Effects of Subtoxic Concentrations of Atrazine, Cypermethrin, and Vinclozolin on microRNA-Mediated PI3K/Akt/mTOR Signaling in SH-SY5Y Cells
Abstract
:1. Introduction
2. Results
2.1. ATZ, CYP and VNZ at Subtoxic Concentrations Have No Significant Cytotoxicity to SH-SY5Y Cells
2.2. ATZ, CYP and VNZ at Subtoxic Concentrations Have No Significant Effects on Reactive Oxygen Species Formation
2.3. Exposure to ATZ, CYP and VNZ at Subtoxic Concentrations Induce Alterations of miRNAs Profile
2.4. In Silico Prediction of miR-29b-3p Target Genes
2.5. Subtoxic Concentrations of VNZ Downregulate miR-29b-3p Contributing to the Increased Level of ADAM12 and CDK6 Genes in Differentiated SH-SY5Y Cells
2.6. Subtoxic Concentrations of VNZ Downregulate miR-29b-3p Contributing to the Activation of PI3K/Akt/mTOR Pathway and Suppress p53 Activation in Differentiated SH-SY5Y Cells
3. Discussion
4. Materials and Methods
4.1. Chemicals
4.2. Cell Culture
4.2.1. SH-SY5Y
4.2.2. SH-SY5Y Differentiation
4.3. EDCs Treatment
4.4. Determination of Neuronal Viability
4.5. Determination of ROS Formation Induced by EDCs
4.6. RNA Extraction
4.7. Quantitative Real-Time PCR (qRT-PCR) Analysis of miRNA Expression
4.8. Gene Expression Analysis by RNA Reverse Transcription and qRT-PCR
4.9. Western Blotting
4.10. In Silico Target Analysis
4.11. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Undifferentiated Cells | ||||||
---|---|---|---|---|---|---|
Target Name | ATZ 100 nM | ATZ 1 µM | CYP 100 nM | CYP 1 µM | VNZ 100 nM | VNZ 1 µM |
miR-18b-5p | 1.88 | 1.26 | 1.28 | 1.13 | 1.70 | 1.74 |
miR-29b-3p | 1.21 | 0.63 | 1.53 | 0.95 | 1.49 | 0.78 |
miR-146b-5p | 1.28 | 1.22 | 1.47 | 1.18 | 1.99 | 0.93 |
miR-452-5p | 1.94 | 1.24 | 1.41 | 1.45 | 1.46 | 1.90 |
miR-653-5p | 1.12 | 0.80 | 1.17 | 1.16 | 0.95 | 0.91 |
Differentiated cells | ||||||
Target name | ATZ 100 nM | ATZ 1 µM | CYP 100 nM | CYP 1 µM | VNZ 100 nM | VNZ 1 µM |
miR-18b-5p | 0.30 * | 0.65 | 0.95 | 0.67 | 0.26 * | 0.32 * |
miR-29b-3p | 0.42 * | 0.92 | 0.65 | 0.87 | 0.38 * | 0.70 |
miR-146b-5p | 0.49 * | 0.56 | 1.06 | 1.32 | 1.51 | 0.97 |
miR-452-5p | 0.55 | 1.09 | 0.81 | 0.86 | 0.57 | 0.25 * |
miR-653-5p | 0.41 * | 0.59 | 1.15 | 1.07 | 0.26 * | 0.32 * |
ADAM12 | Bcl2 | CDK6 | HDAC4 | |
---|---|---|---|---|
ATZ 100 nM | 1.20 | 1.31 | 1.28 | 1.12 |
CYP 100 nM | 1.43 | 1.56 | 1.98 | 1.30 |
VNZ 100 nM | 2.11 * | 1.99 | 2.13 * | 1.46 |
ATZ 1 µM | 1.38 | 1.13 | 1.58 | 1.32 |
CYP 1 µM | 1.34 | 1.05 | 1.74 | 1.46 |
VNZ 1 µM | 2.58 * | 1.60 | 2.97 * | 1.94 |
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Graziosi, A.; Sita, G.; Corrieri, C.; Angelini, S.; d’Emmanuele di Villa Bianca, R.; Mitidieri, E.; Sorrentino, R.; Hrelia, P.; Morroni, F. Effects of Subtoxic Concentrations of Atrazine, Cypermethrin, and Vinclozolin on microRNA-Mediated PI3K/Akt/mTOR Signaling in SH-SY5Y Cells. Int. J. Mol. Sci. 2022, 23, 14538. https://doi.org/10.3390/ijms232314538
Graziosi A, Sita G, Corrieri C, Angelini S, d’Emmanuele di Villa Bianca R, Mitidieri E, Sorrentino R, Hrelia P, Morroni F. Effects of Subtoxic Concentrations of Atrazine, Cypermethrin, and Vinclozolin on microRNA-Mediated PI3K/Akt/mTOR Signaling in SH-SY5Y Cells. International Journal of Molecular Sciences. 2022; 23(23):14538. https://doi.org/10.3390/ijms232314538
Chicago/Turabian StyleGraziosi, Agnese, Giulia Sita, Camilla Corrieri, Sabrina Angelini, Roberta d’Emmanuele di Villa Bianca, Emma Mitidieri, Raffaella Sorrentino, Patrizia Hrelia, and Fabiana Morroni. 2022. "Effects of Subtoxic Concentrations of Atrazine, Cypermethrin, and Vinclozolin on microRNA-Mediated PI3K/Akt/mTOR Signaling in SH-SY5Y Cells" International Journal of Molecular Sciences 23, no. 23: 14538. https://doi.org/10.3390/ijms232314538