ArticleThe Journal of clinical investigation2012
Deletion of thioredoxin-interacting protein in mice impairs mitochondrial function but protects the myocardium from ischemia-reperfusion injury.
Article in The Journal of clinical investigation, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers.
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Who cites it
82 citing papers in PubMed, 155 citations in OpenAlex.
- Txnip/PDK4-Mediated Hyperdependence on Fatty-Acid Oxidation Amplifies Susceptibility of Diabetic Myocardium to Ischemia-Reperfusion Damage.Journal of diabetes · 2026Article
- Mutations in the Txnip PPXY motifs protect against myocardial infarction despite enhanced protein stability.American journal of physiology. Heart and circulatory physiology · 2026Article
- ALCAT1 promotes diabetic cardiomyopathy by linking myocardial tetralinoleoyl cardiolipin deficiency to lipotoxicity.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Astrocyte Bioenergetic Remodeling as a Central Trait of Disrupted Glucocorticoid Signaling: Mechanisms and Implications for Stress Vulnerability.Journal of neurochemistry · 2026Review
- Differential expression of glycolysis-related genes and their potential immune mechanisms in acute myocardial infarction.Journal of cardiothoracic surgery · 2025Article
- TXNIP knockdown ameliorates hepatic ischemia/reperfusion injury by inhibiting apoptosis and improving mitochondrial dysfunction via HIF-1α.Molecular and cellular biochemistry · 2025Article
- Large-scale single-nuclei profiling identifies role for ATRNL1 in atrial fibrillation.Nature communications · 2024Article
- Blockade of thromboxane A2 signaling attenuates ethanol-induced myocardial inflammatory response in mice.Alcohol, clinical & experimental research · 2024Article
- Review
- High-Density Lipoproteins at the Interface between the NLRP3 Inflammasome and Myocardial Infarction.International journal of molecular sciences · 2024Review
- Geniposide alleviates post-myocardial infarction-induced pyroptosis by modulating the thioredoxin-interacting protein/NLRP3 signaling pathway.CytoJournal · 2024Article
- Integration single-cell and bulk RNA-sequencing data to reveal senescence gene expression profiles in heart failure.Heliyon · 2023Article
- The Function of MondoA and ChREBP Nutrient-Sensing Factors in Metabolic Disease.International journal of molecular sciences · 2023Review
- Mechanism of Cone Degeneration in Retinitis Pigmentosa.Cellular and molecular neurobiology · 2023Review
- Exploration of the Antioxidant Effect of Spermidine on the Ovary and Screening and Identification of Differentially Expressed Proteins.International journal of molecular sciences · 2023Article
- Targeting NEDDylation is a Novel Strategy to Attenuate Cisplatin-induced Nephrotoxicity.Cancer research communications · 2023Article
- Physiological and Pathophysiological Roles of Thioredoxin Interacting Protein: A Perspective on Redox Inflammation and Metabolism.Antioxidants & redox signaling · 2023Review
- Interaction of ARRDC4 With GLUT1 Mediates Metabolic Stress in the Ischemic Heart.Circulation research · 2022Article
- Cyclophilin a represses reactive oxygen species generation and death of hypoxic non-small-cell lung cancer cells by degrading thioredoxin-interacting protein.Cell cycle (Georgetown, Tex.) · 2022Article
- ITCH facilitates proteasomal degradation of TXNIP in hypoxia- induced lung cancer cells.Thoracic cancer · 2022Article
22 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
Abstract
Classic therapeutics for ischemic heart disease are less effective in individuals with the metabolic syndrome. As the prevalence of the metabolic syndrome is increasing, better understanding of cardiac metabolism is needed to identify potential new targets for therapeutic intervention. Thioredoxin-interacting protein (Txnip) is a regulator of metabolism and an inhibitor of the antioxidant thioredoxins, but little is known about its roles in the myocardium. We examined hearts from Txnip-KO mice by polony multiplex analysis of gene expression and an independent proteomic approach; both methods indicated suppression of genes and proteins participating in mitochondrial metabolism. Consistently, Txnip-KO mitochondria were functionally and structurally altered, showing reduced oxygen consumption and ultrastructural derangements. Given the central role that mitochondria play during hypoxia, we hypothesized that Txnip deletion would enhance ischemia-reperfusion damage. Surprisingly, Txnip-KO hearts had greater recovery of cardiac function after an ischemia-reperfusion insult. Similarly, cardiomyocyte-specific Txnip deletion reduced infarct size after reversible coronary ligation. Coordinated with reduced mitochondrial function, deletion of Txnip enhanced anaerobic glycolysis. Whereas mitochondrial ATP synthesis was minimally decreased by Txnip deletion, cellular ATP content and lactate formation were higher in Txnip-KO hearts after ischemia-reperfusion injury. Pharmacologic inhibition of glycolytic metabolism completely abolished the protection afforded the heart by Txnip deficiency under hypoxic conditions. Thus, although Txnip deletion suppresses mitochondrial function, protection from myocardial ischemia is enhanced as a result of a coordinated shift to enhanced anaerobic metabolism, which provides an energy source outside of mitochondria.
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