ArticleThe Biochemical journal2007
NOX4 activity is determined by mRNA levels and reveals a unique pattern of ROS generation.
Article in The Biochemical journal, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 334 papers, 1 of them a synthesis that pooled it.
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Who cites it
334 citing papers in PubMed, 1 synthesis or guideline pooled it, 619 citations in OpenAlex.
- NADPH oxidases in Parkinson's disease: a systematic review.Molecular neurodegeneration · 2017Pooled it
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- Role of NADPH Oxidases as Novel Therapeutic Targets for the Impaired Neurovascular Unit in the Early Stage of Diabetic Retinopathy.International journal of molecular sciences · 2026Review
- Mitochondrial remodeling in heart failure with reduced ejection fraction.Frontiers in physiology · 2026Review
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- Reactive oxygen species (ROS) in cancer: from redox signaling and metabolic plasticity to therapeutic vulnerabilities.Exploration of targeted anti-tumor therapy · 2026Review
- Beyond Radical Scavengers: Focus on NADPH Oxidases (NOX) Inhibitors as New Agents for Antioxidant Therapy in Alzheimer's Disease.Antioxidants (Basel, Switzerland) · 2025Review
- The Dual Role of NOX4 in Cardiovascular Diseases: Driver of Oxidative Stress and Mediator of Adaptive Remodeling.Antioxidants (Basel, Switzerland) · 2025Review
- QMRInternational journal of molecular sciences · 2025Article
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- Comprehensive Analysis of Metabolites and Biological Endpoints Providing New Insights into the Tolerance of Wheat Under Sulfamethoxazole Stress.International journal of molecular sciences · 2025Article
- Redox Mechanisms Driving Skin Fibroblast-to-Myofibroblast Differentiation.Antioxidants (Basel, Switzerland) · 2025Article
- Integrated Analysis of Metabolites and Biological Endpoints Bring New Insights into Sulfamethoxazole Stress Tolerance in Ryegrass.Plants (Basel, Switzerland) · 2025Article
- Ferroptosis in schizophrenia: Mechanisms and therapeutic potentials (Review).Molecular medicine reports · 2025Review
- Bone Adaptations to a Whole Body Vibration Protocol in Murine Models of Different Ages: A Preliminary Study on Structural Changes and Biomarker Evaluation.Journal of functional morphology and kinesiology · 2025Article
- TNIK: A redox sensor in endothelial cell permeability.Science advances · 2024Article
- Oxidative Stress in Kidney Injury and Hypertension.Antioxidants (Basel, Switzerland) · 2024Review
- Molecular Roles of NADPH Oxidase-Mediated Oxidative Stress in Alzheimer's Disease: Isoform-Specific Contributions.International journal of molecular sciences · 2024Review
- Specific NOX4 Inhibition Preserves Mitochondrial Function and Dampens Kidney Dysfunction Following Ischemia-Reperfusion-Induced Kidney Injury.Antioxidants (Basel, Switzerland) · 2024Article
274 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
NOX4 is an enigmatic member of the NOX (NADPH oxidase) family of ROS (reactive oxygen species)-generating NADPH oxidases. NOX4 has a wide tissue distribution, but the physiological function and activation mechanisms are largely unknown, and its pharmacology is poorly understood. We have generated cell lines expressing NOX4 upon tetracycline induction. Tetracycline induced a rapid increase in NOX4 mRNA (1 h) followed closely (2 h) by a release of ROS. Upon tetracycline withdrawal, NOX4 mRNA levels and ROS release decreased rapidly (<24 h). In membrane preparations, NOX4 activity was selective for NADPH over NADH and did not require the addition of cytosol. The pharmacological profile of NOX4 was distinct from other NOX isoforms: DPI (diphenyleneiodonium chloride) and thioridazine inhibited the enzyme efficiently, whereas apocynin and gliotoxin did not (IC(50)>100 muM). The pattern of NOX4-dependent ROS generation was unique: (i) ROS release upon NOX4 induction was spontaneous without need for a stimulus, and (ii) the type of ROS released from NOX4-expressing cells was H(2)O(2), whereas superoxide (O(2)(-)) was almost undetectable. Probes that allow detection of intracellular O(2)(-) generation yielded differential results: DHE (dihydroethidium) fluorescence and ACP (1-acetoxy-3-carboxy-2,2,5,5-tetramethylpyrrolidine) ESR measurements did not detect any NOX4 signal, whereas a robust signal was observed with NBT. Thus NOX4 probably generates O(2)(-) within an intracellular compartment that is accessible to NBT (Nitro Blue Tetrazolium), but not to DHE or ACP. In conclusion, NOX4 has a distinct pharmacology and pattern of ROS generation. The close correlation between NOX4 mRNA and ROS generation might hint towards a function as an inducible NOX isoform.
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