Skip Navigation


Journal of Biochemistry Advance Access originally published online on June 26, 2008
Journal of Biochemistry 2008 144(3):393-398; doi:10.1093/jb/mvn079
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
144/3/393    most recent
mvn079v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Request Permissions
Google Scholar
Right arrow Articles by Nakayama-Hamada, M.
Right arrow Articles by Yamamoto, K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Nakayama-Hamada, M.
Right arrow Articles by Yamamoto, K.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© 2008 The Japanese Biochemical Society

Citrullinated Fibrinogen Inhibits Thrombin-catalysed Fibrin Polymerization

Makiko Nakayama-Hamada1,*, Akari Suzuki2,{dagger}, Hidehiko Furukawa1, Ryo Yamada2,3 and Kazuhiko Yamamoto2,4

1Daiichi-Sankyo Co., Ltd., 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710; 2Laboratory for Rheumatic Diseases, Center for Genomic Medicine, The Institute of Physical and Chemical Research, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045; 3Laboratory of Functional Genomics and Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639; and 4Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan

{dagger}To whom correspondence should be addressed. Tel: +81-45-503-9569, Fax: +81-45-503-9590, E-mail: akaris{at}src.riken.jp

Received April 2, 2008; Accepted May 30, 2008


  Abstract

Citrullination is the post-translational modification of arginine residues by peptidylarginine deiminases (PADIs). Fibrinogen is one substrate of PADIs under physiological conditions. Fibrinogen is an important factor for blood coagulation and inducing inflammation. The citrullinated form of fibrinogen appears in rheumatoid arthritis synovial tissue together with the production of autoantibodies that target self-peptides containing citrulline. However, whether the function of fibrinogen changes after citrullination remains unclear. We found that citrullinated fibrinogen markedly impairs the function of thrombin-catalysed fibrin polymerization and also inhibits fibrin formation. Increased citrullinated fibrinogen might thus affect the balance between coagulation and fibrinolysis and alter antigenicity under physiological conditions. These data suggest that citrullination of proteins could physiologically change functions and subsequently generate pro-inflammatory conditions and autoimmune reactions.

Key Words: autoantigen, citrullination, fibrinogen, fibrin formation, thrombin

Abbreviations: Cit, citrulline; DTT, dithiothreitol; EDTA, ethylenediaminetetraacetic acid; FPA, fibrinopeptide A; HPLC, high-performance liquid chromatography; Ig, immunoglobulin; PADI, peptidylarginine deiminase; PAGE, polyacrylamide gel electrophoresis; PVDF, polyvinylidene difluoride; RA, rheumatoid arthritis; SDS, sodium dodecyl sulfate

*These two authors contributed equally to this work


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.