Crucial Role of P2X(7) Receptor in Regulating Exocytosis of Single-Walled Carbon Nanotubes in Macrophages

CORC > 生态环境研究中心 > 中国科学院生态环境研究中心 > 环境化学与生态毒理学国家重点实验室

	Crucial Role of P2X(7) Receptor in Regulating Exocytosis of Single-Walled Carbon Nanotubes in Macrophages
	Cui, Xuejing; Wan, Bin; Yang, Yu; Ren, Xiaomin; Guo, Liang-Hong; Zhang, Hui
刊名	SMALL
	2016-11-16
卷号	12 期号:43 页码:5998-6011
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
内容类型	期刊论文
源URL	[http://ir.rcees.ac.cn/handle/311016/35825]
专题	生态环境研究中心_环境化学与生态毒理学国家重点实验室
推荐引用方式 GB/T 7714	Cui, Xuejing,Wan, Bin,Yang, Yu,et al. Crucial Role of P2X(7) Receptor in Regulating Exocytosis of Single-Walled Carbon Nanotubes in Macrophages[J]. SMALL,2016,12(43):5998-6011.
APA	Cui, Xuejing,Wan, Bin,Yang, Yu,Ren, Xiaomin,Guo, Liang-Hong,&Zhang, Hui.(2016).Crucial Role of P2X(7) Receptor in Regulating Exocytosis of Single-Walled Carbon Nanotubes in Macrophages.SMALL,12(43),5998-6011.
MLA	Cui, Xuejing,et al."Crucial Role of P2X(7) Receptor in Regulating Exocytosis of Single-Walled Carbon Nanotubes in Macrophages".SMALL 12.43(2016):5998-6011.