Cadmium nanoparticles citrullinate cytokeratins within lung epithelial cells: cadmium as a potential cause of citrullination in chronic obstructive pulmonary disease.

Abstract

Objective:

The objective of the study was to determine whether the cadmium-derived materials induce intracellular protein citrullination.

Methods:

Human A549 lung epithelial cells were exposed to cadmium in soluble and nanoparticulate forms represented by cadmium chloride (CdCl2) and cadmium oxide (CdO), respectively, and their combinations with ultrafine carbon black (ufCB) produced by high temperature combustion, imitating cigarette burning. Protein citrullination in cell lysates was analyzed by Western immunoblotting and verified by immunofluorescent confocal microscopy. Target citrullinated proteins were identified by proteomic analysis.

Results:

CdO, ufCB and its combination with CdCl2 and CdO after high temperature combustion induced protein citrullination in cultured human lung epithelial cells, as detected by immunoblotting with anti-citrullinated protein antibody. Cytokeratins of type II (1, 2, 5, 6A, 6B and 77) and type I (9, 10) were identified as major intracellular citrullination targets. Immunofluorescent staining confirmed the localization of citrullinated proteins both in the cytoplasm and cell nuclei.

Conclusion:

Cadmium oxide nanoparticle exposure facilitated post-translational citrullination of proteins.

• Authors: David Hutchinson, Judith Müller, Joseph E McCarthy, Yurii K Gun'ko, Navin Kumar Verma, Xuezhi Bi, Luisana Di Cristo, Laura Kickham, Dania Movia, Adriele Prina-Mello, Yuri Volkov
• Journal: International journal of chronic obstructive pulmonary disease (Int J Chron Obstruct Pulmon Dis) Vol. 13 Pg. 441-449 ( 2018) ISSN: 1178-2005 [Electronic] New Zealand
• PMID: 29430177 (Publication Type: Journal Article)

Chemical References

• Cadmium Compounds
• Oxides
• cadmium oxide
• Citrulline
• Keratins
• Cadmium Chloride

Topics

• A549 Cells
• Cadmium Chloride (toxicity)
• Cadmium Compounds (toxicity)
• Citrullination
• Citrulline (metabolism)
• Epithelial Cells (drug effects, metabolism, pathology)
• Humans
• Keratins (metabolism)
• Lung (drug effects, metabolism, pathology)
• Metal Nanoparticles (toxicity)
• Oxides (toxicity)
• Protein Processing, Post-Translational (drug effects)
• Pulmonary Disease, Chronic Obstructive (chemically induced, metabolism, pathology)
• Risk Assessment
• Smoking (adverse effects)