論文 - 詳細
| RRC ID | 59345 |
|---|---|
| 著者 | Gallud A, Klöditz K, Ytterberg J, Östberg N, Katayama S, Skoog T, Gogvadze V, Chen YZ, Xue D, Moya S, Ruiz J, Astruc D, Zubarev R, Kere J, Fadeel B. |
| タイトル | Cationic gold nanoparticles elicit mitochondrial dysfunction: a multi-omics study. |
| ジャーナル | Sci Rep |
| Abstract |
Systems biology is increasingly being applied in nanosafety research for observing and predicting the biological perturbations inflicted by exposure to nanoparticles (NPs). In the present study, we used a combined transcriptomics and proteomics approach to assess the responses of human monocytic cells to Au-NPs of two different sizes with three different surface functional groups, i.e., alkyl ammonium bromide, alkyl sodium carboxylate, or poly(ethylene glycol) (PEG)-terminated Au-NPs. Cytotoxicity screening using THP-1 cells revealed a pronounced cytotoxicity for the ammonium-terminated Au-NPs, while no cell death was seen after exposure to the carboxylated or PEG-modified Au-NPs. Moreover, Au-NR3+ NPs, but not the Au-COOH NPs, were found to trigger dose-dependent lethality in vivo in the model organism, Caenorhabditis elegans. RNA sequencing combined with mass spectrometry-based proteomics predicted that the ammonium-modified Au-NPs elicited mitochondrial dysfunction. The latter results were validated by using an array of assays to monitor mitochondrial function. Au-NR3+ NPs were localized in mitochondria of THP-1 cells. Moreover, the cationic Au-NPs triggered autophagy in macrophage-like RFP-GFP-LC3 reporter cells, and cell death was aggravated upon inhibition of autophagy. Taken together, these studies have disclosed mitochondria-dependent effects of cationic Au-NPs resulting in the rapid demise of the cells. |
| 巻・号 | 9(1) |
| ページ | 4366 |
| 公開日 | 2019-3-13 |
| DOI | 10.1038/s41598-019-40579-6 |
| PII | 10.1038/s41598-019-40579-6 |
| PMID | 30867451 |
| PMC | PMC6416392 |
| MeSH | Ammonium Compounds / chemistry Autophagy / drug effects Cations / chemistry Cations / pharmacology* Cell Death / drug effects Cell Line, Tumor Chemical Phenomena Dose-Response Relationship, Drug Gene Expression Profiling Gold / chemistry Gold / pharmacology* Humans Metabolic Networks and Pathways Metal Nanoparticles* / chemistry Metal Nanoparticles* / ultrastructure Mitochondria / drug effects* Mitochondria / genetics Mitochondria / metabolism Mitochondria / ultrastructure Oxidative Phosphorylation Proteome Proteomics / methods Transcriptome |
| IF | 4.011 |
| 引用数 | 10 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 5 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.2 |
| リソース情報 | |
| 線虫 | tm690 |