Proteome profiling reveals potential toxicity and detoxification pathways following exposure of BEAS‐2B cells to engineered nanoparticle titanium dioxide

Abstract

Oxidative stress is known to play important roles in engineered nanomaterial-induced cellular toxicity. However, the proteins and signaling pathways associated with the engineered nanomaterial-mediated oxidative stress and toxicity are largely unknown. To identify these toxicity pathways and networks that are associated with exposure to engineered nanomaterials, an integrated proteomic study was conducted using human bronchial epithelial cells, BEAS-2B and nanoscale titanium dioxide. Utilizing 2-DE and MS, we identified 46 proteins that were altered at protein expression levels. The protein changes detected by 2-DE/MS were verified by functional protein assays. These identified proteins include some key proteins involved in cellular stress response, metabolism, adhesion, cytoskeletal dynamics, cell growth, cell death, and cell signaling. The differentially expressed proteins were mapped using Ingenuity Pathway Analyses™ canonical pathways and Ingenuity Pathway Analyses tox lists to create protein-interacting networks and proteomic pathways. Twenty protein canonical pathways and tox lists were generated, and these pathways were compared to signaling pathways generated from genomic analyses of BEAS-2B cells treated with titanium dioxide. There was a significant overlap in the specific pathways and lists generated from the proteomic and the genomic data. In addition, we also analyzed the phosphorylation profiles of protein kinases in titanium dioxide-treated BEAS-2B cells for a better understanding of upstream signaling pathways in response to the titanium dioxide treatment and the induced oxidative stress. In summary, the present study provides the first protein-interacting network maps and novel insights into the biological responses and potential toxicity and detoxification pathways of titanium dioxide.

The bio-nano-interface in predicting nanoparticle fate and behaviour in living organisms: towards grouping and categorising nanomaterials and ensuring nanosafety by design

“…Utilizing 2-DE and MS, 46 proteins that were altered at protein expression levels were identified and mapped, using Ingenuity Pathway Analyses™ (IPA) canonical pathways and Ingenuity Pathway Analyses tox lists, to create protein-interacting networks and proteomic pathways. This provided the first preliminary protein-interacting network maps and may give novel insights into the biological responses and potential toxicity and detoxification pathways of titanium dioxide [111]. However, as with many early studies in an emerging field, there are some concerns regarding how much can be interpreted from this study which lacked appropriate controls [e.g., no bulk TiO 2 or other (reference) material has been used for comparison].…”

“…with exposure of human bronchial epithelial cells to nanoscale titanium dioxide [111]. Utilizing 2-DE and MS, 46 proteins that were altered at protein expression levels were identified and mapped, using Ingenuity Pathway Analyses™ (IPA) canonical pathways and Ingenuity Pathway Analyses tox lists, to create protein-interacting networks and proteomic pathways.…”

“…An important advance in understanding nanoparticle-induced signalling and toxicity has been achieved utilising an integrated proteomics approach, as routinely used to identify protein interaction pathways, to identify the toxicity pathways and networks that are associated [111]. Whether, in this particular case the impacts can be best described as "signalling" or "perturbation of signalling" pathways is open to debate, but the possibility that that signalling may take place at the bio-nano-interface and as such needs to be considered in the design, and interpretation, of nanosafety and nanointeraction studies is one the main messages of the present review.…”

Environmental OMICS: Current Status and Future Directions

“…Traditional environmental toxicology and environmental health research mainly focus on the effects of environmental chemicals on the functions of various organ systems or toxicity phenotypes and modes of actions of the chemicals at cellular levels, usually relying on animal models for these studies [5,21]. In addition to being labor-, time-and resource-intensive, this approach is primarily descriptive in nature and is low throughput and unable to characterize the full spectrum of targets and toxicity mechanisms for chemicals that affect multiple systems.…”

“…For example, genomic, proteomic, and metabolomic technologies have been used extensively to study the molecular mechanisms of how arsenic acts as a carcinogen [3,4]. Also, the difference in gel electrophoresis (DIGE) proteomics technology has been used to decipher toxicity pathways and detoxification pathways of nanomaterials, proteininteracting network maps, biological response, potential toxicity, and detoxification pathways in titanium dioxidetreated BEAS-2B cells [5]. Proteomics was also applied to the investigation of differential proteomes of environmental bacteria for a better understanding of antibiotic and antibiotic-resistance mechanisms [6].…”