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题名: Crucial Role of P2X(7) Receptor in Regulating Exocytosis of Single-Walled Carbon Nanotubes in Macrophages
作者: Cui, Xuejing; Wan, Bin; Yang, Yu; Ren, Xiaomin; Guo, Liang-Hong; Zhang, Hui
刊名: SMALL
出版日期: 2016-11-16
卷号: 12, 期号:43, 页码:5998-6011
DOI: 10.1002/smll.201602410
部门归属: 环境化学与生态毒理学国家重点实验室
英文摘要: Exocytosis of single-walled carbon nanotubes (SWCNTs) determines therapeutic efficiency and toxicity of nanoproducts but its underlying mechanism remains elusive. In this study, it is found that the exocytosis mechanism of SWCNTs is mediated mainly through the activation of P2X(7) receptor (P2X(7)R), an ATP-gated membrane receptor highly expressed in macrophages. Inhibition of P2X(7)R signaling by either a specific inhibitor (oxidized ATP) or small interfering RNA targeting P2X(7)R largely prevents the exocytosis of SWCNTs from Raw264.7 cells, resulting in significant accumulation of SWCNTs within cells. In contrast, activation of P2X(7)R with ATP promotes exocytosis of SWCNTs. Specifically, it is elucidated that internalized SWCNTs are accumulated in lysosomes and induce transitional release of ATP into extracellular space, which further activates P2X(7)R, leading to the influx of calcium ions, phosphorylation of protein kinase C, ERK1/2, p38, and JNK, as well as alkalization of lysosomes. SWCNTs exposure also induces microtubules reorganization that facilitates the secretion of SWCNTs-containing lysosomes. It is also found that P2X(7)R simultaneously mediates secretion of IL-1 beta from Raw264.7 cells during the process of SWCNTs exocytosis. The combined data reveals that P2X(7)R-mediated pathway is the predominant molecular mechanism for exocytosis of SWCNTs in Raw264.7 cells. Moreover, SWCNT-induced inflammation is closely coupled with the exocytosis of SWCNTs through P2X(7)R.
收录类别: SCI
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内容类型: 期刊论文
URI标识: http://ir.rcees.ac.cn/handle/311016/35825
Appears in Collections:环境化学与生态毒理学国家重点实验室_期刊论文

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