Citrullination of proteins: a common post-translational modification pathway induced by different nanoparticles in vitro and in vivo.
Department of Biochemistry and Molecular Pharmacology
Animals; Calcium; Carbon; Cell Line; Citrulline; Female; Humans; Hydrolases; Lung; Mice; Mice, Inbred C57BL; Nanostructures; Nanotubes, Carbon; Protein Processing, Post-Translational; Proteins; Silicon Dioxide; Soot
Biochemistry | Enzymes and Coenzymes | Medicinal-Pharmaceutical Chemistry | Nanomedicine | Therapeutics
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 and 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.
DOI of Published Version
Nanomedicine (Lond). 2012 Aug;7(8):1181-95. doi: 10.2217/nnm.11.177. Link to article on publisher's site
Nanomedicine (London, England)
Mohamed, Bashir M.; Verma, Navin K.; Davies, Anthony M.; McGowan, Aoife; Crosbie-Staunton, Kieran; Prina-Mello, Adriele; Kelleher, Dermot; Botting, Catherine H.; Causey, Corey P.; Thompson, Paul R.; Pruijn, Ger Jm; Kisin, Elena R.; Tkach, Alexey V.; Shvedova, Anna A.; and Volkov, Yuri, "Citrullination of proteins: a common post-translational modification pathway induced by different nanoparticles in vitro and in vivo." (2012). Thompson Lab Publications. 34.