School of Life Sciences, Yunnan Normal University, Kunming, Yunnan, 650500, China.
School of Life Sciences, Yunnan Normal University, Kunming, Yunnan, 650500, China; Engineering Research Center of Sustainable Development and Utilization of Biomass Energy, Ministry of Education, Kunming, Yunnan, 650500, China.
Biochem Biophys Res Commun. 2018 Sep 5;503(2):697-702. doi: 10.1016/j.bbrc.2018.06.063. Epub 2018 Jun 18.
Titanium dioxide nanoparticles (TiO-NPs) have raised serious attention for their widely use and potential adverse effects on human mainly due to producing ROS. However, the influence of TiO-NPs on telomere maintaining has not been studied clearly. Shelterin plays core roles in telomere length (TL) regulation. Abnormal TL are associated with chromosome instability (CIN) and high risk of diseases. This study investigated whether TiO-NPs affect TL to induce CIN through ROS generation and the possible mechanisms. Human hepatocyte L-02 and hepatocarcinoma cells QGY were exposed to TiO-NPs (0, 40, 80 μg/mL) for 72 h. The intracellular hydrogen dioxide (HO) concentration were measured. The TL, Nrf-2, and three core shelterin components (TRF1, TRF2, and POT1) transcription level were determined by quantitative real-time PCR. CIN was measured by cytokinesis-block micronucleus assay. TiO-NPs exposure increased intracellular HO in both L-02 and QGY cells, and induced Nrf-2, TRF1, TRF2, POT1 downregulated transcription compared with control (P < 0.001) in L-02 but all upregulated (P < 0.05) in QGY. Significant TL shortening (P < 0.001) and CIN increase (P < 0.01) in L-02 cells were observed but not in QGY cells. The differentially responses of the tested components of shelterin and Nrf-2 to oxidative stress induced by TiO-NPs led to the weakened telomere protection in normal cells and effective telomere maintenance in cancer cells, respectively. The upregulation of Nrf-2 and shelterin could protect TL and chromosome stability against TiO-NPs exposure.
二氧化钛纳米粒子（TiO-NPs）由于产生 ROS 而被广泛应用并可能对人体产生不良影响，引起了人们的高度关注。然而，TiO-NPs 对端粒维持的影响尚未得到明确研究。端粒结合蛋白（shelterin）在端粒长度（TL）调节中发挥核心作用。异常的 TL 与染色体不稳定（CIN）和疾病风险增加有关。本研究通过 ROS 生成探讨了 TiO-NPs 是否会影响 TL 以诱导 CIN，并探讨了可能的机制。人肝细胞 L-02 和肝癌细胞 QGY 分别暴露于 TiO-NPs（0、40、80μg/mL）72h。测量细胞内过氧化氢（HO）浓度。通过定量实时 PCR 测定 TL、Nrf-2 和三个核心端粒结合蛋白（TRF1、TRF2 和 POT1）的转录水平。通过胞质分裂阻断微核试验测量 CIN。TiO-NPs 暴露增加了 L-02 和 QGY 细胞内的 HO，并诱导 Nrf-2、TRF1、TRF2 和 POT1 的转录水平下调，与对照组相比（P<0.001），而在 QGY 中则全部上调（P<0.05）。在 L-02 细胞中观察到显著的 TL 缩短（P<0.001）和 CIN 增加（P<0.01），但在 QGY 细胞中没有观察到。氧化应激诱导的端粒结合蛋白和 Nrf-2 的测试成分的不同反应导致正常细胞的端粒保护减弱和癌细胞的有效端粒维持。Nrf-2 和 shelterin 的上调可以保护 TL 和染色体稳定性免受 TiO-NPs 暴露的影响。
