title: Citrullination of proteins: a common post-translational modification pathway induced by different nanoparticles in vitro and in vivo.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  Nanoparticle exposure facilitated post-translational citrullination of proteins.
authors.affiliation: Department of Clinical Medicine, Trinity College Dublin, Ireland.
authors.forename: Bashir M
authors.initials: BM
authors.lastname: Mohamed
authors.forename: Navin K
authors.initials: NK
authors.lastname: Verma
authors.forename: Anthony M
authors.initials: AM
authors.lastname: Davies
authors.forename: Aoife
authors.initials: A
authors.lastname: McGowan
authors.forename: Kieran
authors.initials: K
authors.lastname: Crosbie-Staunton
authors.forename: Adriele
authors.initials: A
authors.lastname: Prina-Mello
authors.forename: Dermot
authors.initials: D
authors.lastname: Kelleher
authors.forename: Catherine H
authors.initials: CH
authors.lastname: Botting
authors.forename: Corey P
authors.initials: CP
authors.lastname: Causey
authors.forename: Paul R
authors.initials: PR
authors.lastname: Thompson
authors.forename: Ger Jm
authors.initials: GJ
authors.lastname: Pruijn
authors.forename: Elena R
authors.initials: ER
authors.lastname: Kisin
authors.forename: Alexey V
authors.initials: AV
authors.lastname: Tkach
authors.forename: Anna A
authors.initials: AA
authors.lastname: Shvedova
authors.forename: Yuri
authors.initials: Y
authors.lastname: Volkov
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002244:Carbon / Q000008:administration & dosage / Q000378:metabolism*; D002460:Cell Line; D002956:Citrulline / Q000378:metabolism*; D005260:Female; D006801:Humans; D006867:Hydrolases / Q000037:antagonists & inhibitors / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D049329:Nanostructures / Q000008:administration & dosage* / Q000737:chemistry; D037742:Nanotubes, Carbon / Q000737:chemistry; D011499:Protein Processing, Post-Translational; D000076342:Protein-Arginine Deiminases; D011506:Proteins / Q000378:metabolism*; D012822:Silicon Dioxide / Q000008:administration & dosage / Q000378:metabolism*; D053260:Soot / Q000008:administration & dosage / Q000378:metabolism*
chemical_list: D037742:Nanotubes, Carbon; D011506:Proteins; D053260:Soot; D002956:Citrulline; D002244:Carbon; D012822:Silicon Dioxide; D006867:Hydrolases; D000076342:Protein-Arginine Deiminases; D002118:Calcium