Endoplasmic reticulum stress-related calcium imbalance plays an important role on Zinc oxide nanoparticles-induced failure of neural tube closure during embryogenesis.
Endoplasmic reticulum stress-related calcium imbalance plays an important role on Zinc oxide nanoparticles-induced failure of neural tube closure during embryogenesis.
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内质网应激相关的钙失衡在氧化锌纳米颗粒诱导的胚胎发生过程中神经管闭合失败中起着重要作用。
DOI：
10.1016/j.envint.2021.106495
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发表时间：
2021-03
影响因子：
11.8
通讯作者：
Yang Xuesong
中科院分区：
文献类型：
--
作者：
Yan Yu;Wang Guang;Luo Xin;Zhang Ping;Peng Shuang;Cheng Xin;Wang Mengwei;Yang Xuesong
氧化锌纳米颗粒（ZnO NPs）在农业、食品、化妆品等领域得到了越来越广泛的应用。然而，氧化锌纳米粒子在其生产、使用和处置的各个阶段都对生态环境和公众健康产生了不同程度的不利影响。氧化锌NPs可以被孕妇摄入并通过胎盘屏障转移到发育中的胚胎/胎儿中，但氧化锌NPs对胚胎和胎儿发育的潜在毒性在很大程度上尚不清楚。在本研究中，我们发现ZnO NPs暴露导致小鼠和鸡胚胎神经管闭合的生长成比例衰竭，同时鸡胚胎发育中的神经管凋亡增加，这在SH-SY5Y细胞系的体外实验中得到了证实。此外，EDTA去除游离Zn2+离子或cacl2抑制Zn2+离子吸收可部分减轻ZnO NPs诱导的神经毒性，这表明ZnO NPs诱导的发育性神经毒性可能是由ZnO NPs和ZnO NPs释放的Zn2+离子共同作用的。此外，我们发现ZnO NPs暴露引起内质网应激介导的凋亡主要是由细胞内钙（Ca2+）浓度的增加驱动的，而不是由三种膜蛋白受体（ATF6， re -1和PERK）的激活驱动的。因此，氧化锌NPs暴露下Ca2+失衡介导的细胞凋亡可能导致神经前体发育中的细胞功能障碍，如神经管闭合异常，最终导致胚胎发生过程中的神经管缺陷（NTDs）。综上所述，我们的研究结果表明，ZnO NPs暴露大大增加了发育中的胚胎中内质网应激介导的神经细胞死亡导致神经管关闭失败的风险，这可能进一步导致胎儿期NTD，包括神经管关闭失败。
Zinc oxide nanoparticles (ZnO NPs) have been increasingly and widely utilized in various fields, such as agriculture, food and cosmetics. However, various levels of adverse impacts of ZnO NPs on the ecological environment and public health have been associated with each stage of their production, use and disposal. ZnO NPs can be ingested by pregnant women and transferred to developing embryos/foetus through the placental barrier, however, the potential toxicity of ZnO NPs to embryonic and foetal development is largely unclear. In this study, we discovered that ZnO NPs exposure caused growth proportional failure of neural tube closure in mouse and chicken embryos and a simultaneous increase in apoptosis in the developing neural tubes of chicken embryos, which was verified in anin vitroexperiment using the SH-SY5Y cell line. Furthermore, removal of free Zn2+ions with EDTA or inhibition of Zn2+ion absorption by CaCl2partially alleviated the neurotoxicity induced by ZnO NPs, implying that ZnO NPs-induced developmental neurotoxicity is probably due to both ZnO NPs and the Zn2+ions released from ZnO NPs. In addition, we found that ZnO NPs exposure caused endoplasmic reticulum stress-mediated apoptosis driven mainly by an increase in intracellular calcium (Ca2+) concentrations, rather than by the activation of three membrane protein receptors (ATF6, IRE-1 and PERK). Thus, Ca2+imbalance-mediated apoptosis in the context of ZnO NPs exposure may lead to cellular dysfunctions in developing neural precursors, such as, abnormalities involved in neural tube closure, ultimately leading to neural tube defects (NTDs) during embryogenesis. In sum, our results revealed that ZnO NPs exposure greatly increases the risk of failure of neural tube closure through endoplasmic reticulum stress-mediated neural cell death in the developing embryos, which may further lead to the NTD in fetal stage, including failure of neural tube closure.
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影响因子：
3.4
作者：
Jingxia Zhao;Lanju Xu;Tao Zhang;G. Ren;Zhuo Yang
通讯作者：
Jingxia Zhao;Lanju Xu;Tao Zhang;G. Ren;Zhuo Yang
影响因子：
2.5
作者：
Lin, Weisheng;Xu, Yi;Huang, Yue-Wern
通讯作者：
Huang, Yue-Wern
影响因子：
64.8
作者：
Fimia, Gian Maria;Stoykova, Anastassia;Cecconi, Francesco
通讯作者：
Cecconi, Francesco
影响因子：
4.3
作者：
Guang Wang;Wen-qing Huang;Shu-dan Cui;Shuai Li;Xiao-yu Wang;Yan Li;Manli Chuai;Liu Cao;Jiangchao Li;Da-xiang Lu;Xuesong Yang
通讯作者：
Guang Wang;Wen-qing Huang;Shu-dan Cui;Shuai Li;Xiao-yu Wang;Yan Li;Manli Chuai;Liu Cao;Jiangchao Li;Da-xiang Lu;Xuesong Yang
影响因子：
4.1
作者：
Lopes, Silvia;Ribeiro, Fabianne;Loureiro, Susana
通讯作者：
Loureiro, Susana