Potential protein targets of the peptidylarginine deiminase 2 and peptidylarginine deiminase 4 enzymes in rheumatoid synovial tissue and its possible meaning
| Autor: | Juan José Bollain y Goytia, Miguel Angel Carrillo Jimenez, Leonel Daza Benitez, María Elena Pérez Pérez, Martha Adriana Badillo Soto, Esperanza Avalos Díaz, Mayra Rodríguez Rodríguez, Rafael Herrera Esparza |
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| Rok vydání: | 2015 |
| Předmět: |
030203 arthritis & rheumatology
0301 basic medicine chemistry.chemical_classification business.industry Citrullination medicine.disease 03 medical and health sciences 030104 developmental biology 0302 clinical medicine medicine.anatomical_structure Enzyme chemistry Biochemistry Pannus Formation Rheumatoid arthritis Peptidylarginine Deiminase Molecular mechanism Medicine Synovial membrane business Synovial tissue Original Investigation |
| Zdroj: | European journal of rheumatology. 3(2) |
| ISSN: | 2147-9720 |
| Popis: | 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.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.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 (p0.0001). 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.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. |
| Databáze: | OpenAIRE |
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