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

镉纳米粒子在肺上皮细胞内瓜氨酸化细胞角蛋白:镉是慢性阻塞性肺病中瓜氨酸化的潜在原因

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作者: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

Conclusion

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

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.

Objective

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

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.

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