ArticleMolecular and cellular biology2008
Reactive oxygen species regulate hypoxia-inducible factor 1alpha differentially in cancer and ischemia.
Article in Molecular and cellular biology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 105 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
105 citing papers in PubMed, 189 citations in OpenAlex.
- Effects of remote ischemic postconditioning on HIF-1α and other markers in on-pump cardiac surgery.General thoracic and cardiovascular surgery · 2022Trial
- Expression of the oxygen-sensitive transcription factor subunit HIF-1α in patients suffering from secondary Raynaud syndrome.Acta pharmacologica Sinica · 2019Trial
- Group 3 Pulmonary Hypertension: Mechanistic Insights, Clinical Challenges, and Evolving Therapies.Journal of clinical medicine · 2026Review
- Beyond Food Preservation: Translational Perspectives of Synthetic Antioxidants.Antioxidants (Basel, Switzerland) · 2026Review
- β-catenin-driven innate and metabolic reprograming in macrophages fuel T-cell-dependent inflammation in Toxoplasma gondii infection: implications for therapeutic intervention.Cell death & disease · 2026Article
- miRNA675-5p inhibitor's dual role as novel therapeutic alternative or sensitizing treatment in resistant glioma models.Molecular therapy. Nucleic acids · 2026Article
- Natural Phytochemicals as Inhibitors of HIF-1α in Breast Cancer: Review of Preclinical Evidence and Future Prospects.Current issues in molecular biology · 2026Review
- ROS-scavenging nanomaterials as emerging tools for bone tissue regeneration: A comprehensive review of recent progress.Acta pharmaceutica Sinica. B · 2025Review
- The research progress of α-ketoglutarate in osteoarthritis.Biochemistry and biophysics reports · 2025Review
- Vascular endothelial generating factor pathway in ovarian cancer.Journal of ovarian research · 2025Review
- Sensing within: Mitochondrial inside-out signal transduction.Cell chemical biology · 2025Review
- Discovery of platelet glycoprotein VI receptor antagonists and their neuroprotective activity: an in silico, in vitro, and in vivo study.3 Biotech · 2025Article
- Synergistic Effect of Prolonged Oxygenation and Reactive Oxygen Species Scavenging on Diabetic Wound Healing Using an Injectable Thermoresponsive Hydrogel.Small (Weinheim an der Bergstrasse, Germany) · 2025Article
- Mitochondrial ROS and HIF-1α signaling mediate synaptic plasticity in the critical period.PLoS biology · 2025Article
- Tibetan PHD2D4E;C127S variant protects from viral diseases in hypoxia, but predispose to infections in normoxia via HIFα:IFN axis.PLoS pathogens · 2025Article
- GSTP1 knockdown induces metabolic changes affecting energy production and lipid balance in pancreatic cancer cells.Molecular & cellular oncology · 2025Article
- Impaired endothelial function contributes to cardiac dysfunction: role of mitochondrial dynamics.American journal of physiology. Heart and circulatory physiology · 2025Review
- Metal Peroxide Nanoparticles for Modulating the Tumor Microenvironment: Current Status and Recent Prospects.Cancers · 2024Review
- p53 Orchestrates Cancer Metabolism: Unveiling Strategies to Reverse the Warburg Effect.Bulletin of mathematical biology · 2024Article
- HIV coinfection exacerbates HBV-induced liver fibrogenesis through a HIF-1α- and TGF-β1-dependent pathway.Journal of hepatology · 2024Article
45 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
In exercise, as well as cancer and ischemia, hypoxia-inducible factor 1 (HIF1) transcriptionally activates hundreds of genes vital for cell homeostasis and angiogenesis. While potentially beneficial in ischemia, upregulation of the HIF1 transcription factor has been linked to inflammation, poor prognosis in many cancers, and decreased susceptibility of tumors to radiotherapy and chemotherapy. Considering HIF1's function, HIF1alpha protein and its hydroxylation cofactors look increasingly attractive as therapeutic targets. Independently, antioxidants have shown promise in lowering the risk of some cancers and improving neurological and cardiac function following ischemia. The mechanism of how different antioxidants and reactive oxygen species influence HIF1alpha expression has drawn interest and intense debate. Here we present an experimentally based computational model of HIF1alpha protein degradation that represents how reactive oxygen species and antioxidants likely affect the HIF1 pathway differentially in cancer and ischemia. We use the model to demonstrate effects on HIF1alpha expression from combined doses of five potential therapeutically targeted compounds (iron, ascorbate, hydrogen peroxide, 2-oxoglutarate, and succinate) influenced by cellular oxidation-reduction and involved in HIF1alpha hydroxylation. Results justify the hypothesis that reactive oxygen species work by two opposite ways on the HIF1 system. We also show how tumor cells and cells under ischemic conditions would differentially respond to reactive oxygen species via changes to HIF1alpha expression over the course of hours to days, dependent on extracellular hydrogen peroxide levels and largely independent of initial intracellular levels, during hypoxia.
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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.