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纳米氢氧化镁通过小窝蛋白-1介导的内吞作用抑制人脐静脉血管内皮细胞的增殖并使其功能失调。

Nano-Mg(OH)2-induced proliferation inhibition and dysfunction of human umbilical vein vascular endothelial cells through caveolin-1-mediated endocytosis.

作者信息

Meng Ning, Han Lei, Pan XiaoHong, Su Le, Jiang Zheng, Lin Zhang, Zhao Jing, Zhang ShangLi, Zhang Yun, Zhao BaoXiang, Miao JunYing

机构信息

Institute of Organic Chemistry, School of Chemistry and Chemical Engineering, Shandong University, Jinan, 250100, China.

出版信息

Cell Biol Toxicol. 2015 Feb;31(1):15-27. doi: 10.1007/s10565-014-9291-4. Epub 2015 Jan 10.

Abstract

Nano-Mg(OH)2 is efficiently used in pollutant adsorption and removal due to its high adsorption capability, low-cost, and recyclability. A recent research from our group showed that Mg(OH)2 nanoflakes are not evidently internalized by cancer cells and are not cytotoxic. But the biocompatibility and potential toxicity of nano-Mg(OH)2 in a normal biological system are largely unclear. Nanoparticles could affect the function of endothelial cells, and endothelial dysfunction represents an early sign of lesion within the vasculature. Here, we applied the human umbilical vein vascular endothelial cells (HUVECs) as an in vitro model of the endothelium to study the cytotoxicity of nano-Mg(OH)2. Our results showed that nano-Mg(OH)2 at 200 μg/ml impaired proliferation and induced dysfunction of HUVECs, but did not result in cell necrosis and apoptosis. Transmission electron microscopy images and immunofluorescence results showed that the nano-Mg(OH)2 could enter HUVECs through caveolin-1-mediated endocytosis. Nano-Mg(OH)2 at high concentrations decreased the level of caveolin-1 and increased the activity of endothelial nitric oxide synthase (eNOS), thus leading to the production of excess nitric oxide (NO). In this work, we provide the cell damage concentrations of nano-Mg(OH)2 nanoparticles, and we propose a mechanism of injury induced by nano-Mg(OH)2 in HUVECs.

摘要

纳米氢氧化镁因其高吸附能力、低成本和可回收性而被有效地用于污染物的吸附和去除。我们团队最近的一项研究表明,氢氧化镁纳米片不会明显被癌细胞内化,也没有细胞毒性。但是纳米氢氧化镁在正常生物系统中的生物相容性和潜在毒性在很大程度上尚不清楚。纳米颗粒可能会影响内皮细胞的功能,而内皮功能障碍是血管系统内病变的早期迹象。在此,我们将人脐静脉血管内皮细胞(HUVECs)作为内皮的体外模型来研究纳米氢氧化镁的细胞毒性。我们的结果表明,200μg/ml的纳米氢氧化镁会损害HUVECs的增殖并诱导其功能障碍,但不会导致细胞坏死和凋亡。透射电子显微镜图像和免疫荧光结果表明,纳米氢氧化镁可通过小窝蛋白-1介导的内吞作用进入HUVECs。高浓度的纳米氢氧化镁会降低小窝蛋白-1的水平并增加内皮型一氧化氮合酶(eNOS)的活性,从而导致过量一氧化氮(NO)的产生。在这项工作中,我们提供了纳米氢氧化镁纳米颗粒的细胞损伤浓度,并提出了纳米氢氧化镁诱导HUVECs损伤的机制。

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