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

UMMS Affiliation

Department of Biochemistry and Molecular Pharmacology

Publication Date


Document Type



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

Journal/Book/Conference Title

Nanomedicine (London, England)


At the time of publication, Paul Thompson was not yet affiliated with UMass Medical School.

Related Resources

Link to Article in PubMed