ArticleMolecular pharmacology2012
Redox regulation by nuclear factor erythroid 2-related factor 2: gatekeeping for the basal and diabetes-induced expression of thioredoxin-interacting protein.
Article in Molecular pharmacology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 106 citations in OpenAlex.
- Trial
- Critical role of Sirtuin 6 (SIRT6) in osteoarthritis chondrocytes: the interaction among various biological processes.Annals of medicine · 2026Review
- Crosstalk Between Nrf2 and Metabolic Pathways: Redox Regulation, Glutaminolysis, and Cellular Proliferation.Cell biochemistry and biophysics · 2026Review
- Mechanisms of fetal growth restriction in gestational cholestasis: role of gut microbiota and placental redox.Frontiers in veterinary science · 2026Article
- The Role of TXNIP in Skeletal Muscle Physiology and Related Diseases: Current Perspectives.Journal of inflammation research · 2026Review
- Mechanistic Link Between Glyoxalase 1 Expression and Methylglyoxal-Induced Oncogenic Stress in Prostate Cancer.bioRxiv : the preprint server for biology · 2025Article
- Celastrol ameliorates hypoxic-ischemic brain injury in neonatal rats by reducing oxidative stress and inflammation.Pediatric research · 2024Article
- Article
- Sulforaphane acutely activates multiple starvation response pathways.Frontiers in nutrition · 2024Article
- Empagliflozin reduces endoplasmic reticulum stress associated TXNIP/NLRP3 activation in tunicamycin-stimulated aortic endothelial cells.Naunyn-Schmiedeberg's archives of pharmacology · 2024Article
- Transcriptional landscape of mitochondrial electron transport chain inhibition in renal cells.Cell biology and toxicology · 2023Article
- The role of TXNIP in cancer: a fine balance between redox, metabolic, and immunological tumor control.British journal of cancer · 2023Review
- Melatonin Protects Mouse Type A Spermatogonial Stem Cells against Oxidative Stress via The Mitochondrial Thioredoxin System.Cell journal · 2023Article
- Insights into the Molecular Mechanisms of NRF2 in Kidney Injury and Diseases.International journal of molecular sciences · 2023Review
- Targeting NEDDylation is a Novel Strategy to Attenuate Cisplatin-induced Nephrotoxicity.Cancer research communications · 2023Article
- ChemR23 signaling ameliorates cognitive impairments in diabetic mice via dampening oxidative stress and NLRP3 inflammasome activation.Redox biology · 2022Article
- Antioxidant and anti-inflammatory activities of Centratherum anthelminticum (L.) Kuntze seed oil in diabetic nephropathy via modulation of Nrf-2/HO-1 and NF-κB pathway.BMC complementary medicine and therapies · 2022Article
- The complexity of p53-mediated metabolic regulation in tumor suppression.Seminars in cancer biology · 2022Review
- Antioxidant Effects of DPP-4 Inhibitors in Early Stages of Experimental Diabetic Retinopathy.Antioxidants (Basel, Switzerland) · 2022Article
- Thioredoxin-interacting protein in diabetic retinal neurodegeneration: A novel potential therapeutic target for diabetic retinopathy.Frontiers in neuroscience · 2022Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor activated by a range of oxidants and electrophiles. The transcriptional response to endogenous oxidative cues by Nrf2 plays an important role in mammalian redox physiology and oxidative pathology. Hyperglycemia induces oxidative stress in the heart where it leads to apoptosis and ultimately cardiomyopathy. Here we investigated the mechanism by which Nrf2 suppresses oxidative stress in diabetic mouse heart. Knockout (KO) of Nrf2 induced oxidative stress and apoptosis in KO heart; diabetes further increased oxidative damage. A pathway-focused gene array revealed that Nrf2 controls the expression of 24 genes in the heart, including the gene encoding thioredoxin-interacting protein (TXNIP). Nrf2 suppressed the basal expression of Txnip in the heart and blocked induction of Txnip by high glucose by binding to an antioxidant response element (ARE) (-1286 to -1276) of the Txnip promoter. Binding of Nrf2 to ARE also suppressed the binding of MondoA to the carbohydrate response element with or without high glucose. TXNIP promoted reactive oxygen species production and apoptosis by inhibiting thioredoxin. On the other hand, Nrf2 boosted thioredoxin activity by inhibiting Txnip. The findings revealed, for the first time, that Nrf2 is a key gatekeeper of Txnip transcription, suppressing both its basal expression and MondoA-driven induction to control the thioredoxin redox signaling in diabetes.
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