Dataset Information

Short-term inhalation exposure to copper oxide nanoparticles induces gene expression changes associated with inflammation and cell proliferation in rat bronchoalveolar epithelium

ABSTRACT: Copper oxide nanoparticles (CuO NPs) are considered for various technological and consumer applications, leading to growing concerns for potential human hazards resulting from inhalation. Recent studies have revealed a dose-dependent toxicity of CuO NPs in rats following short-term inhalation exposure. Here, we utilized transcriptomics approaches to further investigate the responses in rats exposed via inhalation for five consecutive days to two doses of CuO NPs, 3.3 (low dose, LD) and 13.2 (high dose, HD) mg/m3, with collection of lung tissues on days 6 (1 day post-exposure) and 28 (i.e., after a 22-day post-exposure recovery period). Histopathology confirmed an acute inflammatory response that was resolved during the post-exposure phase. Global gene expression analyses yielded about 1,000 differentially expressed genes in HD rats and 200 in LD on day 6, and less than 20 after the recovery period. Pathway analysis indicated cell proliferation/survival and inflammation as the main processes triggered by exposure and identified epithelial cell transforming protein 2 (Ect2) as a potential gene of interest implicated in cell proliferation. Indeed, ECT2 was upregulated in exposed lungs and was localized in the cytoplasm of alveolar epithelial cells in HD rats, in hyperplasic foci identified based on the Ki67 antigen, a marker of cell proliferation. Monocyte chemoattractant protein 1 (MCP-1, also known as CCL2), with an important role in the regulation of inflammatory processes and cell proliferation, was also upregulated and this was confirmed immunohistochemically. Finally, we could not find any evidence for aberrant DNA methylation of inflammation-associated genes in response to CuO NP exposure. In summary, the current findings suggest that airborne CuO NPs cause an acute response that translates into inflammation and cellular proliferation in bronchoalveolar epithelium, with upregulation of neoplasia-related factors even after a short-term exposure.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE86390 | GEO | 2018/09/01

REPOSITORIES: GEO

ACCESS DATA

Shared Molecules

Only show the datasets with similarity scores above: 0.5

Threshold

0.5

Similar Datasets

Project description:Purpose: The intensive use of metal-based nanoparticles results in their continuous release into the environment and the subsequent destroying microbial biodiversity and causing occurrence of antibiotic resistant determinants. Although previous studies have indicated that nanoparticles may be toxic to microorganisms, there is a scarcity of data available to assess the underlying molecular mechanisms of inhibitory and biocidal effects of nanoparticles on microorganisms, which is a critical gap in our comprehensive understanding of the impacts of nanoparticles on microbial ecosystems. Methods: By combining the global activated/suppressed gene profiles and detected physiological responses, we detected the microbial response to CuO NPs exposure and revealed potential mechanisms of CuO NPs on this prevalent opportunistic pathogen and environmentally relevant denitrifier. Results:Our results indicate that nanoparticles could react directly with the biological membrane, but also change gene expressions. Transmission electron microscopy (TEM) results indicate that CuO nanoparticles not only damaged the structure of the bacterial membrane but also entered the cells. Planktonic cells of P. aeruginosa are energetically compromised after exposure to a sublethal level (1 and 10 mg/L) of CuO nanoparticles. Respiration was likely inhibited as denitrification activity was severely depleted in terms of decreased transcript levels of most denitrification genes. In addition, and of high concern, bacteriophage genes were activated and it is speculated that phage mediated cell lysis. Meanwhile, CuO NP exposure induced significantly up-regulated expressions of metal resistance gene, resistance-nodulation-division, P-type ATPase efflux and cation diffusion facilitator transporters, which can form an integrated network controlling metals concentrations in the cytoplasm and periplasm P. aeruginosa. Conclusion: Based on our results, it is evident that the response of bacteria under the exposure of nanoparticles is very complex, though a clear and comprehensive understanding of the true mechanisms of inhibition or toxicity is still lacking. Our findings will provide insights on whole picture regarding the fundamental mechanisms of microbial susceptibility, tolerance and resistance to exposure of CuO NPs, as well highlight to re-estimate potential risks of CuO NP to public health and environment.