Proteomics in mechanistic toxicology: History, concepts, achievements, caveats, and potential

Abstract

Toxicoproteomics can be defined as the application of proteomic approaches to the understanding of toxicology problems, and this review deals with the various types of applications that have been described in the literature. Toxicoproteomics has been applied to very different classes of toxicants, from drugs and natural products to metals, or from industrial chemicals to nanoparticles and nanofibers. It has also been applied to address questions at different levels, from the search of the primary molecular targets of toxicants to the deciphering of the molecular responses of cells and tissues to toxicants. Although restricted to mammalian cells and tissues, this paper reviews these two levels of investigation and the different application areas of toxicoproteomics, leading to the discussion of the advantages and drawbacks of the most popular proteomic platforms. Some of the pending questions in toxicoproteomics are also critically addressed, such as the specificity, validation, and result hierarchization issues. The question of shared mechanisms, which are encountered in many toxicoproteomic papers dealing with different toxicants, is also discussed. Finally, the future of toxicoproteomics is briefly outlined.

Molecular responses of alveolar epithelial A549 cells to chronic exposure to titanium dioxide nanoparticles: A proteomic view

“…The rationale for using epithelial alveolar cells in this study is that, due to their physicochemical properties, NPs are prone to deposit in the alveolar region of the lung [2,17]. We used 2D-gel proteomics to achieve this goal, because this technique investigates changes in protein abundances on a large scale, thereby providing a wider and untargeted view of the cellular functions impacted by biological stimuli of interest [18] while keeping the analysis at the protein level and not only at the peptide level. To the best of our knowledge, proteomics have never been used to assess cell response to a chronic exposure to TiO 2 -NPs.…”

A combined proteomic and targeted analysis unravels new toxic mechanisms for zinc oxide nanoparticles in macrophages

“…Proteomics studies are rather uncommon in the field of nanotoxicology [24], although recent studies have investigated the effects of silver nanoparticles on colon cell lines [25] or of copper oxide on lung epithelial cells [26]. Despite their relatively scarce use, all proteomic studies have shown a potential to unravel interesting cellular responses, e.g.…”

Methylmercury Induced Neurotoxicity and the Influence of Selenium in the Brains of Adult Zebrafish (Danio rerio)

“…Proteomics analysis followed by functional and pathway analysis can generate new insights into cellular pathways and functions affected by different classes of toxicants, including metals [21]. For example, quantitative intact proteomics in Atlantic cod ( Gadus morhua ) brain highlighted mitochondrial dysfunction, oxidative stress, and altered calcium homeostasis as key target mechanisms of MeHg-induced neurotoxicity [11].…”