Please use this identifier to cite or link to this item:
Title: Potential protein targets of the peptidylarginine deiminase 2 and peptidylarginine deiminase 4 enzymes in rheumatoid synovial tissue and its possible meaning
Authors: Badillo Soto, Martha Adriana
Rodríguez Rodríguez, Mayra
Pérez Pérez, María Elena
Daza Benitez, Leonel
Bollain y Goytia, Juan José
Carrillo Jimenez, Miguel Angel
Avalos Díaz, Esperanza del Refugio
Herrera Esparza, Rafael
Issue Date: 2016
Publisher: Aves
Abstract: Objective: The molecular mechanism of citrullination involves the calcium-dependent peptidylarginine deiminase (PAD) family of enzymes. These enzymes induce a stereochemical modification of normal proteins and transform them into autoantigens, which in rheumatoid arthritis trigger a complex cascade of joint inflammatory events followed by chronic synovitis, pannus formation, and finally, cartilage destruction. By hypothesizing that PAD2 and PAD4 enzymes produce autoantigens, we investigated five possible synovial protein targets of PAD enzymes. Material and Methods: We measured PAD2, PAD4, and citrullinated proteins in 10 rheumatoid and 10 osteoarthritis synovial biopsies and then assessed the post-translational modifications of fibrinogen, cytokeratin, tubulin, IgG, and vimentin proteins using a double-fluorescence assay with specific antibodies and an affinity-purified anti-citrullinated peptide (CCP) antibody. The degree of co-localization was analyzed, and statistical significance was determined by ANOVA, Fisher’s exact test, and regression analysis. Results: The principal results of this study demonstrated that citrullinated proteins, such as fibrinogen, IgG, and other probed proteins, were targets of PAD2 and PAD4 activity in rheumatoid synovial biopsies, whereas osteoarthritis biopsies were negative for this enzyme (p<0.0001). An analysis of citrullination sites using the UniProtKB/Swiss-Prot data bank predicts that the secondary structure of the analyzed proteins displays most of the sites for citrullination; a discussion regarding its possible meaning in terms of pathogenesis is made. Conclusion: Our results support the conclusion that the synovial citrullination of proteins is PAD2 and PAD4 dependent. Furthermore, there is a collection of candidate proteins that can be citrullinated.
ISSN: 2147-9720
Other Identifiers: info:eu-repo/semantics/publishedVersion
Appears in Collections:*Documentos Académicos*-- UA Medicina

Files in This Item:
File Description SizeFormat 
Potential protein targets.pdf1,56 MBAdobe PDFView/Open

This item is licensed under a Creative Commons License Creative Commons