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

Details

• Personal Author:
  Botting CH ; Causey CP ; Davies AM ; Kelleher D ; Kisin ER ; McGowan A ; Mohamed BM ; Prina-Mello A ; Pruijn GJ ; Shvedova AA ; Staunton KC ; Thompson PR ; Tkach AV ; Verma NK ; Volkov Y
• Description:
  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. [Description provided by NIOSH]
• Subjects:
  Immune System Occupational Health Safety
• Keywords:
  Author Keywords: Autoimmunity Cellular-function Cellular-reactions High Content Analysis Immune-reaction Immune-system Immune System Immunology In-vitro-studies In-vivo-studies Inflammation Nanomaterial Nanoparticle Nanotechnology Peptidylargininedeiminase Post-translational Modification Protein-biochemistry Protein-biosynthesis Protein Citrullination Proteins Rheumatoid Arthritis

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• ISSN:
  1743-5889
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  OSHA Region 3 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  7
• Issue:
  8
• NIOSHTIC Number:
  nn:20040892
• Citation:
  Nanomed 2012 Aug; 7(8):1181-1195
• Contact Point Address:
  Anna A Shvedova, Health Effects Laboratory Division, NIOSH, Morgantown, WV, USA
• Email:
  ats1@cdc.gov
• CAS Registry Number:
  Carbon black (CAS RN 1333-86-4) ; Silica (CAS RN 7631-86-9)
• Federal Fiscal Year:
  2012
• NORA Priority Area:
  Manufacturing
• Peer Reviewed:
  True
• Source Full Name:
  Nanomedicine
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:12a6f753d22153fc44d855bcfd1f51ff31d3ee6aaaf1bf92a1b24e95ef903a0ae5bf7a4096e1df3206adc9f39320c5816129c9269f500462740837458afc24a9
• Download URL:
  https://stacks.cdc.gov/view/cdc/193594/cdc_193594_DS1.pdf
• File Type:
  [PDF - 5.16 MB ]