期刊
TOXICOLOGICAL SCIENCES
卷 125, 期 2, 页码 462-472出版社
OXFORD UNIV PRESS
DOI: 10.1093/toxsci/kfr319
关键词
zinc oxide nanoparticles; zinc ion; cytosolic zinc ion concentration; mitochondrial zinc ion concentration; mitochondria membrane potential; caspase-3
类别
资金
- National Science Council
- National Science Council, Taiwan, Republic of China [NSC-96-2621-Z-031-001, NSC-97-2320-B-031-001]
The toxicological effects of zinc oxide nanoparticles (ZnO-NPs) are attracting increasing concern as the field of nanotechnology progresses. Although the literature suggests that toxicity of ZnO-NPs may be related to their dissolution, the mechanism for ZnO-NP perturbation of cytosolic zinc concentration ([Zn2+](c)) homeostasis remains obscure. Using FluoZin-3 and RhodZin-3, this study investigated changes in both [Zn2+](c) and mitochondrial free Zn2+ concentration ([Zn2+](m)) under conditions of ZnO-NP treatment in vivo and in vitro. In human leukemia Jurkat cells and human lung carcinoma H1355 cells, ZnO-NP treatment resulted in an elevation of both [Zn2+](c) and [Zn2+](m). In H1355 cells, ZnO-NP treatment induced depolarization of mitochondrial membrane potential, as well as caspase-3 activation and lactic dehydrogenase (LDH) release. In our in vivo experiments, when rats were exposed to ZnO-NPs, higher [Zn2+](c) and [Zn2+](m) were recorded in both broncho-alveolar lavage (BAL) cells and white blood cells isolated from ZnO-NP-exposed rats, compared with high efficiency particulate air-filter-protected controls LDH levels were also elevated in the BAL of ZnO-NP-exposed rats compared with controls. A mechanical toxicological pathway for ZnO-NP toxicity is suggested by these results: an elevation in [Zn2+](c) resulting from ZnO-NP dissolution in the intracellular endosome; cytosolic Zn2+ sequestration by mitochondria; and elevated [Zn2+](m) leading to mitochondrial dysfunction, caspase activation, and cell apoptosis. We conclude that exposure to ZnO-NPs interferes with the homeostasis of [Zn2+](c,) and that elevated [Zn2+](c) results in cell apoptosis.
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