Department of Ophthalmology, Weifang Medical University, Weifang 261042, Shandong Province, China.
Aging (Albany NY). 2021 Feb 1;13(4):5020-5033. doi: 10.18632/aging.202412.
Titanium dioxide nanoparticles (TiO NPs) are widely used in a variety of areas. However, TiO NPs possess cytotoxicity which involves oxidative stress. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a key molecule preventing cells from oxidative stress damage. In the current study, we explored the effect of Nrf2 signaling pathway in TiO NPs-induced corneal endothelial cell injury. Firstly, we found TiO NPs inhibited proliferation and damaged morphology and mitochondria of mouse primary corneal endothelial cells. Moreover, TiO NPs-induced oxidative damage of mouse primary corneal endothelial cells was inhibited by antioxidant NAC by evaluating production of reactive oxygen species (ROS), malondialdehyde (MDA), and activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). Next, flow cytometry analysis showed TiO NPs promoted apoptosis and cell cycle G2/M phase arrest of mouse primary corneal endothelial cells. Further investigation suggested that Nrf2 signaling pathway activation and the downregulation of ZO-1, β-catenin and Na-K-ATPase were involved in TiO NPs-induced mouse primary corneal endothelial cell injury. Our research highlighted the toxic effect of TiO NPs on corneas and , providing an alternative insight into TiO NPs-induced corneal endothelial cell injury.
二氧化钛纳米粒子(TiO NPs)广泛应用于多种领域。然而,TiO NPs 具有细胞毒性,涉及氧化应激。核因子红细胞 2 相关因子 2(Nrf2)是防止细胞氧化应激损伤的关键分子。在本研究中,我们探讨了 Nrf2 信号通路在 TiO NPs 诱导的角膜内皮细胞损伤中的作用。首先,我们发现 TiO NPs 抑制了小鼠原代角膜内皮细胞的增殖,并破坏了其形态和线粒体。此外,抗氧化剂 NAC 可通过评估活性氧(ROS)、丙二醛(MDA)、超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GSH-Px)的产生来抑制 TiO NPs 诱导的小鼠原代角膜内皮细胞氧化损伤。接下来,流式细胞术分析表明 TiO NPs 促进了小鼠原代角膜内皮细胞的凋亡和细胞周期 G2/M 期阻滞。进一步的研究表明,Nrf2 信号通路的激活以及 ZO-1、β-连环蛋白和 Na-K-ATP 酶的下调参与了 TiO NPs 诱导的小鼠原代角膜内皮细胞损伤。我们的研究强调了 TiO NPs 对角膜的毒性作用,并为 TiO NPs 诱导的角膜内皮细胞损伤提供了新的见解。