The critical role of nanoparticle sizes in the interactions between gold nanoparticles and ABC transporters in zebrafish embryos
The critical role of nanoparticle sizes in the interactions between gold nanoparticles and ABC transporters in zebrafish embryos
复制标题
纳米颗粒尺寸在斑马鱼胚胎中金纳米颗粒和 ABC 转运蛋白相互作用中的关键作用。
DOI：
10.1016/j.aquatox.2022.106286
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发表时间：
2022-09-06
影响因子：
4.5
通讯作者：
Yin，Jian
中科院分区：
文献类型：
--
作者：
Hu，Jia;Tian，Jingjing;Yin，Jian
尽管越来越多的证据表明三磷酸腺苷结合盒（ABC转运体）介导的纳米颗粒外溢，但这些现象的普遍性和该过程的决定因素仍有待阐明。本文旨在系统研究纳米颗粒大小在斑马鱼胚胎中三磷酸腺苷结合盒（ABC转运体）与金纳米颗粒（AuNPs, 3 nm， 19 nm和84 nm，分别命名为Au-3， Au-19和Au-84）相互作用中的作用。结果表明，3种AuNPs均具有显著的毒性，表现为延迟胚胎孵化、降低谷胱甘肽（GSH）含量、增加活性氧（ROS）水平。在胚胎绒毛膜的阻碍下，较小的AuNPs更容易在胚胎中积累，毒性更高。转运体抑制剂的加入增强了Au-3和Au-19的积累和毒性，并且这些纳米颗粒诱导了abcc2和abcb4的表达，这表明Au-3和Au-19是ABC转运体的潜在底物，但这些现象在Au-84中几乎没有发现。相反，Au-84抑制abcc1、abcg5、abc8等多种ABC转运蛋白的基因表达。对于特异性抑制因子，转录因子如核因子-红细胞2相关因子-2 （Nrf2）和妊娠X受体（Pxr）在AuNPs诱导ABC转运蛋白中起重要作用。毕竟，这些结果揭示了纳米颗粒大小在斑马鱼胚胎中ABC转运蛋白和aunp之间的相互作用中起着至关重要的作用，而临界尺寸可能在19纳米左右。这些信息将有助于评估纳米颗粒的环境风险，以及它们与其他化学毒物的相互作用。
Despite the increasing evidences for adenosine triphosphate-binding cassette (ABC transporters)-mediated efflux of nanoparticles, the universality of these phenomena and the determining factors for the process remained to be clarified. This paper aimed to systemically investigate the role of nanoparticle size in the interactions between adenosine triphosphate-binding cassette (ABC transporters) and gold nanoparticles (AuNPs, 3 nm, 19 nm, and 84 nm, named as Au-3, Au-19, and Au-84) in zebrafish embryos. The results showed that all the three AuNPs induced significant toxicity as reflected by delayed hatching of embryos, decreased glutathione (GSH) contents, and increased reactive oxygen species (ROS) levels. Under the hindrance of embryo chorions, smaller AuNPs could more easily accumulate in the embryos, causing higher toxicity. Addition of transporter inhibitors enhanced the accumulation and toxicity of Au-3 and Au-19, and these nanoparticles induced the expressions ofabcc2andabcb4, indicating a fact that Au-3 and Au-19 were the potential substrates of ABC transporters, but these phenomena were barely found for Au-84. On the contrary, Au-84 suppressed the gene expressions of various ABC transporters likeabcc1, abcg5,andabcg8. With specific suppressors, transcription factors like nuclear factor-erythroid 2-related factor-2 (Nrf2) and pregnane X receptor (Pxr) were found to be important in the induction of ABC transporters by AuNPs. After all, these results revealed a vital role of nanoparticle sizes in the interactions between ABC transporters and AuNPs in zebrafish embryos, and the critical size could be around 19 nm. Such information would be beneficial in assessing the environmental risk of nanoparticles, as well as their interactions with other chemical toxicants.