Abstract
Zinc oxide (ZnO) nanoparticle is added in various materials and products such as paints, plastics, ceramics, glass, rubber, pigments and sunscreen. Especially, ZnO nanoparticles are widely used in UV protection, because of their property of absorption ultraviolet light. Despite the widespread use of ZnO nanoparticles, there are many unknowns in understanding on their nanotoxicity and mechanisms.
In this study, we evaluated the effects of ZnO nanoparticles on gene expression pattern of human keratinocyte cells. Total RNA was prepared from the exposure groups to ZnO nanoparticles with different surface charge, and cDNA microarray was performed using Agilent human whole genome array. Our study indicated that genes related to apoptosis and response to stress including heme oxygenase 1 (HMOX1), superoxide dismutase (SOD), glutathione peroxidase (GPX), BNIP3L (adenovirus E1B 19 kDa interacting protein 3) and heat shock 70 kDa protein (HSP70) were upand down-regulated in ZnO nanoparticles treated cells. Moreover, our results showed that ZnO nanoparticles induced intracellular reactive oxygen species (ROS) and oxidative stress. Antioxidant enzyme SOD levels were significantly higher and GSH levels were decreased in ZnO nanoparticles-exposed cells, respectively.
The present study showed that up-regulation of these genes by ZnO nanoparticles could increase the production of ROS and oxidative stress. Therefore, ZnO nanoparticles could have a potential to product ROS through the perturbation of metabolic pathway, inducing oxidative stress. It also supported that the nanotoxicity mechanism could correlate with the active oxygen production, oxidative stress, apoptosis, and antioxidant defense mechanisms.
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References
Megan, J. et al. Zinc oxide nanoparticles in modern sunscreens: An analysis of potential exposure and hazard. Nanotoxicology 4:15–41 (2010).
Ilham, F. O. et al. Genotoxicity and cytotoxicity of zinc oxide and titanium dioxide in HEp-2 cells. Nanomedicine 5:1193–1203 (2010).
Fan, Z. & Lu, J. G. Zinc oxide nanostructures: synthesis and properties. J Nanosci Nanotechnol 5:1561–1573 (2005).
Yang, H., Liu, C., Yang, D., Zhang, H. & Xi, Z. Comparative study of cytotoxicity, oxidative stress and genotoxicity induced by four typical nanomaterials: the role of particle size, shape and composition. J Appl Toxicol 29:69–78 (2009).
Huang, Z. et al. Toxicological effect of ZnO nanoparticles based on bacteria. Langmuir 24:4140–4144 (2008).
Franklin, N. M. et al. Comparative toxicity of nanoparticulate ZnO, bulk ZnO, and ZnCl2 to a freshwater microalga (Pseudokirchneriella subcapitata): the importance of particle solubility. Environ Sci Technol 41:8484–8490 (2007).
Zhu, X. et al. Comparative toxicity of several metal oxide nanoparticle aqueous suspensions to Zebrafish (Danio rerio) early developmental stage. J Environ Sci Health A Toxicol 43:278–284 (2008).
Huang, C. C., Aronstam, R. S., Chen, D. R. & Huang, Y. W. Oxidative stress, calcium homeostasis, and altered gene expression in human lung epithelial cells exposed to ZnO nanoparticles. Toxicol in Vitro 24:45–55 (2010).
Xia, T. et al. Comparison of the mechanism of toxicity of zinc oxide and cerium oxide nanoparticles based on dissolution and oxidative stress properties. ACS Nano 2:2121–2134 (2008).
Jeng, H. A. & Swanson, J. Toxicity of metal oxide nanoparticles in mammalian cells. J Environ Sci Health A: Toxic Hazard Subst Environ Eng 41:2699–2711 (2006).
Lai, J. C. et al. Exposure to titaniumdioxide and othermetallic oxide nanoparticles induces cytotoxicity on human neural cells and fibroblasts. Int J Nanomed 3:533–545 (2008).
Horie, M. et al. Protein adsorption of ultrafine metal oxide and its influence on cytotoxicity toward cultured cells. Chem Res Toxicol 22:543–553 (2009).
Barbara, D. B. et al. Exposure to ZnO nanoparticles induces oxidative stress and cytotoxicity in human colon carcinoma cells. Toxicol and Appl Pharmacol 246:116–127 (2010).
Xiaoyong, D. et al. Nanosized zinc oxide particles induce neural stem cell apoptosis. Nanotechnology 20:111–118 (2009).
Maqusood, A. et al. ZnO nanorod-induced apoptosis in human alveolar adenocarcinoma cells via p53, survivin and bax/bcl-2 pathways: role of oxidative stress. Nanomedicine 7:904–913 (2011).
Gozzelino, R., Jeney, V. & Soares, M. P. Mechanisms of cell protection by heme oxygenase-1. Annu Rev Pharmacol Toxicol 50:323–354 (2010).
Briehl, M. M. & Baker, A. F. Modulation of the antioxidant defence as a factor in apoptosis. Cell Death Differ 3:63–70 (1996).
Neuschwander-Tetri, B. A. & Roll, F. J. Chemotactic activity for human PMN generated during ethanol metabolism by rat hepatocytes: role of glutathione and glutathione peroxidase. Biochem Biophys Res Commun 167:1170–1176 (1990).
Li, C. Y. et al. Heat shock protein 70 inhibits apoptosis downstream of cytochrome c release and upstream of caspase-3 activation. J Biol Chem 275:25665–25671 (2000).
Wan, J. et al. The Bcl-2 family pro-apoptotic molecule, BNIP3 regulates activation-induced cell death of effector cytotoxic T lymphocytes. Immunology 110:10–17 (2003).
Nel, A., Xia, T., Mädler, L. & Li, N. Toxic potential of materials at the nanolevel. Science 311:622–627 (2006).
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Lee, S.H., Pie, JE., Kim, YR. et al. Effects of zinc oxide nanoparticles on gene expression profile in human keratinocytes. Mol. Cell. Toxicol. 8, 113–118 (2012). https://doi.org/10.1007/s13273-012-0014-8
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DOI: https://doi.org/10.1007/s13273-012-0014-8