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Nrf2-Keap1 通路:果蝇 Kc 细胞对抗杀虫剂迫害的秘密武器。

The Nrf2-Keap1 pathway: A secret weapon against pesticide persecution in Drosophila Kc cells.

机构信息

Jiangsu Key Laboratory for Biodiversity and Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing 210023, China.

Institute of Plant Protection, Guizhou Academy of Agricultural Sciences, Guiyang 550009, China.

出版信息

Pestic Biochem Physiol. 2020 Mar;164:47-57. doi: 10.1016/j.pestbp.2019.12.008. Epub 2019 Dec 30.

DOI:10.1016/j.pestbp.2019.12.008
PMID:32284136
Abstract

Nrf2-Keap1 pathway defends organisms against the detrimental effects of oxidative stress, and play pivotal roles in preventing xenobiotic-related toxicity. We designed experiments to explore and verify its role and function under deltamethrin (DM) stress. In experiments, DM was selected as the inducer, and Drosophila Kc cells were treated as the objects. The result showed the oxidative stress of cells proliferated in a very short time after DM treatment, reaching the maximum after one hour of treatment. The experimental data showed Nrf2 could be up-regulated and activated by DM which were manifested by the increase of Nrf2 mRNA, Nrf2 protein in the nucleus and the expression of detoxification enzyme genes. We further tested the activity of all groups, and found the survival rate of cells was basically proportional to the expression of Nrf2. Based on the above experimental results, Keap1 overexpression (K+), Nrf2 overexpression (N+) or interference (N-) cells were used to verified the relationship between Nrf2, cell survival and detoxification enzymes expression. We found the cell survival rate of N+ group was significantly higher than that of other groups and the expression of detoxification enzymes were increased compared to the control group. These results demonstrated that Nrf2 is related to cell detoxification and associated with the tolerance to DM. Our evidence suggested Nrf2 is a potential therapeutic target for oxidative stress and a potential molecular target gene of resistance control.

摘要

Nrf2-Keap1 通路防御机体免受氧化应激的有害影响,并在预防外源性化学物质相关毒性方面发挥关键作用。我们设计实验来探索和验证其在溴氰菊酯(DM)应激下的作用和功能。在实验中,选择 DM 作为诱导剂,以 Drosophila Kc 细胞作为处理对象。结果表明,细胞在 DM 处理后很短的时间内就会发生氧化应激,在处理 1 小时后达到最大值。实验数据表明,DM 可以上调和激活 Nrf2,这表现在 Nrf2 mRNA、核内 Nrf2 蛋白和解毒酶基因的表达增加。我们进一步测试了所有组的活性,发现细胞的存活率基本与 Nrf2 的表达成正比。基于上述实验结果,使用 Keap1 过表达(K+)、Nrf2 过表达(N+)或干扰(N-)细胞来验证 Nrf2、细胞存活和解毒酶表达之间的关系。我们发现 N+组的细胞存活率明显高于其他组,且与对照组相比,解毒酶的表达增加。这些结果表明,Nrf2 与细胞解毒有关,并与对 DM 的耐受性有关。我们的证据表明,Nrf2 是氧化应激的潜在治疗靶点,也是抗性控制的潜在分子靶标基因。

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