title: A redox proteomics approach to investigate the mode of action of nanomaterials.
abstract: Numbers of engineered nanomaterials (ENMs) are steadily increasing. Therefore, alternative testing approaches with reduced costs and high predictivity suitable for high throughput screening and prioritization are urgently needed to ensure a fast and effective development of safe products. In parallel, extensive research efforts are targeted to understanding modes of action of ENMs, which may also support the development of new predictive assays. Oxidative stress is a widely accepted paradigm associated with different adverse outcomes of ENMs. It has frequently been identified in in vitro and in vivo studies and different assays have been developed for this purpose. Fluorescent dye based read-outs are most frequently used for cell testing in vitro but may be limited due to possible interference of the ENMs. Recently, other assays have been put forward such as acellular determination of ROS production potential using methods like electron spin resonance, antioxidant quantification or the use of specific sensors. In addition, Omics based approaches have gained increasing attention. In particular, redox proteomics can combine the assessment of oxidative stress with the advantage of getting more detailed mechanistic information. Here we propose a comprehensive testing strategy for assessing the oxidative stress potential of ENMs, which combines acellular methods and fast in vitro screening approaches, as well as a more involved detailed redox proteomics approach. This allows for screening and prioritization in a first tier and, if required, also for unraveling mechanistic details down to compromised signaling pathways.
authors.affiliation: German Federal Institute for Risk Assessment (BfR), Department of Chemicals and Product Safety, Berlin, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Riebeling
authors.affiliation: IBE R&D gGmbH, Institute for Lung Health, Münster, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Wiemann
authors.affiliation: Biomedical Technology Center, Westfälische Wilhelms-University, Münster, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Schnekenburger
authors.affiliation: Institute of Energy and Environmental Technology (IUTA) e.V., Air Quality & Sustainable Nanotechnology, Duisburg, Germany; Center for Nanointegration CENIDE, University of Duisburg-Essen, Duisburg, Germany.
authors.forename: Thomas A J
authors.initials: TA
authors.lastname: Kuhlbusch
authors.affiliation: BASF SE, Material Physics, Ludwigshafen, Germany.
authors.forename: Wendel
authors.initials: W
authors.lastname: Wohlleben
authors.affiliation: German Federal Institute for Risk Assessment (BfR), Department of Chemicals and Product Safety, Berlin, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Luch
authors.affiliation: German Federal Institute for Risk Assessment (BfR), Department of Chemicals and Product Safety, Berlin, Germany. Electronic address: andrea.haase@bfr.bund.de.
authors.forename: Andrea
authors.initials: A
authors.lastname: Haase
mesh_terms: D002616:Chemical Engineering / Q000379:methods; D049329:Nanostructures / Q000737:chemistry* / Q000633:toxicity*; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D040901:Proteomics / Q000379:methods*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species
keywords: Acellular tests; Oxidative stress; Protein carbonylation; Proteomics; Toxicity mechanisms