ArticleFrontiers in immunology2018
Perspective on Protein Arginine Deiminase Activity-Bicarbonate Is a pH-Independent Regulator of Citrullination.
Article in Frontiers in immunology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 15 citations in OpenAlex.
- Article
- Mapping the Substrate Specificity Landscape of PAD2 and PAD4 Enzymes.Chembiochem : a European journal of chemical biology · 2026Article
- Peptidylarginine deiminase 4-mediated citrullination in human disease: molecular mechanisms and therapeutic targeting.Frontiers in pharmacology · 2026Review
- Molecular and subcellular mechanisms of vital macrophage extracellular trap formation.Frontiers in immunology · 2025Article
- Between good and evil: Complexation of the human cathelicidin LL-37 with nucleic acids.Biophysical journal · 2024Review
- Role and intervention of PAD4 in NETs in acute respiratory distress syndrome.Respiratory research · 2024Review
- The Citrullination-Neutrophil Extracellular Trap Axis in Chronic Diseases.Journal of innate immunity · 2022Review
- New insights into the mechanisms of age-related protein-protein crosslinking in the human lens.Experimental eye research · 2021Review
- PAD4 takes charge during neutrophil activation: Impact of PAD4 mediated NET formation on immune-mediated disease.Journal of thrombosis and haemostasis : JTH · 2021Review
- Article
- Deimination, Intermediate Filaments and Associated Proteins.International journal of molecular sciences · 2020Review
- An interplay of structure and intrinsic disorder in the functionality of peptidylarginine deiminases, a family of key autoimmunity-related enzymes.Cellular and molecular life sciences : CMLS · 2019Review
- Thioredoxin Modulates Protein Arginine Deiminase 4 (PAD4)-Catalyzed Citrullination.Frontiers in immunology · 2019Article
Corrections and comments
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Authors and funding
3 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Protein citrullination catalyzed by peptidyl arginine deiminase (PADs) is involved in autoimmune disease pathogenesis, especially in rheumatoid arthritis. Calcium is a key regulator of PAD activity, but under normal physiological conditions it remains uncertain how intracellular calcium levels can be raised to sufficiently high levels to activate these enzymes. In pursuit of trying to identify other factors that influence PAD activity, we identified bicarbonate as a potential regulator of PAD activity. We demonstrate that physiological levels of bicarbonate upregulate citrullination by recombinant PAD2/4 and endogenous PADs in neutrophils. The impact of bicarbonate is independent of calcium and pH. Adding bicarbonate to commercial PAD activity kits could increase assay performance and biological relevance. These results suggest that citrullination activity is regulated by multiple factors including calcium and bicarbonate. We also provide commentary on the current understanding of PAD regulation and future perspective of research in this area.
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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.