Zhang Ting, Hu Yuanyuan, Tang Meng, Kong Lu, Ying Jiali, Wu Tianshu, Xue Yuying, Pu Yuepu
Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, China.
Jiangsu Key Laboratory for Biomaterials and Devices, Southeast University, Nanjing 210009, China.
Int J Mol Sci. 2015 Sep 25;16(10):23279-99. doi: 10.3390/ijms161023279.
With the applications of quantum dots (QDs) expanding, many studies have described the potential adverse effects of QDs, yet little attention has been paid to potential toxicity of QDs in the liver. The aim of this study was to investigate the effects of cadmium telluride (CdTe) QDs in mice and murine hepatoma cells alpha mouse liver 12 (AML 12). CdTe QDs administration significantly increased the level of lipid peroxides marker malondialdehyde (MDA) in the livers of treated mice. Furthermore, CdTe QDs caused cytotoxicity in AML 12 cells in a dose- and time-dependent manner, which was likely mediated through the generation of reactive oxygen species (ROS) and the induction of apoptosis. An increase in ROS generation with a concomitant increase in the gene expression of the tumor suppressor gene p53, the pro-apoptotic gene Bcl-2 and a decrease in the anti-apoptosis gene Bax, suggested that a mitochondria mediated pathway was involved in CdTe QDs' induced apoptosis. Finally, we showed that NF-E2-related factor 2 (Nrf2) deficiency blocked induced oxidative stress to protect cells from injury induced by CdTe QDs. These findings provide insights into the regulatory mechanisms involved in the activation of Nrf2 signaling that confers protection against CdTe QDs-induced apoptosis in hepatocytes.
随着量子点(QDs)应用范围的不断扩大,许多研究都描述了量子点的潜在不良影响,但量子点在肝脏中的潜在毒性却很少受到关注。本研究的目的是调查碲化镉(CdTe)量子点对小鼠和小鼠肝癌细胞α小鼠肝脏12(AML 12)的影响。给予CdTe量子点显著增加了受试小鼠肝脏中脂质过氧化标志物丙二醛(MDA)的水平。此外,CdTe量子点以剂量和时间依赖性方式对AML 12细胞产生细胞毒性,这可能是通过活性氧(ROS)的产生和凋亡的诱导介导的。ROS生成增加,同时肿瘤抑制基因p53、促凋亡基因Bcl-2的基因表达增加,抗凋亡基因Bax减少,表明线粒体介导的途径参与了CdTe量子点诱导的凋亡。最后,我们表明NF-E2相关因子2(Nrf2)缺乏可阻断诱导的氧化应激,从而保护细胞免受CdTe量子点诱导的损伤。这些发现为Nrf2信号激活所涉及的调节机制提供了见解,该机制赋予了对CdTe量子点诱导的肝细胞凋亡的保护作用。