دورية أكاديمية
The role of SERPIN citrullination in thrombosis
| العنوان: | The role of SERPIN citrullination in thrombosis |
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| المؤلفون: | Tilvawala, Ronak, Nemmara, Venkatesh V., Reyes, Archie C., Sorvillo, Nicoletta, Salinger, Ari J., Cherpokova, Deya, Fukui, Saeko, Gutch, Sarah, Wagner, Denisa, Thompson, Paul R |
| المساهمون: | Thompson Lab, Department of Biochemistry and Molecular Pharmacology |
| المصدر: | Cell chemical biology ; 28 ; 12 ; 1728-1739.e5 |
| سنة النشر: | 2022 |
| المجموعة: | University of Massachusetts, Medical School: eScholarship@UMMS |
| مصطلحات موضوعية: | citrullination, deep vein thrombosis, rheumatoid arthritis, serine protease inhibitors, Amino Acids, Peptides, and Proteins, Biochemical Phenomena, Metabolism, and Nutrition, Biochemistry, Biophysics, and Structural Biology, Cardiovascular Diseases, Enzymes and Coenzymes, Medicinal Chemistry and Pharmaceutics, Medicinal-Pharmaceutical Chemistry, Musculoskeletal Diseases |
| الوصف: | Aberrant protein citrullination is associated with many pathologies; however, the specific effects of this modification remain unknown. We have previously demonstrated that serine protease inhibitors (SERPINs) are highly citrullinated in rheumatoid arthritis (RA) patients. These citrullinated SERPINs include antithrombin, antiplasmin, and t-PAI, which regulate the coagulation and fibrinolysis cascades. Notably, citrullination eliminates their inhibitory activity. Here, we demonstrate that citrullination of antithrombin and t-PAI impairs their binding to their cognate proteases. By contrast, citrullination converts antiplasmin into a substrate. We recapitulate the effects of SERPIN citrullination using in vitro plasma clotting and fibrinolysis assays. Moreover, we show that citrullinated antithrombin and antiplasmin are increased and decreased in a deep vein thrombosis (DVT) model, accounting for how SERPIN citrullination shifts the equilibrium toward thrombus formation. These data provide a direct link between increased citrullination and the risk of thrombosis in autoimmunity and indicate that aberrant SERPIN citrullination promotes pathological thrombus formation. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | Link to Article in PubMed; https://doi.org/10.1016/j.chembiol.2021.07.009Test; Tilvawala R, Nemmara VV, Reyes AC, Sorvillo N, Salinger AJ, Cherpokova D, Fukui S, Gutch S, Wagner D, Thompson PR. The role of SERPIN citrullination in thrombosis. Cell Chem Biol. 2021 Dec 16;28(12):1728-1739.e5. doi:10.1016/j.chembiol.2021.07.009. Epub 2021 Aug 4. PMID: 34352225; PMCID: PMC8688209. Link to article on publisher's site; 2451-9448 (Linking); http://hdl.handle.net/20.500.14038/29928Test; https://escholarship.umassmed.edu/faculty_pubs/2131Test; faculty_pubs/2131 |
| DOI: | 10.1016/j.chembiol.2021.07.009 |
| الإتاحة: | https://doi.org/10.1016/j.chembiol.2021.07.009Test https://doi.org/20.500.14038/29928Test https://hdl.handle.net/20.500.14038/29928Test https://escholarship.umassmed.edu/faculty_pubs/2131Test |
| رقم الانضمام: | edsbas.A2310BAA |
| قاعدة البيانات: | BASE |
| DOI: | 10.1016/j.chembiol.2021.07.009 |
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