Endothelial cells dysfunction induced by silica nanoparticles through oxidative stress via JNK/P53 and NF-κB pathways
Endothelial cells dysfunction induced by silica nanoparticles through oxidative stress via JNK/P53 and NF-κB pathways
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DOI：
10.1016/j.biomaterials.2010.07.069
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发表时间：
2010-11-01
期刊：
影响因子：
14
通讯作者：
Sun, Jiao
中科院分区：
文献类型：
--
作者：
Liu, Xin;Sun, Jiao
药物载体通常通过静脉内引入体内并直接暴露于内皮细胞。二氧化硅纳米粒子可能是有前途的药物靶向或基因治疗的载体。然而，很少有研究已经进行，以确定二氧化硅纳米粒子对内皮细胞的生物学行为。在这里，我们测量了活性氧（ROS）的产生，细胞凋亡和坏死，促炎和促血栓形成的特性和水平的凋亡信号蛋白和转录因子在人脐静脉内皮细胞（HUVEC）暴露于不同浓度的二氧化硅纳米粒子（25，50，100，和200 μ g/mL）24小时后。结果表明，二氧化硅纳米颗粒，从50 μ g/mL到200 μ g/mL，显着诱导ROS的产生，线粒体去极化和凋亡的HUVECs。在高浓度时，坏死率、LDH漏出率、CD 54和CD 62 E表达以及TF、IL-6、IL-8和MCP-1的释放均显著增加。二氧化硅纳米颗粒还激活c-Jun N-末端激酶（INK）、c-Jun、p53、caspase-3和NF-κ B，增加Bax表达并抑制Bcl-2蛋白。此外，ROS的抑制减弱了二氧化硅纳米颗粒诱导的细胞凋亡和炎症以及JNK、c-Jun、p53和NF-κ B的活化。总之，我们的研究结果表明，二氧化硅纳米颗粒可以通过氧化应激通过JNK，p53和NF-κ B途径诱导内皮细胞功能障碍，表明暴露于二氧化硅纳米颗粒可能是一个显着的风险，心血管疾病的发展，如动脉粥样硬化和血栓。(C)2010爱思唯尔有限公司版权所有。
Drug carriers are generally introduced into the body intravenously and directly exposed to endothelial cells. Silica nanoparticles could be promising delivery vehicles for drug targeting or gene therapy. However, few studies have been undertaken to determine the biological behavior of silica nanoparticles on endothelial cells. Here we measured reactive oxygen species (ROS) generation, apoptosis and necrosis, proinflammatory and prothrombic properties and the levels of the apoptotic signaling proteins and the transcription factors in human umbilical vein endothelial cells (HUVECs) after exposure to silica nanoparticles of different concentrations (25, 50, 100, and 200 mu g/mL) for 24 h. The results showed that silica nanoparticles, ranging from 50 mu g/mL to 200 mu g/mL, markedly induced ROS production, mitochondrial depolarization and apoptosis in HUVECs. At the highest concentration, the necrotic rate, LDH leakage, the expression of CD54 and CD62E, and the release of TF, IL-6, IL-8 and MCP-1 were significantly increased. Silica nanoparticles also activated c-Jun N-terminal kinase (INK), c-Jun, p53, caspase-3 and NF-kappa B, increased Bax expression and suppressed Bcl-2 protein. Moreover, inhibition of ROS attenuated silica nanoparticles-induced apoptosis and inflammation and the activation of JNK, c-Jun, p53 and NF-kappa B. In summary, our findings demonstrated that silica nanoparticles could induce dysfunction of endothelial cells through oxidative stress via JNK, p53 and NF-kappa B pathways, suggesting that exposure to silica nanoparticles may be a significant risk for the development of cardiovascular diseases such as atherosclerosis and thrombus. (C) 2010 Elsevier Ltd. All rights reserved.