| 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
|
| リソース情報 |
| 線虫 |
tm690 |
