College of Environmental Science and Engineering, South China University of Technology, The Key Laboratory of Pollution Control and Ecosystem Restoration in Industry Clusters (Ministry of Education), Guangzhou Higher Education Mega Center, Guangzhou 510006, China.
J Biomed Nanotechnol. 2012 Aug;8(4):669-75. doi: 10.1166/jbn.2012.1427.
Zinc oxide nanoparticles (ZnO NPs) are increasingly recognized for their cytotoxicity, whereas little is known about the toxicity mechanisms of ZnO NPs in human cells. To explore the possible molecular mechanisms for apoptosis induced by ZnO NPs, we investigated the relevant apoptotic signaling in human bronchial epithelial (16HBE) cells. ZnO NPs were found to induce intracellular reactive oxygen species (ROS) generation accompanied with the mitochondrial membrane potential (MMP, deltapsi(m)) reduction in 16HBE cells. Further, the expressions of two key apoptotic trigger regulators were determined by quantitative real time PCR and Western blot analysis. It demonstrated that following the exposure of 16HBE cells to ZnO NPs, both levels of mRNA and protein expression of c-Myc were significantly up-regulated, whereas the expressions of Bcl-2 mRNA and protein were down-regulated. Our results suggested that apoptosis induced by ZnO NPs might primarily involve the regulations of c-Myc and Bcl-2 gene expressions besides decline of MMP in 16HBE cells.
氧化锌纳米粒子（ZnO NPs）因其细胞毒性而日益受到关注，然而，关于 ZnO NPs 在人细胞中的毒性机制知之甚少。为了探讨 ZnO NPs 诱导细胞凋亡的可能分子机制，我们研究了人支气管上皮（16HBE）细胞中相关的凋亡信号。研究发现，ZnO NPs 可诱导人支气管上皮（16HBE）细胞内活性氧（ROS）的产生，并伴有线粒体膜电位（MMP，deltapsi(m)）的降低。进一步通过实时定量 PCR 和 Western blot 分析确定了两个关键的凋亡触发调节剂的表达。结果表明，16HBE 细胞暴露于 ZnO NPs 后，c-Myc 的 mRNA 和蛋白表达水平均显著上调，而 Bcl-2 mRNA 和蛋白的表达则下调。我们的结果表明，ZnO NPs 诱导的细胞凋亡可能主要涉及 c-Myc 和 Bcl-2 基因表达的调节，以及 MMP 的降低。
