Toxic Effect of Silica Nanoparticles on Endothelial Cells through DNA Damage Response via Chk1-Dependent G2-M CheckpointReportar como inadecuado




Toxic Effect of Silica Nanoparticles on Endothelial Cells through DNA Damage Response via Chk1-Dependent G2-M Checkpoint - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Silica nanoparticles have become promising carriers for drug delivery or gene therapy. Endothelial cells could be directly exposed to silica nanoparticles by intravenous administration. However, the underlying toxic effect mechanisms of silica nanoparticles on endothelial cells are still poorly understood. In order to clarify the cytotoxicity of endothelial cells induced by silica nanoparticles and its mechanisms, cellular morphology, cell viability and lactate dehydrogenase LDH release were observed in human umbilical vein endothelial cells HUVECs as assessing cytotoxicity, resulted in a dose- and time- dependent manner. Silica nanoparticles-induced reactive oxygen species ROS generation caused oxidative damage followed by the production of malondialdehyde MDA as well as the inhibition of superoxide dismutase SOD and glutathione peroxidase GSH-Px. Both necrosis and apoptosis were increased significantly after 24 h exposure. The mitochondrial membrane potential MMP decreased obviously in a dose-dependent manner. The degree of DNA damage including the percentage of tail DNA, tail length and Olive tail moment OTM were markedly aggravated. Silica nanoparticles also induced G2-M arrest through the upregulation of Chk1 and the downregulation of Cdc25C, cyclin B1-Cdc2. In summary, our data indicated that the toxic effect mechanisms of silica nanoparticles on endothelial cells was through DNA damage response DDR via Chk1-dependent G2-M checkpoint signaling pathway, suggesting that exposure to silica nanoparticles could be a potential hazards for the development of cardiovascular diseases.



Autor: Junchao Duan, Yongbo Yu, Yang Li, Yang Yu, Yanbo Li, Xianqing Zhou, Peili Huang, Zhiwei Sun

Fuente: http://plos.srce.hr/



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