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Comparative proteomic analysis of the molecular responses of mouse macrophages to titanium dioxide and copper oxide nanoparticles unravels some toxic mechanisms for copper oxide nanoparticles in macrophages.

ABSTRACT: Titanium dioxide and copper oxide nanoparticles are more and more widely used because of their catalytic properties, of their light absorbing properties (titanium dioxide) or of their biocidal properties (copper oxide), increasing the risk of adverse health effects. In this frame, the responses of mouse macrophages were studied. Both proteomic and targeted analyses were performed to investigate several parameters, such as phagocytic capacity, cytokine release, copper release, and response at sub toxic doses. Besides titanium dioxide and copper oxide nanoparticles, copper ions were used as controls. We also showed that the overall copper release in the cell does not explain per se the toxicity observed with copper oxide nanoparticles. In addition, both copper ion and copper oxide nanoparticles, but not titanium oxide, induced DNA strands breaks in macrophages. As to functional responses, the phagocytic capacity was not hampered by any of the treatments at non-toxic doses, while copper ion decreased the lipopolysaccharide-induced cytokine and nitric oxide productions. The proteomic analyses highlighted very few changes induced by titanium dioxide nanoparticles, but an induction of heme oxygenase, an increase of glutathione synthesis and a decrease of tetrahydrobiopterin in response to copper oxide nanoparticles. Subsequent targeted analyses demonstrated that the increase in glutathione biosynthesis and the induction of heme oxygenase (e.g. by lovastatin/monacolin K) are critical for macrophages to survive a copper challenge, and that the intermediates of the catecholamine pathway induce a strong cross toxicity with copper oxide nanoparticles and copper ions.

SUBMITTER: Triboulet S

PROVIDER: S-EPMC4406518 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Comparative proteomic analysis of the molecular responses of mouse macrophages to titanium dioxide and copper oxide nanoparticles unravels some toxic mechanisms for copper oxide nanoparticles in macrophages.

Triboulet Sarah S Aude-Garcia Catherine C Armand Lucie L Collin-Faure Véronique V Chevallet Mireille M Diemer Hélène H Gerdil Adèle A Proamer Fabienne F Strub Jean-Marc JM Habert Aurélie A Herlin Nathalie N Van Dorsselaer Alain A Carrière Marie M Rabilloud Thierry T

PloS one 20150422 4

Titanium dioxide and copper oxide nanoparticles are more and more widely used because of their catalytic properties, of their light absorbing properties (titanium dioxide) or of their biocidal properties (copper oxide), increasing the risk of adverse health effects. In this frame, the responses of mouse macrophages were studied. Both proteomic and targeted analyses were performed to investigate several parameters, such as phagocytic capacity, cytokine release, copper release, and response at sub ...[more]

PMID: 25902355

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Project description:Changes in tissue transcriptomes and productivity of Arabidopsis thaliana were investigated during exposure of plants to 2 widely used engineered metal oxide nanoparticles, titanium dioxide (nano-titania) and cerium dioxide (nano-ceria). Microarray analyses confirmed that exposure to either nanoparticle altered the transcriptomes of rosette leaves and roots, with comparatively larger numbers of differentially expressed genes found under nano-titania exposure. Nano-titania induced more differentially expressed genes in rosette leaves, whereas roots had more differentially expressed genes under nano-ceria exposure. MapMan analyses indicated that although nano-titania up-regulated overall metabolism in both tissues, metabolic processes under nano-ceria remained mostly unchanged. Gene enrichment analysis indicated that both nanoparticles mainly enriched ontology groups such as responses to stress (abiotic and biotic), and defense responses (pathogens), and responses to endogenous stimuli (hormones). Nano-titania specifically induced genes associated with photosynthesis, whereas nano-ceria induced expression of genes related to activating transcription factors, most notably those belonging to the ethylene responsive element binding protein family. Interestingly, there were also increased numbers of rosette leaves and plant biomass under nano-ceria exposure, but not under nano-titania. Other transcriptomic responses did not clearly relate to responses observed at the organism level, possibly because of functional and genomic redundancy in Arabidopsis, which may mask expression of morphological changes, despite discernable responses at the transcriptome level. In addition, transcriptomic changes often relate to transgenerational phenotypic development, and hence it may be productive to direct further experimental work to integrate high-throughput genomic results with longer term changes in subsequent generations. Environ Toxicol Chem 2017;36:71-82. Published 2016 Wiley Periodicals Inc. on behalf of SETAC. This article is a US government work and, as such, is in the public domain in the United States of America.

Dataset Information

Comparative proteomic analysis of the molecular responses of mouse macrophages to titanium dioxide and copper oxide nanoparticles unravels some toxic mechanisms for copper oxide nanoparticles in macrophages.

Publications

Comparative proteomic analysis of the molecular responses of mouse macrophages to titanium dioxide and copper oxide nanoparticles unravels some toxic mechanisms for copper oxide nanoparticles in macrophages.

Similar Datasets

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