in metabolism.Frontiers in medicine · 2026Review
- Astragaloside IV increases PDHA1 in mesenchymal stem cell exosomes to treat myocardial infarction.Scientific reports · 2025Article
- Cardiac substrate metabolism in type 2 diabetes.The Biochemical journal · 2025Review
- Leptin drives glucose metabolism to promote cardiac protection via OPA1-mediated HDAC5 translocation and Glut4 transcription.Functional & integrative genomics · 2025Article
- Mitochondrial heterogeneity in diseases.Signal transduction and targeted therapy · 2023Review
- RNA-Seq analysis of obese Pdha1Experimental animals · 2023Article
- Sestrin2 as a gatekeeper of cellular homeostasis: Physiological effects for the regulation of hypoxia-related diseases.Journal of cellular and molecular medicine · 2021Review
- Cardiac Energy Metabolism in Heart Failure.Circulation research · 2021Review
- Integrative transcriptomic analysis of tissue-specific metabolic crosstalk after myocardial infarction.eLife · 2021Article
- Octanoate is differentially metabolized in liver and muscle and fails to rescue cardiomyopathy in CPT2 deficiency.Journal of lipid research · 2021Article
- Nutritional modulation of heart failure in mitochondrial pyruvate carrier-deficient mice.Nature metabolism · 2020Article
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- Changes in Myocardial Metabolism Preceding Sudden Cardiac Death.Frontiers in physiology · 2020Review
- Article
- Alleviation of sepsis‑induced cardiac dysfunction by overexpression of Sestrin2 is associated with inhibition of p‑S6K and activation of the p‑AMPK pathway.Molecular medicine reports · 2019Article
- Dichloroacetate Ameliorates Cardiac Dysfunction Caused by Ischemic Insults Through AMPK Signal Pathway-Not Only Shifts Metabolism.Toxicological sciences : an official journal of the Society of Toxicology · 2019Article
- Cardiac Specific Knockout of p53 Decreases ER Stress-Induced Mitochondrial Damage.Frontiers in cardiovascular medicine · 2019Article
Corrections and comments
- Erratum issued
Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
Pyruvate dehydrogenase (PDH) plays a key role in aerobic energy metabolism and occupies a central crossroad between glycolysis and the tricarboxylic acid cycle. We generated inducible cardiac-specific PDH E1α knockout (CreER(T2)-PDH(flox/flox)) mice that demonstrated a high mortality rate. It was hypothesized that PDH modulating cardiac glucose metabolism is crucial for heart functions under normal physiological and/or stress conditions. The myocardial infarction was conducted by a ligation of the left anterior descending coronary arteries. Cardiac PDH E1α deficiency caused large myocardial infarcts size and macrophage infiltration in the hearts (P < .01 vs wild-type [WT]). Wheat germ agglutinin and Masson trichrome staining revealed significantly increased hypertrophy and fibrosis in PDH E1α-deficient hearts (P < .05 vs WT). Measurements of heart substrate metabolism in an ex vivo working heart perfusion system demonstrated a significant impairment of glucose oxidation in PDH E1α-deficient hearts during ischemia/reperfusion (P < .05 vs WT). Dichloroacetate, a PDH activator, increased glucose oxidation in WT hearts during ischemia/reperfusion and reduced myocardial infarct size in WT, but not in PDH E1α-deficient hearts. Immunoblotting results demonstrated that cardiac PDH E1α deficiency leads to an impaired ischemic AMP-activated protein kinase activation through Sestrin2-liver kinase B1 interaction which is responsible for an increased susceptibility of PDH E1α-deficient heart to ischemic insults. Thus, cardiac PDH E1α deficiency impairs ischemic AMP-activated protein kinase signaling and sensitizes hearts to the toxicological actions of ischemic stress.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.