Investigating the Molecular Processes behind the Cell-Specific Toxicity Response to Titanium Dioxide Nanobelts
| Autor: | Chris T. Evelo, Laurent A. Winckers, Martina Kutmon, Egon Willighagen |
|---|---|
| Přispěvatelé: | Bioinformatica, RS: NUTRIM - R1 - Obesity, diabetes and cardiovascular health, RS: FHML MaCSBio, RS: FSE MaCSBio, RS: FPN MaCSBio, Maastricht Centre for Systems Biology |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Cell
Monocytes Gene expression NANOPARTICLES Cytotoxic T cell Biology (General) OXIDATIVE STRESS Cells Cultured Spectroscopy nanomaterials Titanium Chemistry THP1 General Medicine SAE Computer Science Applications APOPTOSIS overrepresentation analysis medicine.anatomical_structure nanobelts Colonic Neoplasms medicine.symptom HT29-MTX PACKAGE EXPRESSION QH301-705.5 DNA damage Inflammation Computational biology Adenocarcinoma CARBON NANOTUBES Article Catalysis Inorganic Chemistry ENGINEERED NANOMATERIALS medicine Humans EXPOSURE Physical and Theoretical Chemistry SPRAGUE-DAWLEY RATS QD1-999 Molecular Biology Gene titanium dioxide Gene Expression Profiling Organic Chemistry PATHWAYS Caco-2 Caco-2/HT29-MTX Gene Ontology Gene Expression Regulation Cell culture DNA Damage |
| Zdroj: | International Journal of Molecular Sciences Volume 22 Issue 17 International Journal of Molecular Sciences, 22(17):9432. Multidisciplinary Digital Publishing Institute (MDPI) International Journal of Molecular Sciences, Vol 22, Iss 9432, p 9432 (2021) |
| ISSN: | 1661-6596 |
| DOI: | 10.3390/ijms22179432 |
| Popis: | BackgroundWhereas several engineered nanomaterials are able to incite toxicological effects, the underlying molecular processes are understudied. And the varied physicochemical properties complicate toxicological predictions. Gene expression data allow us to study the cell-specific responses of individual genes, whereas their role in biological processes is harder to interpret. An overrepresentation analysis allows us to identify enriched biological processes and link the experimental data to these, but still prompt broad results which complicates the analysis of detailed toxicological processes. We demonstrated a targeted filtering approach to compare the cell-specific effects of two concentrations of the widely used nanomaterial titanium dioxide (TiO2) -nanobelts.MethodsWe compared public gene expression data generated by Tilton et al. from colon endothelium cells (Caco2), lung endothelium cells (SAE), and monocytic like cells (THP1) after 24-hour exposure to low (10 μg/ml) and high (100 μg/ml) concentrations of TiO2 -nanobelts. We used pathway enrichment analysis of the WikiPathways collection to identify cell and concentration-specific affected pathways. Gene sets from selected Gene Ontology terms (apoptosis, inflammation, DNA damage response and oxidative stress) highlighted pathways with a clear toxicity focus. Finally, pathway-gene networks were created to show the genetic overlap between the altered toxicity-related pathways.ResultsAll cell lines showed more differentially expressed genes after exposure to higher concentration, but our analysis found clear differences in affected molecular processes between the cell lines. Approximately half of the affected pathways are categorized with one of the selected toxicity-related processes. Caco2 cells show resilience to low and high concentrations. SAE cells display some cytotoxic response to the high concentration, while THP1 cells are already strongly affected at a low concentration. The networks show for up- and downregulation for the THP1 cells the most pathways. Additionally, the networks show gene overlap between almost all pathways for all conditions.ConclusionsThe approach allowed us to focus the analysis on affected cytotoxic processes and highlight cell-specific effects. The results showed that Caco2 cells are more resilient to TiO2 -nanobelts exposure compared to SAE cells, while THP1 cells were affected the most. The automated workflow can be easily adapted using other Gene Ontology terms focusing on other biological processes. |
| Databáze: | OpenAIRE |
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