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Citrullination of proteins: a common posttranslational modification pathway induced by different nanoparticles in vitro and in vivo.
Mohamed BM; Verma NK; Davies AM; McGowan A; Staunton KC; Prina-Mello A; Kelleher D; Botting CH; Causey CP; Thompson PR; Pruijn GJ; Kisin ER; Tkach AV; Shvedova AA; Volkov Y
Nanomed 2012 Aug; 7(8):1181-1195
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.
Nanotechnology; Immune-reaction; Immune-system; Immunology; Proteins; Protein-biosynthesis; Protein-biochemistry; In-vivo-studies; In-vitro-studies; Cellular-reactions; Cellular-function; Author Keywords: autoimmunity; high content analysis; immune system; inflammation; nanomaterial; nanoparticle; peptidylargininedeiminase; post-translational modification; protein citrullination; rheumatoid arthritis
Anna A Shvedova, Health Effects Laboratory Division, NIOSH, Morgantown, WV, USA
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