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

蛋白质瓜氨酸化:不同纳米粒子在体内和体外诱导的常见翻译后修饰途径

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作者: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 Jm Pruijn, Elena R Kisin, Alexey V Tkach, Anna A Shvedova, Yuri Volkov

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 &

Conclusion

Nanoparticle exposure facilitated post-translational citrullination of proteins.

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.

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