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

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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.

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Abbreviations

HUVECs:

Human umbilical vein vascular endothelial cells

eNOS:

Endothelial nitric oxide synthase

NO:

Nitric oxide

LDH:

Lactate dehydrogenase

AO:

Acridine orange

Ac-LDL:

Acetylated low-density lipoprotein

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Acknowledgments

This study was supported in part by the National 973 Research Project (No. 2010CB933504), the National Natural Science Foundation of China (Nos. 90813022, 81021001, 31070735, 31000510, 31200859, and 20972088), Shandong Province Science & Technology Development Project (2014GSF118136), and Shandong Excellent Young Scientist Award Fund (BS2013SW010).

Conflict of interest

None.

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    Authors and Affiliations

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

      Ning Meng, Zhang Lin & BaoXiang Zhao

    2. School of Biological Science and Technology, University of Jinan, Jinan, 250022, China

      Ning Meng

    3. Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Science, Shandong University, Jinan, 250100, China

      Lei Han, Le Su, Zheng Jiang, Jing Zhao, ShangLi Zhang & JunYing Miao

    4. Key Laboratory of Optoelectronic Materials Chemistry and Physics, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, Fujian, 350002, China

      XiaoHong Pan

    5. The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Shandong University Qilu Hospital, Jinan, 250012, China

      Yun Zhang & JunYing Miao

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    1. Ning Meng
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    Correspondence to BaoXiang Zhao or JunYing Miao.

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    Ning Meng and Lei Han contributed equally to this work.

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    Meng, N., Han, L., Pan, X. et al. Nano-Mg(OH)2-induced proliferation inhibition and dysfunction of human umbilical vein vascular endothelial cells through caveolin-1-mediated endocytosis. Cell Biol Toxicol 31, 15–27 (2015). https://doi.org/10.1007/s10565-014-9291-4

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