Toxic effect of silica nanoparticles on endothelial cells through DNA damage response via Chk1-dependent G2/M checkpoint.
Toxic effect of silica nanoparticles on endothelial cells through DNA damage response via Chk1-dependent G2/M checkpoint.
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DOI：
10.1371/journal.pone.0062087
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Sun Z
中科院分区：
文献类型：
--
作者：
Duan J;Yu Y;Li Y;Yu Y;Li Y;Zhou X;Huang P;Sun Z
二氧化硅纳米粒子已成为药物输送或基因治疗的有前途的载体。内皮细胞可以通过静脉内施用直接暴露于二氧化硅纳米颗粒。然而，二氧化硅纳米颗粒对内皮细胞的潜在毒性作用机制仍然知之甚少。为探讨二氧化硅纳米颗粒对内皮细胞的毒性作用及其机制，以人脐静脉内皮细胞（HUVECs）为研究对象，通过观察细胞形态、细胞活力和乳酸脱氢酶（LDH）释放来评价二氧化硅纳米颗粒对内皮细胞的毒性作用，结果显示二氧化硅纳米颗粒对内皮细胞的毒性作用具有剂量和时间依赖性。二氧化硅纳米颗粒诱导的活性氧（ROS）的产生引起氧化损伤，随后产生丙二醛（MDA）以及抑制超氧化物歧化酶（SOD）和谷胱甘肽过氧化物酶（GSH-Px）。染毒24 h后细胞坏死和凋亡均明显增加。线粒体膜电位（MMP）呈剂量依赖性下降。DNA损伤程度包括尾DNA百分率、尾长和Olive尾矩（OTM）均明显加重。SiO2纳米颗粒还通过上调Chk 1和下调Cdc 25 C、cyclin B1/Cdc 2诱导G2/M期阻滞。综上所述，二氧化硅纳米颗粒对内皮细胞的毒性作用机制是通过Chk 1依赖的G2/M检查点信号通路介导的DNA损伤反应（DDR），提示二氧化硅纳米颗粒暴露可能对心血管疾病的发生具有潜在危害。
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.
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影响因子：
17.1
作者：
Kumar R;Roy I;Ohulchanskky TY;Vathy LA;Bergey EJ;Sajjad M;Prasad PN
通讯作者：
Prasad PN
影响因子：
5.6
作者：
Kang, Jiunn-Horng;Keller, Joseph J.;Lin, Herng-Ching
通讯作者：
Lin, Herng-Ching
影响因子：
14
作者：
Liu, Xin;Sun, Jiao
通讯作者：
Sun, Jiao
影响因子：
16
作者：
Ciccia A;Elledge SJ
通讯作者：
Elledge SJ
影响因子：
3.2
作者：
Li, Yang;Sun, Lei;Sun, Zhiwei
通讯作者：
Sun, Zhiwei