https://scholars.lib.ntu.edu.tw/handle/123456789/626401
標題: | Gold Nanoparticles Increase Endothelial Paracellular Permeability by Altering Components of Endothelial Tight Junctions, and Increase Blood-Brain Barrier Permeability in Mice | 作者: | Li, Ching-Hao MING-KWANG SHYU Jhan, Cheng Cheng, Yu-Wen Tsai, Chi-Hao Liu, Chen-Wei Lee, Chen-Chen Chen, Ruei-Ming JAW-JOU KANG |
關鍵字: | blood-brain barrier; endothelial barrier; paracellular permeability; protein kinase C zeta (PKCζ); tight junction | 公開日期: | 十一月-2015 | 出版社: | OXFORD UNIV PRESS | 卷: | 148 | 期: | 1 | 起(迄)頁: | 192 | 來源出版物: | Toxicological sciences : an official journal of the Society of Toxicology | 摘要: | Gold nanoparticles (Au-NPs) are being increasingly used as constituents in cosmetics, biosensors, bioimaging, photothermal therapy, and targeted drug delivery. This elevated exposure to Au-NPs poses systemic risks in humans, particularly risks associated with the biodistribution of Au-NPs and their potent interaction with biological barriers. We treated human umbilical vein endothelial cells with Au-NPs and comprehensively examined the expression levels of tight junction (TJ) proteins such as occludin, claudin-5, junctional adhesion molecules, and zonula occludens-1 (ZO-1), as well as endothelial paracellular permeability and the intracellular signaling required for TJ organization. Moreover, we validated the effects of Au-NPs on the integrity of TJs in mouse brain microvascular endothelial cells in vitro and obtained direct evidence of their influence on blood-brain barrier (BBB) permeability in vivo. Treatment with Au-NPs caused a pronounced reduction of PKCζ-dependent threonine phosphorylation of occludin and ZO-1, which resulted in the instability of endothelial TJs and led to proteasome-mediated degradation of TJ components. This impairment in the assembly of TJs between endothelial cells increased the permeability of the transendothelial paracellular passage and the BBB. Au-NPs increased endothelial paracellular permeability in vitro and elevated BBB permeability in vivo. Future studies must investigate the direct and indirect toxicity caused by Au-NP-induced endothelial TJ opening and thereby address the double-edged-sword effect of Au-NPs. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/626401 | ISSN: | 1096-6080 | DOI: | 10.1093/toxsci/kfv176 |
顯示於: | 醫學系 |
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