ArticleArthritis research & therapy2016
Reduced glutathione as a physiological co-activator in the activation of peptidylarginine deiminase.
Article in Arthritis research & therapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 57 citations in OpenAlex.
- Mapping the Substrate Specificity Landscape of PAD2 and PAD4 Enzymes.Chembiochem : a European journal of chemical biology · 2026Article
- Inhibition of <italic>Pseudomonas aeruginosa</italic> Biofilm Formation by Peptidyl-Arginine Deiminases 2 and 4.Journal of innate immunity · 2026Article
- Neutrophil-Derived Peptidyl Arginine Deiminase Activity Contributes to Pulmonary Emphysema by Enhancing Elastin Degradation.Journal of immunology (Baltimore, Md. : 1950) · 2024Article
- Exploring Immune Redox Modulation in Bacterial Infections: Insights into Thioredoxin-Mediated Interactions and Implications for Understanding Host-Pathogen Dynamics.Antioxidants (Basel, Switzerland) · 2024Review
- The monocyte cell surface is a unique site of autoantigen generation in rheumatoid arthritis.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Current insights into the role of citrullination in thrombosis.Current opinion in chemical biology · 2023Review
- Selective inhibition of peptidyl-arginine deiminase (PAD): can it control multiple inflammatory disorders as a promising therapeutic strategy?Inflammopharmacology · 2023Review
- PADs and NETs in digestive system: From physiology to pathology.Frontiers in immunology · 2023Review
- Neutrophil extracellular traps mediate deep vein thrombosis: from mechanism to therapy.Frontiers in immunology · 2023Review
- Citrullination of C1-inhibitor as a mechanism of impaired complement regulation in rheumatoid arthritis.Frontiers in immunology · 2023Article
- Endothelial Dysfunction Induced by Extracellular Neutrophil Traps Plays Important Role in the Occurrence and Treatment of Extracellular Neutrophil Traps-Related Disease.International journal of molecular sciences · 2022Review
- The Role of Oxidative Stress in Epigenetic Changes Underlying Autoimmunity.Antioxidants & redox signaling · 2022Review
- Redox-Mediated Carbamylation As a Hapten Model Applied to the Origin of Antibodies to Modified Proteins in Rheumatoid Arthritis.Antioxidants & redox signaling · 2022Review
- Glutathione in Brain Disorders and Aging.Molecules (Basel, Switzerland) · 2022Review
- Biomarkers of autoimmunity and beta cell metabolism in type 1 diabetes.Frontiers in immunology · 2022Review
- Roles, detection, and visualization of neutrophil extracellular traps in acute pancreatitis.Frontiers in immunology · 2022Review
- The Citrullination-Neutrophil Extracellular Trap Axis in Chronic Diseases.Journal of innate immunity · 2022Review
- PAD4 takes charge during neutrophil activation: Impact of PAD4 mediated NET formation on immune-mediated disease.Journal of thrombosis and haemostasis : JTH · 2021Review
- The effects of twenty-four nutrients and phytonutrients on immune system function and inflammation: A narrative review.Journal of clinical and translational research · 2021Review
- Applicability of Small-Molecule Inhibitors in the Study of Peptidyl Arginine Deiminase 2 (PAD2) and PAD4.Frontiers in immunology · 2021Article
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundCitrullination catalysed by peptidylarginine deiminases (PADs) plays an important pathogenic role in anti-citrullinated protein antibody (ACPA)-positive rheumatoid arthritis (RA) and, possibly, several other inflammatory diseases. Non-physiological reducing agents such as dithiothreitol (DTT) are normally added to the reaction buffer when determining PAD activity in vitro. We investigated the ability of reduced glutathione (GSH), the most abundant intracellular small-molecule thiol in vivo, to activate PADs.
methodsActivity of recombinant human (rh) PAD2 and PAD4, PADs contained in synovial fluid (SF) samples from RA patients and PADs released from phorbol 12-myristate 13-acetate (PMA)-stimulated cells was measured using an in-house PAD activity assay detecting citrullination of fibrinogen.
resultsNo activity of rhPAD2, rhPAD4 or PADs within SF was observed without addition of an exogenous reducing agent. Activity of both recombinant and SF PAD was observed in the presence of 1 mM DTT or 10-15 mM GSH. Following stimulation with PMA, human isolated leucocytes, but not mononuclear cells, released enzymatically active PAD, the activity of which was abolished upon pre-incubation of the cells with the glutathione reductase inhibitor 2-AAPA. No PAD activity was observed in the corresponding supernatants, but addition of exogenous GSH restored activity.
conclusionsCatalytic activity of PAD requires reducing conditions. GSH meets this requirement at concentrations comparable with those found within cells. Active PAD, reduced by GSH, is released from PMA-stimulated granulocytes, but becomes inactivated in the extracellular space.
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