Citrullination of proteins: a common post-translational modification pathway induced by different nanoparticles in vitro and in vivo. (August 2012)

• Record Type: Journal Article
• Authors: Mohamed, Bashir M; Verma, Navin K; Davies, Anthony M; McGowan, Aoife; Crosbie-Staunton, Kieran; Prina-Mello, Adriele; Kelleher, Dermot; Botting, Catherine H; Causey, Corey P; Thompson, Paul R; Pruijn, Ger JM; Kisin, Elena R; Tkach, Alexey V; Shvedova, Anna A; Volkov, Yuri
• Is Part Of: Nanomedicine. Volume 7:Number 8(2012)
• Page Start: 1181
• Page End: 1195
• Publication Date: 2012-08
• Subjects: autoimmunity -- high content analysis -- immune system -- inflammation -- nanomaterial -- nanoparticle -- peptidylargininedeiminase -- post-translational modification -- protein citrullination -- rheumatoid arthritis; Nanotechnology -- Periodicals; Medical technology -- Periodicals; Nanotechnology -- Therapeutic use -- Periodicals; 610.28
• DOI: 10.2217/nnm.11.177
• Languages: English
• ISSNs: 1743-5889

Abstract

Aim: Rapidly expanding manufacture and use of nanomaterials emphasize the requirements for thorough assessment of health outcomes associated with novel applications. Post-translational protein modifications catalyzed by Ca 2+ -dependent peptidylargininedeiminases have been shown to trigger immune responses including autoantibody generation, a hallmark of immune complexes deposition in rheumatoid arthritis. Therefore, the aim of the study was to assess if nanoparticles are able to promote protein citrullination.Materials & methods: Human A549 and THP-1 cells were exposed to silicon dioxide, carbon black or single-walled carbon nanotubes. C57BL/6 mice were exposed to respirable single-walled carbon nanotubes. Protein citrullination, peptidylargininedeiminases activity and target proteins were evaluated.Results: The studied nanoparticles induced protein citrullination both in cultured human cells and mouse lung tissues. Citrullination occurred via the peptidylargininedeiminase-dependent mechanism. Cytokeratines 7, 8, 18 and plectins were identified as intracellular citrullination targets.Conclusion: Nanoparticle exposure facilitated post-translational citrullination of proteins. Original submitted 18 March 2011; Revised submitted 10 November 2011; Published online 25 May 2012