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题名: Insight into the Mechanisms of Combined Toxicity of Single-Walled Carbon Nanotubes and Nickel Ions in Macrophages: Role of P2X(7) Receptor
作者: Cui, Xuejing; Wan, Bin; Guo, Liang-Hong; Yang, Yu; Ren, Xiaomin
刊名: ENVIRONMENTAL SCIENCE & TECHNOLOGY
出版日期: 2016-11-15
卷号: 50, 期号:22, 页码:12473-12483
DOI: 10.1021/acs.est.6b03842
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: Coexistence of nanomaterials and environmental pollutants requires in-depth understanding of combined toxicity and underlying mechanism. In this work, we found that coexposure to the mixture of noncytotoxic level of single-walled carbon nanotubes (SWCNTs) (10 mu g/mL) and Ni2+ (20 mu M) induced significant cytotoxicity in macrophages. However, almost equal amount of intracellular Ni2+ was detected after Ni2+/SWCNT coexposure or Ni2+ single exposure, indicating no enhanced cellular uptake of Ni2+ occurred. SDS-PAGE analysis revealed 50% more SWCNTs retained in Ni2+/SWCNT exposed cells than that with SWCNT exposure alone, regardless of the exposure sequence (coexposure, Ni2+ pre- or post-treatment), suggesting inhibited SWCNT exocytosis by Ni2+. The increased cellular dose of SWCNTs could quantitatively account for the elevated toxicity of Ni2+/SWCNT mixture to cells. It was then found that agonist (ATP) and antagonist (o-ATP) of P2X(7)R could regulate intracellular SWCNT amount and the cytotoxicity accordingly. In addition, inhibition of P2X(7)R by P2X(7)-targeting siRNA diminished the inhibitory effect of Ni2+. It was therefore concluded that Ni2+ impeded SWCNT exocytosis by inhibiting P2X(7)R, leading to higher intracellular retention of SWCNTs and elevated cytotoxicity. Our work identified exocytosis inhibition as an important mechanism for SWCNT/Ni2+ toxicity, and revealed the crucial role of P2X(7)R. in mediating such inhibitory effect.
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/311016/35877
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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Recommended Citation:
Cui, Xuejing,Wan, Bin,Guo, Liang-Hong,et al. Insight into the Mechanisms of Combined Toxicity of Single-Walled Carbon Nanotubes and Nickel Ions in Macrophages: Role of P2X(7) Receptor[J]. ENVIRONMENTAL SCIENCE & TECHNOLOGY,2016,50(22):12473-12483.
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文件名: Insight into the Mechanisms of Combined Toxicity of Single-Walled Carbon Nanotubes and Nickel Ions in Macrophages Role of P2X(7) Receptor.pdf
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