Citrullination of proteins: a common post-translational modification pathway induced by different nanoparticles in vitro and in vivo

Bashir M. Mohamed, Navin K. Verma, Anthony M. Davies, Aoife McGowan, Kieran Crosbie-Staunton, Adriele Prina-Mello, Dermot Kelleher, Catherine H. Botting, Corey P. Causey, Paul R. Thompson, Ger J. M. Pruijn, Elena R. Kisin, Alexey V. Tkach, Anna A. Shvedova, Yuri Volkov

Research output: Contribution to journalArticlepeer-review

81 Citations (Scopus)

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 Ca2+-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 languageEnglish
Pages (from-to)1181-1195
Number of pages15
JournalNanomedicine
Volume7
Issue number8
DOIs
Publication statusPublished - Aug 2012

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