作者： Zeng, Can;Feng, Yuqin;Wang, Wuxiang;Zhou, Furong;Liao, Fen;Liu, Yuanfeng;Feng, Shaolong

期刊： Environmental Toxicology,2018年33(12):1221-1228 ISSN：1522-7278

通讯作者： Feng, SL

作者机构： [Zeng, Can; Wang, Wuxiang; Zhou, Furong; Liao, Fen; Liu, Yuanfeng; Feng, Shaolong] Univ South China, Sch Publ Hlth, Hengyang 421001, Peoples R China.;[Feng, Yuqin] Jilin Univ, Coll Mat Sci & Engn, Changchun, Jilin, Peoples R China.;[Wang, Wuxiang] Univ South China, The Lib, Hengyang, Peoples R China.

通讯机构： [Feng, SL ] Univ South China, Sch Publ Hlth, Hengyang 421001, Peoples R China.;Univ South China, Sch Publ Hlth, Hengyang 421001, Peoples R China.

关键词： apoptosis<&wdkj&>endothelial cell (EC)<&wdkj&>p53<&wdkj&>titanium dioxide nanoparticle (nano‐TiO2)

摘要： Concerns over the health risk of the widely distributed, commonly used titanium dioxide nanoparticles (nano-TiO2) are increasing worldwide. Yet, up-to-now, our understanding in their potential effects on the cardiovascular system is very limited and the toxicological mechanisms are still unclear. In the present study, the CCK-8 assay was performed to determine the cytotoxicity of four sizes (10, 30, 50, and 100 nm) of anatase nano-TiO2 on human umbilical vein endothelial cells (HUVECs) in culture, and the flow cytometry was employed to investigate the potential of these nano-TiO2 to induce the apoptosis of HUVECs. The apoptotic pathway was also probed through the determination of the protein expression and activation of p53, Bax, Bcl-2, caspases-9, -7, -3, and PARP by western blot. The results showed that at the administrative levels (1, 5, 25 μg/mL), all the four sizes of nano-TiO2 could significantly inhibit the viability of HUVECs and elicit significant apoptosis in them, compared with the negative control (P <.05, P <.01). Moreover, the apoptotic rates of HUVECs were increased respectively with the elevating levels and decreasing sizes of the administrative nano-TiO2, showing a clear dose- and size-dependent effect relationships. Interestingly, the increasing phosphorylation of p53, decreasing ratio of Bcl-2/Bax, and enhancing activation of the downstream proteins caspase-9, -7, -3, and PARP, were also observed with the decreasing sizes of the administrative nano-TiO2 in the western blot, indicating that the intracellular approach of apoptosis, the p53-caspase pathway, is the major way of the nano-TiO2-mediated apoptosis in HUVECs in culture and that the size is an important parameter that may determine the potential of nano-TiO2 to induce cellular response. In conclusion, these results suggested that high levels of nano-TiO2 exposure may pose potential risks to human cardiovascular health by inducing cardiovascular EC apoptosis. © 2018 Wiley Periodicals, Inc.

语种： 英文