Genome-wide Transcriptional Analysis of Oxidative Stress-related Genes and Pathways Induced by CdTe aqQDs in Mice

Abstract

Objective: Quantum dots (QDs) has widely applied in the field of science, whose potential toxic effect has increasingly become a focus concern we need pay attention to in public health. The purpose of this article was to explore the toxicity mechanism with oxidative damage from treatment with QDs at the molecular level through a gene microarray.Methods: Mice were administered aqueously synthesized cadmium telluride QDs (CdTe aqQDs) via intravenous tail injection of a 2 µmol/kg solution (based on the molar mass of Cd), and their kidneys were collected at 1 day in strict accordance with the programs used for treated mice. We determined the hierarchical clustering of expression ratios, enriched gene ontology (GO) terms and signaling pathways through gene microarray analysis and bioinformatics analysis in kidney tissue and screened the key enzyme genes, which were verified by real-time quantitative polymerase chain reaction (real-time qPCR).Results: Compared to control group, 459 lncRNAs (197 down-regulated and 262 up-regulated) and 256 mRNAs (103 down-regulated and 153 up-regulated) were differentially expressed. According to biological processes in enriched GO terms, the response to a redox state played a significant role in the biological processes involved altered genes. Pathway analysis showed that the signaling pathways that involved cytochrome P450 (CYP450) enzymes had a close relationship with QDs. Among these signaling pathways, gene expression profiling revealed that selected differentially expressed mRNAs (CYP19A1, CYP1B1, CYP11A1, CYP11B2, and CYP17A1 in the kidney and CYP19A1 and CYP1B1 in the liver) were validated by real-time qPCR, resulting in expression levels of CYP11A1, CYP11B2 and CYP17A1 in the kidney and CYP19A1 and CYP1B1 in the liver that were significantly increased, however in expression levels of CYP19A1 and CYP1B1 compared with control group in the kidney, there was no significant difference.Conclusions: Our results provide a foundation for and potential insight into the role of CYP450-related genes in QD-induced oxidative stress. QDs may produce a great deal of reactive oxygen species (ROS) by promoting high expression of CYP450 enzymes and accumulating steroid hormones, which may be an important toxicity mechanism for mediating oxidative stress and tissue damage.

Gene Expression and Transcriptome Profiling of Changes in a Cancer Cell Line Post-Exposure to Cadmium Telluride Quantum Dots: Possible Implications in Oncogenesis

“…48 The RAS pathway is strongly modulated in HepG2 cells, 49 liver injury, and chronic liver diseases. 50,51 Furthermore, activation of integrin and focal adhesion kinase (FAK) signaling pathways, as observed here, suggests regulation of cell migration, cell proliferation, and angiogenesis, all of which are known to contribute to carcinogenesis in different cell types. [52][53][54] Genes involved in epithelial-mesenchymal transition (EMT) and G1/S checkpoint regulatory pathways were also noticeably upregulated, highlighting the potential for fibrosis, cancer progression 55 and oncogenesis.…”

Toxicogenomic Profiling of 28 Nanomaterials in Mouse Airways

“…The toxicity of CuO and Ag could arise from the release of toxic ions from the materials and/or oxidative stress through production of ROS. [ 18–21 ] However, free ion toxicity in the BAL seems unlikely as the maximum dissolution rates of the CuO material are <0.4% (3.67, 2.00, 1.81 and 3.71 µg min –1 from 800 µg of metal for CuO core , CuO NH2 , CUO COOH, and CuO PEG respectively, see Vassallo et al. 2018.…”

“…The toxicity of CuO and Ag could arise from the release of toxic ions from the materials and/or oxidative stress through production of ROS. [18][19][20][21] However, free ion toxicity in the BAL seems unlikely as the maximum dissolution rates of the CuO material are <0.4% (3.67, 2.00, 1.81 and 3.71 µg min -1 from 800 µg of metal for CuO core , CuO NH2 , CUO COOH, and CuO PEG respectively, see Vassallo et al 2018. Nonetheless, irritation of sensory nerves during Cu exposure is known to stimulate both adrenergic pathways and cortisol secretion, leading to a wider stress response and inflammation.…”

Does Nanosilver Exposure Modulate Steroid Metabolism in the Testes?—A Possible Role of Redox Balance Disruption

“…Furthermore, P450scc protein synthesis plays a crucial role in the synthesis of both pregnenolone and testosterone. Several authors reported that the Cyp11a1 gene may increase extra-gonadal tissues following oxidative stress induced by NPs [28]. In contrast to these findings, Dziendzikowska et al [3] demonstrated that a single intravenous administration of 20 nm AgNPs resulted in a significant decrease in Cyp11a1 and Hsd3b1 gene expressions and lowered testosterone and DHT levels in testes, compared to control animals 28 days after a single exposure.…”