ArticleBiochemistry2013
Redox modulation of endothelial nitric oxide synthase by glutaredoxin-1 through reversible oxidative post-translational modification.
Article in Biochemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
38 citing papers in PubMed, 69 citations in OpenAlex.
- Glutathione Biology in Neurodegenerative and Metabolic Diseases: Molecular Mechanisms, Pathophysiological Roles, and Therapeutic Perspectives.International journal of molecular sciences · 2026Review
- NO-cGMP Signaling in Endothelial Function of the Healthy and Inflamed Dental Pulp.International journal of molecular sciences · 2025Review
- Tobacco cigarette smoking induces cerebrovascular dysfunction followed by oxidative neuronal injury with the onset of cognitive impairment.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2025Article
- Promotion of nitric oxide production: mechanisms, strategies, and possibilities.Frontiers in physiology · 2025Review
- Oxidative stress and the role of redox signalling in chronic kidney disease.Nature reviews. Nephrology · 2024Review
- Vascular Redox Signaling, Endothelial Nitric Oxide Synthase Uncoupling, and Endothelial Dysfunction in the Setting of Transportation Noise Exposure or Chronic Treatment with Organic Nitrates.Antioxidants & redox signaling · 2023Review
- Endothelial dysfunction due to eNOS uncoupling: molecular mechanisms as potential therapeutic targets.Cellular & molecular biology letters · 2023Article
- Chaperone-Mediated Autophagy of eNOS in Myocardial Ischemia-Reperfusion Injury.Circulation research · 2021Article
- The Calcium Signaling Mechanisms in Arterial Smooth Muscle and Endothelial Cells.Comprehensive Physiology · 2021Article
- Glutathione in Protein Redox Modulation through S-Glutathionylation and S-Nitrosylation.Molecules (Basel, Switzerland) · 2021Review
- S-glutathionylation, friend or foe in cardiovascular health and disease.Redox biology · 2020Review
- Role of Glutaredoxin-1 and Glutathionylation in Cardiovascular Diseases.International journal of molecular sciences · 2020Review
- Oxidative stress and inflammation contribute to traffic noise-induced vascular and cerebral dysfunction via uncoupling of nitric oxide synthases.Redox biology · 2020Review
- Endothelial Dysfunction: Is There a Hyperglycemia-Induced Imbalance of NOX and NOS?International journal of molecular sciences · 2019Review
- High-Dose Astaxanthin Supplementation Suppresses Antioxidant Enzyme Activity during Moderate-Intensity Swimming Training in Mice.Nutrients · 2019Article
- Role of Nitric Oxide and Hydrogen Sulfide in Ischemic Stroke and the Emergent Epigenetic Underpinnings.Molecular neurobiology · 2019Review
- Thioredoxin and glutaredoxin regulate metabolism through different multiplex thiol switches.Redox biology · 2019Article
- New Therapeutic Implications of Endothelial Nitric Oxide Synthase (eNOS) Function/Dysfunction in Cardiovascular Disease.International journal of molecular sciences · 2019Review
- Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their RegulationPhysiological reviews · 2019Review
- Use of Computational Biochemistry for Elucidating Molecular Mechanisms of Nitric Oxide Synthase.Computational and structural biotechnology journal · 2019Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
S-Glutathionylation is a redox-regulated modification that uncouples endothelial nitric oxide synthase (eNOS), switching its function from nitric oxide (NO) synthesis to (•)O2(-) generation, and serves to regulate vascular function. While in vitro or in vivo eNOS S-glutathionylation with modification of Cys689 and Cys908 of its reductase domain is triggered by high levels of glutathione disulfide (GSSG) or oxidative thiyl radical formation, it remains unclear how this process may be reversed. Glutaredoxin-1 (Grx1), a cytosolic and glutathione-dependent enzyme, can reverse protein S-glutathionylation; however, its role in regulating eNOS S-glutathionylation remains unknown. We demonstrate that Grx1 in the presence of glutathione (GSH) (1 mM) reverses GSSG-mediated eNOS S-glutathionylation with restoration of NO synthase activity. Because Grx1 also catalyzes protein S-glutathionylation with an increased [GSSG]/[GSH] ratio, we measured its effect on eNOS S-glutathionylation when the [GSSG]/[GSH] ratio was >0.2, which can occur in cells and tissues under oxidative stress, and observed an increased level of eNOS S-glutathionylation with a marked decrease in eNOS activity without uncoupling. This eNOS S-glutathionylation was reversed with a decrease in the [GSSG]/[GSH] ratio to <0.1. Liquid chromatography and tandem mass spectrometry identified a new site of eNOS S-glutathionylation by Grx1 at Cys382, on the surface of the oxygenase domain, without modification of Cys689 or Cys908, each of which is buried within the reductase. Furthermore, Grx1 was demonstrated to be a protein partner of eNOS in vitro and in normal endothelial cells, supporting its role in eNOS redox regulation. In endothelial cells, Grx1 inhibition or gene silencing increased the level of eNOS S-glutathionylation and decreased the level of cellular NO generation. Thus, Grx1 can exert an important role in the redox regulation of eNOS in cells.
Indexed as
Identifiers
What OpenQuestion holds
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.