Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Therapy of Ocular Diseases of Shandong, Jinan 250002, China.
Int J Biochem Cell Biol. 2013 Aug;45(8):1849-59. doi: 10.1016/j.biocel.2013.06.002. Epub 2013 Jun 10.
Zinc oxide nanoparticle is one of the most important materials with diverse applications. However, it has been reported that zinc oxide nanoparticles are toxic to organisms, and that oxidative stress is often hypothesized to be an important factor in cytotoxicity mediated by zinc oxide nanoparticles. Nevertheless, the mechanism of toxicity of zinc oxide nanoparticles has not been completely understood. In this study, we investigated the cytotoxic effect of zinc oxide nanoparticles and the possible molecular mechanism involved in calcium homeostasis mediated by plasma membrane calcium ATPase in rat retinal ganglion cells. Real-time cell electronic sensing assay showed that zinc oxide nanoparticles could exert cytotoxic effect on rat retinal ganglion cells in a concentration-dependent manner; flow cytometric analysis indicated that zinc oxide nanoparticles could lead to cell damage by inducing the overproduction of reactive oxygen species. Furthermore, zinc oxide nanoparticles could also apparently decrease the expression level and their activity of plasma membrane calcium ATPase, which finally disrupt the intracellular calcium homeostasis and result in cell death. Taken together, zinc oxide nanoparticles could apparently decrease the plasma membrane calcium ATPase expression, inhibit their activity, cause the elevated intracellular calcium ion level and disrupt the intracellular calcium homeostasis. Further, the disrupted calcium homeostasis will trigger mitochondrial dysfunction, generate excessive reactive oxygen species, and finally initiate cell death. Thus, the disrupted calcium homeostasis is involved in the zinc oxide nanoparticle-induced rat retinal ganglion cell death.
氧化锌纳米粒子是一种非常重要的材料，具有多种应用。然而，据报道，氧化锌纳米粒子对生物体有毒，氧化应激通常被假设为氧化锌纳米粒子介导的细胞毒性的一个重要因素。然而，氧化锌纳米粒子的毒性机制尚未完全阐明。在这项研究中，我们研究了氧化锌纳米粒子的细胞毒性作用，以及在大鼠视网膜神经节细胞中由质膜钙 ATP 酶介导的钙稳态中涉及的可能分子机制。实时细胞电子感应分析显示，氧化锌纳米粒子可以以浓度依赖的方式对大鼠视网膜神经节细胞产生细胞毒性作用；流式细胞术分析表明，氧化锌纳米粒子可以通过诱导活性氧的过度产生导致细胞损伤。此外，氧化锌纳米粒子还可以明显降低质膜钙 ATP 酶的表达水平及其活性，最终破坏细胞内钙稳态并导致细胞死亡。总之，氧化锌纳米粒子可以明显降低质膜钙 ATP 酶的表达，抑制其活性，导致细胞内钙离子水平升高，破坏细胞内钙稳态。此外，钙稳态的破坏会引发线粒体功能障碍，产生过多的活性氧，最终引发细胞死亡。因此，钙稳态的破坏参与了氧化锌纳米粒子诱导的大鼠视网膜神经节细胞死亡。
