dc.contributor.author | Manganelli, V | |
dc.contributor.author | Recalchi, S | |
dc.contributor.author | Capozzi, A | |
dc.contributor.author | Riitano, G | |
dc.contributor.author | Mattei, V | |
dc.contributor.author | Longo, A | |
dc.contributor.author | Di Franco, M | |
dc.contributor.author | Alessandri, C | |
dc.contributor.author | Bombardieri, M | |
dc.contributor.author | Valesini, G | |
dc.contributor.author | Misasi, R | |
dc.contributor.author | Garofalo, T | |
dc.contributor.author | Sorice, M | |
dc.date.accessioned | 2020-08-19T15:12:28Z | |
dc.date.available | 2020-08-19T15:12:28Z | |
dc.date.issued | 2018-11-01 | |
dc.identifier.citation | Manganelli V, Recalchi S, Capozzi A, et al. Autophagy induces protein carbamylation in fibroblast-like synoviocytes from patients with rheumatoid arthritis. Rheumatology (Oxford). 2018;57(11):2032-2041. doi:10.1093/rheumatology/key174 | en_US |
dc.identifier.uri | https://qmro.qmul.ac.uk/xmlui/handle/123456789/66434 | |
dc.description.abstract | Objectives: Autophagy is a homeostatic and physiological process that promotes the turnover of proteins and organelles damaged in conditions of cellular stress. We previously demonstrated that autophagy represents a key processing event creating a substrate for autoreactivity, which is involved in post-translational changes and generation of citrullinated peptides, recognized by the immune system in RA. In this study, we analysed whether autophagy is involved in other post-translational changes that can generate autoantigens, focusing on carbamylation processes. Carbamylation is a nonenzymatic post-translational modification, in which homocitrulline is generated by the reaction of cyanate with the primary amine of lysine residues; carbamylated peptides may accumulate during inflammation conditions. Methods: The role of autophagy in the generation of carbamylated proteins was evaluated in vitro in fibroblasts as well as in synoviocytes from RA patients, treated with 5 μM tunicamycin or 200 nM rapamycin; the correlation between autophagy and carbamylated proteins was analysed in mononuclear cells from 30 naïve early-active RA patients. Results: Our results demonstrated that cells treated with tunicamycin or rapamycin showed a significant increase of carbamylated proteins. Immunoblotting and immunoprecipitation experiments identified vimentin as the main carbamylated protein. Furthermore, a correlation was found between autophagy and carbamylation levels in mononuclear cells of naïve RA patients. Conclusion: These data indicate that autophagy is able to induce in vitro carbamylation processes, and in vivo appears to be related to an increase in carbamylation during RA. These observations introduce a new pathogenetic mechanism of disease, which could contribute to more accurate monitoring of patients. | en_US |
dc.format.extent | 2032 - 2041 | |
dc.language | eng | |
dc.publisher | Oxford University Press | en_US |
dc.relation.ispartof | Rheumatology (Oxford) | |
dc.subject | Adult | en_US |
dc.subject | Arthritis, Rheumatoid | en_US |
dc.subject | Autophagy | en_US |
dc.subject | Cells, Cultured | en_US |
dc.subject | Female | en_US |
dc.subject | Humans | en_US |
dc.subject | Male | en_US |
dc.subject | Middle Aged | en_US |
dc.subject | Protein Carbamylation | en_US |
dc.subject | Synoviocytes | en_US |
dc.subject | Vimentin | en_US |
dc.title | Autophagy induces protein carbamylation in fibroblast-like synoviocytes from patients with rheumatoid arthritis. | en_US |
dc.type | Article | en_US |
dc.rights.holder | © 2018 Oxford University Press | |
dc.identifier.doi | 10.1093/rheumatology/key174 | |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/29982776 | en_US |
pubs.issue | 11 | en_US |
pubs.notes | Not known | en_US |
pubs.publication-status | Published | en_US |
pubs.publisher-url | http://doi.org/10.1093/rheumatology/key174 | |
pubs.volume | 57 | en_US |
rioxxterms.funder | Default funder | en_US |
rioxxterms.identifier.project | Default project | en_US |