CAS Key Lab of Bio-Medical Diagnostics, Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou, Jiangsu 215163, PR China; Academy for Engineering & Technology, Fudan University, Shanghai 200433, PR China.
School of Biology & Basic Medical Sciences, Medical College, Soochow University, Suzhou, Jiangsu 215123, PR China.
Environ Pollut. 2019 Jan;244:588-599. doi: 10.1016/j.envpol.2018.10.092. Epub 2018 Oct 22.
Adenosine triphosphate-binding cassette (ABC) transporters, including P-glycoprotein (Pgp) and multi-resistance associated proteins (Mrps), have been considered important participants in the self-protection of zebrafish embryos against environmental pollutants, but their possible involvement in the efflux and detoxification of quantum dots (QDs), as well as their regulation mechanism are currently unclear. In this work, gene expression alterations of ABC transporters, nuclear receptors, and oxidative stress signaling in zebrafish embryos after the treatment of mercaptopropionic acid (MPA)CdTe QDs and MPA-CdSCdTe QDs were investigated. It was observed that both QDs caused concentration-dependent delayed hatching effects and the subsequent induction of transporters like mrp1&2 in zebrafish embryos, indicating the protective role of corresponding proteins against CdTe QDs. Accompanying these alterations, expressions of nuclear receptors including the pregnane X receptor (pxr), aryl hydrocarbon receptor (ahr) 1b, and peroxisome proliferator-activated receptor (ppar)-β were induced by QDs in a concentration- and time-dependent manner. Moreover, elevated oxidative stress, reflected by the reduction of glutathione (GSH) level and superoxide dismutase (SOD) activities, as well as the dramatic induction of nuclear factor E2 related factor (nrf) 2, was also found. More importantly, alterations of pxr and nrf2 were more pronounced than that of mrps, and these receptors exhibited an excellent correlation with delayed hatching rate in the same embryos (R > 0.8). Results from this analysis demonstrated that the induction of mrp1 and mrp2 could be important components for the detoxification of QDs in zebrafish embryos. These transporters could be modulated by nuclear receptors and oxidative stress signaling. In addition, up-regulation of pxr and nrf2 could be developed as toxic biomarkers of CdTe QDs.
三磷酸腺苷结合盒（ABC）转运蛋白，包括 P 糖蛋白（Pgp）和多药耐药相关蛋白（Mrps），被认为是斑马鱼胚胎自身抵御环境污染物的重要参与者，但它们在量子点（QDs）的外排和解毒中的可能作用及其调节机制目前尚不清楚。在这项工作中，研究了巯基丙酸（MPA）CdTe QDs 和 MPA-CdSCdTe QDs 处理后斑马鱼胚胎中 ABC 转运蛋白、核受体和氧化应激信号的基因表达变化。结果发现，两种 QD 均导致斑马鱼胚胎出现浓度依赖性的延迟孵化效应，并随后诱导 mrp1&2 等转运蛋白的表达，表明相应蛋白对 CdTe QD 具有保护作用。伴随着这些变化，核受体如孕烷 X 受体（pxr）、芳香烃受体（ahr）1b 和过氧化物酶体增殖物激活受体（ppar）-β 的表达也被 QD 以浓度和时间依赖的方式诱导。此外，还发现氧化应激水平升高，表现为谷胱甘肽（GSH）水平和超氧化物歧化酶（SOD）活性降低，核因子 E2 相关因子（nrf）2 显著诱导。更重要的是，pxr 和 nrf2 的变化比 mrps 更为明显，并且这些受体与同一胚胎中的延迟孵化率表现出良好的相关性（R>0.8）。该分析的结果表明，mrp1 和 mrp2 的诱导可能是斑马鱼胚胎中 QD 解毒的重要组成部分。这些转运蛋白可以被核受体和氧化应激信号调节。此外，pxr 和 nrf2 的上调可以作为 CdTe QD 的毒性生物标志物。
