Sarah Triboulet
Study of the effects of two types of metal nanoparticles on murine macrophages by a proteomic approach
Published on 11 October 2013
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Thesis presented October 11, 2013
Abstract :
Metallic nanoparticles (NPs) are more and more widely used, from industrial processes to biomedical research. However, data on their potential toxicity towards organisms are still lacking, especially regarding molecular mechanisms. It has been proven that some inorganic particles can lead to diseases when tissues are chronically exposed. In the case of pulmonary silicosis and asbestosis, induced by silica particles and asbestos fibers, chronic inflammation through alveolar macrophages is responsible for the disease. Indeed, macrophages are the first defense against exogenous attacks, like pathogens or inorganic compounds, which are eliminated through phagocytosis and inflammatory processes that are part of the innate immune response. Thus, this study aimed at analyzing the molecular effects of both copper- and zinc-based NPs (Cu/Cuo and ZnO) on murine macrophages cell lines. To this end, a reproducible proteomic-based approach using 2D electrophoresis and mass spectrometry was used. The proteomic data were validated using targeted approaches on both cell lines and primary macrophages. Our results show that both NPs exert similar high cytotoxicity, but the molecular responses are markedly different. Copper-based NPs strongly induce oxidative stress as well as alterations in mitochondrial metabolism, phagocytosis, and inflammatory mediators' production. These effects seem to be mostly related to the redox properties of copper, and are specific to the NP form. Conversely, zinc induced limited effects on the same processes, thus leading to no significant alterations in macrophages' immune functions. These effects are not NP-specific, since Zn2+ ions seem to exert most of them, probably due to their ability to interact with numbers of proteins, slightly altering their normal functions, and eventually leading only to cell death without prior functional alterations. This study allowed us to highlight some molecular mechanisms of both NP's toxicity.
Keywords:
Metallic nanoparticles (NPs), proteomic, Cu/Cuo, ZnO, 2D electrophoresis, mass spectrometry
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