Jiangsu Key Laboratory for Biodiversity and Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing 210023, China.
Gene. 2021 Feb 15;769:145213. doi: 10.1016/j.gene.2020.145213. Epub 2020 Oct 15.
The small GTPase Ran has a variety of biological functions, one of the most prominent of which is to regulate nucleocytoplasmic transport. In our previous study, it was suggested that Ran is involved in the deltamethrin (DM) stress. In addition, Keap1-Nrf2-ARE pathway was also confirmed to be associated with DM stress. We report here that under DM stress, interfering Ran or nuclear transport factor Ntf2 by RNAi could suppress the nuclear import of nuclear transcription factor Nrf2 which then down-regulates the expressions of detoxification enzyme genes (Cyp4d20, Cyp4ae1, GstD5, Sod3, etc.), ultimately resulting in a significant apoptosis of Drosophila Kc cells. In contrast, after overexpressing Ran in Kc cells, Nrf2 has a higher concentration in the nucleus, and the expressions of detoxification enzyme genes are up-regulated, while the DM-induced apoptosis is significantly lower than that of the control group. Additionally, we preliminary found silencing Ntf2 or Ran could prevent the nuclear import of transcription factor Dif under DM stress, subsequently decreased expressions of antimicrobial peptide genes (Drsl1). In summary, our data mainly indicates that Ran may participate in DM stress through regulating the nuclear import of Nrf2, which could help to study the mechanism of deltamethrin resistance.
小分子 GTP 酶 Ran 具有多种生物学功能，其中最突出的功能之一是调节核质转运。在我们之前的研究中，表明 Ran 参与了溴氰菊酯（DM）应激。此外，Keap1-Nrf2-ARE 通路也被证实与 DM 应激有关。我们在这里报告，在 DM 应激下，通过 RNAi 干扰 Ran 或核转运因子 Ntf2 可以抑制核转录因子 Nrf2 的核内输入，从而下调解毒酶基因（Cyp4d20、Cyp4ae1、GstD5、Sod3 等）的表达，最终导致果蝇 Kc 细胞发生明显的凋亡。相比之下，在 Kc 细胞中过度表达 Ran 后，Nrf2 在核内的浓度更高，解毒酶基因的表达上调，而 DM 诱导的凋亡明显低于对照组。此外，我们初步发现，在 DM 应激下，沉默 Ntf2 或 Ran 可以阻止转录因子 Dif 的核内输入，随后降低抗菌肽基因（Drsl1）的表达。总之，我们的数据主要表明，Ran 可能通过调节 Nrf2 的核内输入参与 DM 应激，这有助于研究溴氰菊酯抗性的机制。
