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Molecular responses of human lung epithelial cells to the toxicity of copper oxide nanoparticles inferred from whole genome expression analysis.

ABSTRACT: This study proposes a molecular mechanism for lung epithelial A549 cell response to copper oxide nanoparticles (CuO-NPs) related to Cu ions released from CuO-NPs. Cells that survived exposure to CuO-NPs arrested the cell cycle as a result of the downregulation of proliferating cell nuclear antigen (PCNA), cell division control 2 (CDC2), cyclin B1 (CCNB1), target protein for Xklp2 (TPX2), and aurora kinase A (AURKA) and B (AURKB). Furthermore, cell death was avoided through the induced expression of nuclear receptors NR4A1 and NR4A3 and growth arrest and DNA damage-inducible 45 β and γ (GADD45B and GADD45G, respectively). The downregulation of CDC2, CCNB1, TPX2, AURKA, and AURKB, the expressions of which are involved in cell cycle arrest, was attributed to Cu ions released from CuO-NPs into medium. NR4A1 and NR4A3 expression was also induced by Cu ions released into the medium. The expression of GADD45B and GADD45G activated the p38 pathway that was involved in escape from cell death. The upregulation of GADD45B and GADD45G was not observed with Cu ions released into medium but was observed in cells exposed to CuO-NPs. However, because the expression of the genes was also induced by Cu ion concentrations higher than that released from CuO-NPs into the medium, the expression appeared to be triggered by Cu ions released from CuO-NPs taken up into cells. We infer that, for cells exposed to CuO-NPs, those able to make such a molecular response survived and those unable to do so eventually died.

ORGANISM(S): Homo sapiens

PROVIDER: GSE33278 | GEO | 2012/01/05

SECONDARY ACCESSION(S): PRJNA149077

REPOSITORIES: GEO

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Molecular responses of human lung epithelial cells to the toxicity of copper oxide nanoparticles inferred from whole genome expression analysis.

Project description:This study proposes a molecular mechanism for lung epithelial A549 cell response to copper oxide nanoparticles (CuO-NPs) related to Cu ions released from CuO-NPs. Cells that survived exposure to CuO-NPs arrested the cell cycle as a result of the downregulation of proliferating cell nuclear antigen (PCNA), cell division control 2 (CDC2), cyclin B1 (CCNB1), target protein for Xklp2 (TPX2), and aurora kinase A (AURKA) and B (AURKB). Furthermore, cell death was avoided through the induced expression of nuclear receptors NR4A1 and NR4A3 and growth arrest and DNA damage-inducible 45 Î² and Î³ (GADD45B and GADD45G, respectively). The downregulation of CDC2, CCNB1, TPX2, AURKA, and AURKB, the expressions of which are involved in cell cycle arrest, was attributed to Cu ions released from CuO-NPs into medium. NR4A1 and NR4A3 expression was also induced by Cu ions released into the medium. The expression of GADD45B and GADD45G activated the p38 pathway that was involved in escape from cell death. The upregulation of GADD45B and GADD45G was not observed with Cu ions released into medium but was observed in cells exposed to CuO-NPs. However, because the expression of the genes was also induced by Cu ion concentrations higher than that released from CuO-NPs into the medium, the expression appeared to be triggered by Cu ions released from CuO-NPs taken up into cells. We infer that, for cells exposed to CuO-NPs, those able to make such a molecular response survived and those unable to do so eventually died. Two-condition experiment, CuO-NPs exposured vs. non-treated cells. Hybridization: 2 replicates. Scanning: 3 replicates (Gain changed).

2012-01-05 | E-GEOD-33278 | biostudies-arrayexpress

Impact of copper oxide particle dissolution on lung epithelial cell toxicity: response characterization using global transcriptional analysis

Project description:The in vitro and in vivo toxicity of copper oxide nanoparticles (CuO NPs) is attributed to both particle and dissolved copper ion species. However, a clear understanding of 1) the specific cellular responses that are modulated by the two species and 2) the temporal dynamics in toxicity, as the proportional amount of particulate and ionic forms change over time, is lacking. In the current study, in vitro responses to microparticulate CuO (CuO MPs), CuO NPs, and dissolved Cu2+ were characterized in order to elucidate particle and ion induced kinetic effects. Particle dissolution experiments were carried out in relevant cell culture medium, using CuO NPs and MPs. Mouse lung epithelial cells were exposed for 2 - 48 h with 1 - 25 µg/mL CuO MPs, CuO NPs, or 7 & 54 µg/mL CuCl2. Cellular viability and genome-wide transcriptional responses were assessed. Dose and time dependent cytotoxicity was observed in CuO NP exposed cells, which was delayed and subtle in CuCl2 and not observed in CuO MPs treated cells. Analyses of differentially expressed genes and associated pathway perturbations showed that dissolved ions released by CuO NPs in extracellular medium are insufficient to account for the observed potency and cytotoxicity. Further organization of gene expression results in an Adverse Outcome Pathway (AOP) framework revealed a series of key events potentially involved in CuO NPs toxicity. The AOP is applicable to soluble metal oxide nanoparticle induced toxicity in general, and thus, can facilitate the development of in vitro alternative strategies to screen their toxicity.

2022-11-03 | GSE161017 | GEO

The effect of CuO nanoparticles on gene expression patterns in Daphnia magna

Project description:There is still a lot of contradiction on whether metal ions are solely responsible for the observed the toxicity of ZnO and CuO nanoparticles to aquatic species. While most tests have studied nanoparticle effects at organismal levels (e.g. mortality, reproduction), effects at suborganismal levels may clarify the role of metal ions, nanoparticles and nanoparticle aggregates. In this study, the effect of ZnO, CuO nanoparticles and zinc, copper salts was tested on the gene expression levels in Daphnia magna. D. magna was exposed during 96 hours to 10% immobilization concentrations of all chemicals, after which daphnids were sampled for a differential gene expression analysis using microarray. When comparing the nanoparticle exposed daphnids (ZnO or CuO) to the metal salt exposed daphnids (zinc or copper salt), the microarray results showed no significantly differentially expressed genes. These results indicate that the toxicity of the tested ZnO and CuO nanoparticles to D. magna caused is solely caused by toxic metal ions. 4 replicate exposures of ZnO nanoparticles, ZnCl2, Blank (for Zn); 4 replicate exposures of CuO nanoparticles, CuCl2.2H2O, Blank (for Cu); Individual reference design with swapped dyes for zinc (e.g. ZnO-REFZn; REFZn-bl) and copper exposure (e.g. CuO-REFCu; REFCu-bl); Zinc reference sample is a mixture of equal aliquots of ZnO nanoparticle, ZnCl2 and blank; Copper reference sample is a mixture of equal aliquots of CuO nanoparticle, CuCl2.2H2O and blank

2014-03-01 | E-GEOD-54738 | biostudies-arrayexpress

The effect of ZnO nanoparticles on gene expression patterns in Daphnia magna

2014-03-01 | E-GEOD-54736 | biostudies-arrayexpress

The Proteome of Enchytraeus crypticus – Exposure to CuO Nanomaterial and CuCl2

Project description:The transcriptome of the ecotoxicological model Enchytraeus crypticus is well studied but the downstream changes at the protein level remained a gap. Changes in the protein regulation following exposure to CuO nanomaterial (NM) and Cu salt (CuCl2) were investigated. High performance liquid chromatography with tandem mass spectrometry using tandem mass tags was used. CuO NM elicited higher number of differentially expressed proteins compared to CuCl2 with little to no overlap of proteins. CuO NM caused more stress response mechanisms, with good agreement between differentially expressed proteins, genes and metabolites. CuCl2 caused higher impact in shorter time periods, but organisms have conserved mechanisms (constitutive genes) that allow Cu handling and detoxification. CuO NM caused higher impact after a longer exposure period, inducing regulation of facultative genes with a whole differentiated paradigm and cascade. This could be due to different issues: 1) the cell uptake route is different for Cu NM and Cu ions 2) internalized Cu NM can result in a “Trojan- horse” effect 3) the cascade of events occurs in a different time order 4) the organism uptake is different between life stages, i.e., cocoons thickened surface protects the entry of NM and juveniles have facilitated entry via tegument. Protein responses are of key importance when trying to understand the link between exposure and the related adverse biological effects. We here used advanced proteomic profiling techniques to describe how the protein responses differ when an organism is exposed to Copper (Cu) nanomaterial compared to when it is exposure to Cu ions. We observed that when organisms are exposed to the nano-form they have longer-term changes in protein patterns, patterns that are different from the responses following exposure to the ionic form. On the level of individual proteins we identified nano-specific mechanisms.

2018-08-16 | PXD010647 | Pride

Genome-wide RNA sequencing of D. vulgaris respond to CuO nanoparticles exposure

Project description:Purpose: The objective of this study is to reveal the potential effects of CuO nanoparicles (NPs) on Desulfovibrio vulgaris Hildenborough (D. vulgaris) via genome-wide RNA sequencing Methods: RNA was harvested from D. vulgaris cultures in the presence and absence of CuO NPs (0, 1, 50, 250 mg CuO NPs/L) 8 h after cultivation.

2019-08-01 | GSE101911 | GEO

Next Generation Sequencing Facilitates Quantitative Analysis of Acinetobacter baylyi ADP1 Transcriptomes under heavy metal-based NPs and ions exposure

Project description:The goals of this study are to use Next-generation sequencing (NGS)to detect bacterial mRNA profiles of Acinetobacter baylyi ADP1 in response to 0, 1 mg/L AgNPs or Ag ions, 1 mg/L CuO NPs or Cu ions, 10 mg/L ZnO NPs or Zn ions for 2 h, in triplicate, using Illumina HiSeq 2500.The NGS QC toolkit (version 2.3.3) was used to treat the raw sequence reads to trim the 3’-end residual adaptors and primers, and the ambiguous characters in the reads were removed. Then, the sequence reads consisting of at least 85% bases were progressively trimmed at the 3’-ends until a quality value ≥ 20 were kept. Downstream analyses were performed using the generated clean reads of no shorter than 75 bp. The clean reads of each sample were aligned to the E. coli reference genome (NC_000913) using SeqAlto (version 0.5). Cufflinks (version 2.2.1) was used to calculate the strand-specific coverage for each gene, and to analyze the differential expression in triplicate bacterial cell cultures. The statistical analyses and visualization were conducted using CummeRbund package in R (http://compbio.mit.edu/cummeRbund/). Gene expression was calculated as fragments per kilobase of a gene per million mapped reads (FPKM, a normalized value generated from the frequency of detection and the length of a given gene.

2020-10-23 | GSE139295 | GEO

Copper oxide nanomaterial regulation and fate in Cucurbita pepo

Project description:Nanomaterials (NMs) are on the nanoscale level range ca. 1-100 nm and due to the peculiar physico-chemical properties are widely used in different areas. The present study aimed to characterize the responses of zucchini (Cucurbita pepo L.) treated with copper oxide (CuO) NPs from seed germination to the flowering stage. CuO NPs treatment did not negatively impact plant morphology and growth as well as the pollen formation and viability. Physiological analyses were followed by a complete RNAseq-based transcriptomic analysis in the different plant tissues. Mitochondrial and chloroplast functions emerged as a critical component in plant response. Evidence of CuO NPs internalization and biotransformation was a driving force to measure the impacts at both physiological and molecular levels.

2021-07-25 | GSE173716 | GEO

Project description:This study investigated the pulmonary toxicity of Copper oxide nanoparticles (CuO NPs) surface modified with polyethylenimine (PEI) or ascorbate (ASC), was investigated. Rats were exposed nose-only to a fixed exposure concentration of ASC or PEI coated CuO NPs for 5 consecutive days. On day 6 and day 27 post-exposure, pulmonary toxicity markers in bronchoalveolar lavage fluid (BALF) were analyzed and histopathological evaluation of the lungs was performed, along with microarray analyses on whole lung tissue samples.

2020-10-02 | GSE158900 | GEO

The effect of CuO nanoparticles on gene expression patterns in Daphnia magna

2014-03-01 | GSE54738 | GEO

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