The size‐dependent apoptotic effect of titanium dioxide nanoparticles on endothelial cells by the intracellular pathway. Issue 12 (20th August 2018)

• Record Type: Journal Article
• Authors: Zeng, Can; Feng, Yuqin; Wang, Wuxiang; Zhou, Furong; Liao, Fen; Liu, Yuanfeng; Feng, Shaolong
• Is Part Of: Environmental toxicology. Volume 33:Issue 12(2018)
• Page Start: 1221
• Page End: 1228
• Publication Date: 2018-08-20
• Subjects: apoptosis -- endothelial cell (EC) -- p53 -- titanium dioxide nanoparticle (nano‐TiO2); Water quality bioassay -- Periodicals; Water -- Pollution -- Toxicology -- Periodicals; Microbiological assay -- Periodicals; Toxicity testing -- Periodicals; Environmental toxicology -- Periodicals; Environmental Pollution -- Periodicals; Environmental Pollutants -- Periodicals; Environmental Monitoring -- Periodicals; Écotoxicologie -- Périodiques; Pollution -- Périodiques; 615.902
• DOI: 10.1002/tox.22628
• Languages: English
• ISSNs: 1520-4081

Abstract

Abstract: 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.