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凋亡途径在新鲜和老化氧化锌纳米颗粒诱导的细胞毒性中的作用

The Role of Apoptosis Pathway in the Cytotoxicity Induced by Fresh and Aged Zinc Oxide Nanoparticles.

作者信息

Wang Juan, Wang Lei, Zhao Wenting, Yu Na, Cheng Meiling, Su Mingqin, Hu Jian, Wu Xiaoyan, Du Hua, Wang Meimei

机构信息

Department of Pathophysiology, School of Basic Medical Science, Anhui Medical University, No. 81, Mei-Shan Road, Hefei, 230032, Anhui, People's Republic of China.

MOE Key Laboratory of Population Health Across Life Cycle, No. 81, Mei-Shan Road, Hefei, 230032, Anhui, People's Republic of China.

出版信息

Nanoscale Res Lett. 2021 Aug 9;16(1):129. doi: 10.1186/s11671-021-03587-y.

DOI:10.1186/s11671-021-03587-y
PMID:34370102
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8353024/
Abstract

Zinc oxide nanoparticles (ZnO NPs) are used in a wide range of applications including industry, commercial products and medicine field. Numerous mechanistic studies for ZnO NPs' toxicity were performed on pristine (fresh) NPs. However, the cytotoxicity induced by the transformed (aged) ZnO NPs and the underlying mechanisms remain unclear. Here, we observed the physicochemical transformation of ZnO NPs underwent over time, followed by evaluating the cytotoxicity of fresh and aged NPs. We found that fresh ZnO NPs induced higher apoptosis level than their aged counterparts. Accordingly, RNA sequencing data from aged ZnO NP-treated human-hamster hybrid (A) cells showed that p53, PI3k-Akt, FoXO, Glutathione, ErbB, HIF-1, Oxytocin and Jak-STAT signaling pathways were enriched but no apoptosis pathway. Quantitative PCR results revealed the significantly higher mRNA level of IL1B and CD69 in fresh NP-treated groups compared to that of aged ZnO NP- and zinc chloride-treated groups. The above results indicated that the lower cytotoxicity of aged ZnO NPs is partially attributed to their reduced potency in inducing apoptosis. The transcriptional regulation of multiple signal pathways activated by aged NPs may help to build the cellular homeostasis. Taken together, our findings highlight the influence of aging (environmental transformation) process of ZnO NPs on their toxicities and biological consequences.

摘要

氧化锌纳米颗粒（ZnO NPs）被广泛应用于包括工业、商业产品和医学领域在内的众多领域。许多关于ZnO NPs毒性的机制研究都是针对原始（新鲜）纳米颗粒进行的。然而，转化（老化）的ZnO NPs诱导的细胞毒性及其潜在机制仍不清楚。在此，我们观察了ZnO NPs随时间的物理化学转变，随后评估了新鲜和老化纳米颗粒的细胞毒性。我们发现，新鲜的ZnO NPs比老化的ZnO NPs诱导更高水平的细胞凋亡。相应地，来自老化ZnO NP处理的人-仓鼠杂交（A）细胞的RNA测序数据显示，p53、PI3k-Akt、FoxO、谷胱甘肽、ErbB、HIF-1、催产素和Jak-STAT信号通路富集，但没有凋亡通路。定量PCR结果显示，与老化ZnO NP和氯化锌处理组相比，新鲜NP处理组中IL1B和CD69的mRNA水平显著更高。上述结果表明，老化ZnO NPs较低的细胞毒性部分归因于其诱导细胞凋亡的能力降低。老化纳米颗粒激活的多种信号通路的转录调控可能有助于建立细胞内稳态。综上所述，我们的研究结果突出了ZnO NPs老化（环境转变）过程对其毒性和生物学后果的影响。

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