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

David Hutchinson,1,2 Judith Müller,3 Joseph E McCarthy,4 Yurii K Gun’ko,4,5 Navin Kumar Verma,6 Xuezhi Bi,7 Luisana Di Cristo,8 Laura Kickham,8 Dania Movia,8 Adriele Prina-Mello,5,8 Yuri Volkov5,8,9 1Royal Cornwall Hospital NHS Trust, Treliske, 2University of Exeter Medical Schoo...

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Main Authors: Hutchinson D, Müller J, McCarthy JE, Gun'ko YK, Verma NK, Bi X, Di Cristo L, Kickham L, Movia D, Prina-Mello A, Volkov Y
Format: Article
Language:English
Published: Dove Medical Press 2018-01-01
Series:International Journal of COPD
Subjects:
Online Access:https://www.dovepress.com/cadmium-nanoparticles--citrullinate-cytokeratins-within-lung-epithelia-peer-reviewed-article-COPD
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author Hutchinson D
Müller J
McCarthy JE
Gun'ko YK
Verma NK
Bi X
Di Cristo L
Kickham L
Movia D
Prina-Mello A
Volkov Y
author_facet Hutchinson D
Müller J
McCarthy JE
Gun'ko YK
Verma NK
Bi X
Di Cristo L
Kickham L
Movia D
Prina-Mello A
Volkov Y
author_sort Hutchinson D
collection DOAJ
description David Hutchinson,1,2 Judith Müller,3 Joseph E McCarthy,4 Yurii K Gun’ko,4,5 Navin Kumar Verma,6 Xuezhi Bi,7 Luisana Di Cristo,8 Laura Kickham,8 Dania Movia,8 Adriele Prina-Mello,5,8 Yuri Volkov5,8,9 1Royal Cornwall Hospital NHS Trust, Treliske, 2University of Exeter Medical School Cornwall, UK; 3University of Basel, Basel, Switzerland; 4School of Chemistry, 5Advanced Materials for BioEngineering Research Centre (AMBER), Trinity College Dublin, Dublin, Ireland; 6Lee Kong Chian School of Medicine, Nanyang Technological University, 7Bioprocessing Technology Institute, A*STAR Graduate Academy, Singapore; 8Department of Clinical Medicine, School of Medicine, Trinity College Dublin, Dublin, Ireland; 9International Laboratory of Magnetically Controlled Nanosystems for Theranostics of Oncological and Cardiovascular Diseases, ITMO University, St. Petersburg, Russia 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. Keywords: cadmium, COPD, nanoparticles, cytokeratins, citrullination, autoimmunity, proteomics
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spelling doaj.art-7775cb3b68d248b2a687faafc89b55d62022-12-22T03:45:32ZengDove Medical PressInternational Journal of COPD1178-20052018-01-01Volume 1344144936596Cadmium nanoparticles citrullinate cytokeratins within lung epithelial cells: cadmium as a potential cause of citrullination in chronic obstructive pulmonary diseaseHutchinson DMüller JMcCarthy JEGun'ko YKVerma NKBi XDi Cristo LKickham LMovia DPrina-Mello AVolkov YDavid Hutchinson,1,2 Judith Müller,3 Joseph E McCarthy,4 Yurii K Gun’ko,4,5 Navin Kumar Verma,6 Xuezhi Bi,7 Luisana Di Cristo,8 Laura Kickham,8 Dania Movia,8 Adriele Prina-Mello,5,8 Yuri Volkov5,8,9 1Royal Cornwall Hospital NHS Trust, Treliske, 2University of Exeter Medical School Cornwall, UK; 3University of Basel, Basel, Switzerland; 4School of Chemistry, 5Advanced Materials for BioEngineering Research Centre (AMBER), Trinity College Dublin, Dublin, Ireland; 6Lee Kong Chian School of Medicine, Nanyang Technological University, 7Bioprocessing Technology Institute, A*STAR Graduate Academy, Singapore; 8Department of Clinical Medicine, School of Medicine, Trinity College Dublin, Dublin, Ireland; 9International Laboratory of Magnetically Controlled Nanosystems for Theranostics of Oncological and Cardiovascular Diseases, ITMO University, St. Petersburg, Russia 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. Keywords: cadmium, COPD, nanoparticles, cytokeratins, citrullination, autoimmunity, proteomicshttps://www.dovepress.com/cadmium-nanoparticles--citrullinate-cytokeratins-within-lung-epithelia-peer-reviewed-article-COPDCadmiumCOPDnanoparticlescytokeratinscitrullination
spellingShingle Hutchinson D
Müller J
McCarthy JE
Gun'ko YK
Verma NK
Bi X
Di Cristo L
Kickham L
Movia D
Prina-Mello A
Volkov Y
Cadmium nanoparticles citrullinate cytokeratins within lung epithelial cells: cadmium as a potential cause of citrullination in chronic obstructive pulmonary disease
International Journal of COPD
Cadmium
COPD
nanoparticles
cytokeratins
citrullination
title Cadmium nanoparticles citrullinate cytokeratins within lung epithelial cells: cadmium as a potential cause of citrullination in chronic obstructive pulmonary disease
title_full Cadmium nanoparticles citrullinate cytokeratins within lung epithelial cells: cadmium as a potential cause of citrullination in chronic obstructive pulmonary disease
title_fullStr Cadmium nanoparticles citrullinate cytokeratins within lung epithelial cells: cadmium as a potential cause of citrullination in chronic obstructive pulmonary disease
title_full_unstemmed Cadmium nanoparticles citrullinate cytokeratins within lung epithelial cells: cadmium as a potential cause of citrullination in chronic obstructive pulmonary disease
title_short Cadmium nanoparticles citrullinate cytokeratins within lung epithelial cells: cadmium as a potential cause of citrullination in chronic obstructive pulmonary disease
title_sort cadmium nanoparticles citrullinate cytokeratins within lung epithelial cells cadmium as a potential cause of citrullination in chronic obstructive pulmonary disease
topic Cadmium
COPD
nanoparticles
cytokeratins
citrullination
url https://www.dovepress.com/cadmium-nanoparticles--citrullinate-cytokeratins-within-lung-epithelia-peer-reviewed-article-COPD
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