A proteome-wide assessment of the oxidative stress paradigm for metal and metal-oxide nanomaterials in human macrophages
- Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
Responsible implementation of engineered nanomaterials (ENMs) into commercial applications is an important societal issue, driving demand for new approaches for rapid and comprehensive evaluation of their bioactivity and safety. An essential part of any research focused on identifying potential hazard of ENMs is the appropriate selection of biological endpoints to evaluate. Herein, we use a tiered strategy employing both targeted biological assays and untargeted quantitative proteomics to elucidate the biological responses of human macrophages across a library of metal/metal oxide ENMs, raised as priority ENMs for investigation by NIEHS’s Nanomaterial Health Implications Research (NHIR) program. Our results show that quantitative cellular proteome profiles readily distinguish ENM types based on their cytotoxic potential according to induction of biological processes and pathways involved in the cellular antioxidant response, TCA cycle, oxidative stress, endoplasmic reticulum stress, and immune responses as major processes impacted. Interestingly, pathway analysis of differentially abundant proteins also revealed new cell processes that were influenced by all ENMs independent of cytotoxic potential. These included pathways previously implicated as cellular adaptive mechanisms to low levels of oxidative stress, including cell adhesion, protein translation and protein targeting pathways. Unsupervised clustering of all data revealed the most striking proteome changes that differentiated ENM classes involved a small subset of proteins involved in the oxidative stess response (HMOX1), protein chaperone functions (HS71B, DNJB1), and autophagy (SQSTM), providing a potential new panel of markers of ENM-induced cell stress. To our knowledge, the results represent the most comprehensive profiling of the biological responses to a library of ENMs conducted using quantitative mass spectrometry-based proteomics. The results provide a basis to identify the patterns of a diverse set of cellular pathways and cell processes impacted by ENM exposure in an important immune cell type, laying the foundation for multivariate, pathway-level structure activity assessments of ENMs in the future.
- Research Organization:
- Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)
- Sponsoring Organization:
- Nanotechnology Health Implications Research (NHIR) Consortium; National Institutes of Health (NIH); USDOE
- Grant/Contract Number:
- AC05-76RL01830
- OSTI ID:
- 1642069
- Report Number(s):
- PNNL-SA--147217
- Journal Information:
- NanoImpact, Journal Name: NanoImpact Vol. 17; ISSN 2452-0748
- Publisher:
- ElsevierCopyright Statement
- Country of Publication:
- United States
- Language:
- English
Similar Records
Mass spectrometry-based proteomics for system-level characterization of biological responses to engineered nanomaterials
Assessment of the Biological Impact of Engineered Nanomaterials Using Mass Spectrometry-based MultiOmics Approaches
A redox proteomics approach to investigate the mode of action of nanomaterials
Journal Article
·
Thu Jun 07 20:00:00 EDT 2018
· Analytical and Bioanalytical Chemistry
·
OSTI ID:1457755
Assessment of the Biological Impact of Engineered Nanomaterials Using Mass Spectrometry-based MultiOmics Approaches
Book
·
Mon May 15 00:00:00 EDT 2023
·
OSTI ID:1985980
A redox proteomics approach to investigate the mode of action of nanomaterials
Journal Article
·
Sun May 15 00:00:00 EDT 2016
· Toxicology and Applied Pharmacology
·
OSTI ID:22687943