Proteomics as a tool for examining the toxicity of heavy metals

Luque-García, José L.; Cabezas-Sánchez, Pablo; Cámara, Carmen

doi:10.1016/j.trac.2011.01.014

Cited by 48 publications

(28 citation statements)

References 101 publications

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“…Very few studies have used the analytical power of proteomics to go deeper into the mechanisms of the response to nanoparticles or metals (reviewed in Ref. 18). A few exceptions are studies on, for example, carbon-based nanoparticles (19) and titanium dioxide (20,21).…”

Section: Teins (Especially Oxidative Phosphorylation Complex Subunitsmentioning

confidence: 99%

Molecular Responses of Mouse Macrophages to Copper and Copper Oxide Nanoparticles Inferred from Proteomic Analyses

Triboulet

Aude-Garcia

Carrière

et al. 2013

Molecular & Cellular Proteomics

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The molecular responses of macrophages to copperbased 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 crosstoxicities that can occur between copper-based nanoparticles and pharmacological agents. Molecular & Cellular

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Section: Teins (Especially Oxidative Phosphorylation Complex Subunitsmentioning

confidence: 99%

Molecular Responses of Mouse Macrophages to Copper and Copper Oxide Nanoparticles Inferred from Proteomic Analyses

Triboulet

Aude-Garcia

Carrière

et al. 2013

Molecular & Cellular Proteomics

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“…Among all the proteomic approaches available, quantitative strategies are particularly attractive, since they allow for identification of differentially expressed proteins by comparing proteomes as affected by different conditions [9]. In this way, the identification of changes in individual proteins or group of proteins associated with SeNPs exposure could help to gain insight into the mechanisms of action of these NPs.…”

Section: Introductionmentioning

confidence: 99%

Effect of Chitosan-Stabilized Selenium Nanoparticles on Cell Cycle Arrest and Invasiveness in Hepatocarcinoma Cells Revealed by Quantitative Proteomics

Heras¹

2014

J Nanomed Nanotechnol

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Selenium nanoparticles have been recently proposed as a potential chemotherapeutic agent due to its low toxicity and its ability to arrest the cell cycle of cancer cells. However, the biochemical mechanisms associated to this effect have not yet been uncovered. We evaluate here the potential of chitosan-stabilized selenium nanoparticles to induce cell cycle arrest and to inhibit in-vitro invasiveness in HepG2 cells. In addition, we use a quantitative proteomic approach to identify potential protein targets involved in the mechanisms associated to selenium nanoparticles exposure. Our data suggest that the induction of the cell cycle arrest at the S phase is mediated by de-regulation of the eIF3 protein complex. We found additional de-regulated proteins upon selenium nanoparticles exposure that could also be involved in the overall inhibition of cell proliferation. These findings not only support the potential of chitosan-stabilized selenium nanoparticles as anti-cancer therapy but also provide a deeper insight into the mechanisms associated to their chemotherapeutic effects.

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“…Most of the studies carried out so far to evaluate heavy-metal toxicity have focused on both: (a) the development of analytical methods for determination of the toxic species in different samples such as contaminated soils, water, plant, and animal tissues [1,2], mainly using techniques for elemental analysis, and (b) the study of the effects of the toxic species on the environment and ultimately on human health. However, the cellular mechanisms underlying heavy-metal toxicity and the way in which toxic metals interact with living organisms [3] at the molecular level are still not fully understood. Among heavy metals, methylmercury (MeHg) represents a well-known risk to human health.…”

Section: Introductionmentioning

confidence: 99%

Differential protein expression of hepatic cells associated with MeHg exposure: deepening into the molecular mechanisms of toxicity

et al. 2012

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Understanding the molecular mechanisms underlying MeHg toxicity and the way in which this molecule interacts with living organisms is a critical point since MeHg represents a well-known risk to ecosystems and human health. We used a quantitative proteomic approach based on stable isotopic labeling by amino acids in cell culture in combination with SDS-PAGE and nanoflow LC-ESI-LTQ for analyzing the differential protein expression of hepatic cells associated to MeHg exposure. Seventy-eight proteins were found de-regulated by more than 1.5-fold. We identified a number of proteins involved in different essential biological processes including apoptosis, mitochondrial dysfunction, cellular trafficking and energy production. Among these proteins, we found several molecules whose de-regulation has been already related to MeHg exposure, thus confirming the usefulness of our discovery approach, and new ones that helped to gain a deeper insight into the biomolecular mechanisms related to MeHg-induced toxicity. Overexpression of several HSPs and the proteasome 26S subunit itself showed the proteasome system as a molecular target of toxic MeHg. As for the interaction networks, the top ranked was the nucleic acid metabolism, where many of the identified de-regulated proteins are involved.

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Proteomics as a tool for examining the toxicity of heavy metals

Cited by 48 publications

References 101 publications

Molecular Responses of Mouse Macrophages to Copper and Copper Oxide Nanoparticles Inferred from Proteomic Analyses

Molecular Responses of Mouse Macrophages to Copper and Copper Oxide Nanoparticles Inferred from Proteomic Analyses

Effect of Chitosan-Stabilized Selenium Nanoparticles on Cell Cycle Arrest and Invasiveness in Hepatocarcinoma Cells Revealed by Quantitative Proteomics

Differential protein expression of hepatic cells associated with MeHg exposure: deepening into the molecular mechanisms of toxicity

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