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Molecular responses of mouse macrophages to copper and copper oxide nanoparticles inferred from proteomic analyses.

ABSTRACT: The molecular responses of macrophages to copper-based nanoparticles have been investigated via a combination of proteomic and biochemical approaches, using the RAW264.7 cell line as a model. Both metallic copper and copper oxide nanoparticles have been tested, with copper ion and zirconium oxide nanoparticles used as controls. Proteomic analysis highlighted changes in proteins implicated in oxidative stress responses (superoxide dismutases and peroxiredoxins), glutathione biosynthesis, the actomyosin cytoskeleton, and mitochondrial proteins (especially oxidative phosphorylation complex subunits). Validation studies employing functional analyses showed that the increases in glutathione biosynthesis and in mitochondrial complexes observed in the proteomic screen were critical to cell survival upon stress with copper-based nanoparticles; pharmacological inhibition of these two pathways enhanced cell vulnerability to copper-based nanoparticles, but not to copper ions. Furthermore, functional analyses using primary macrophages derived from bone marrow showed a decrease in reduced glutathione levels, a decrease in the mitochondrial transmembrane potential, and inhibition of phagocytosis and of lipopolysaccharide-induced nitric oxide production. However, only a fraction of these effects could be obtained with copper ions. In conclusion, this study showed that macrophage functions are significantly altered by copper-based nanoparticles. Also highlighted are the cellular pathways modulated by cells for survival and the exemplified cross-toxicities that can occur between copper-based nanoparticles and pharmacological agents.

SUBMITTER: Triboulet S

PROVIDER: S-EPMC3820927 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature

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Molecular responses of mouse macrophages to copper and copper oxide nanoparticles inferred from proteomic analyses.

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

Molecular & cellular proteomics : MCP 20130723 11

The molecular responses of macrophages to copper-based nanoparticles have been investigated via a combination of proteomic and biochemical approaches, using the RAW264.7 cell line as a model. Both metallic copper and copper oxide nanoparticles have been tested, with copper ion and zirconium oxide nanoparticles used as controls. Proteomic analysis highlighted changes in proteins implicated in oxidative stress responses (superoxide dismutases and peroxiredoxins), glutathione biosynthesis, the acto ...[more]

PMID: 23882024

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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.

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Molecular responses of mouse macrophages to copper and copper oxide nanoparticles inferred from proteomic analyses.

Publications

Molecular responses of mouse macrophages to copper and copper oxide nanoparticles inferred from proteomic analyses.

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