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.

Abbreviatioin: DM, deltamethrin

小GTPase Ran具有多种生物学功能，其中最突出的功能之一就是调节核质运输。在我们先前的研究中，有人建议Ran参与溴氰菊酯（DM）应激。另外，还证实了Keap1-Nrf2-ARE途径与DM应激有关。我们在此报告，在DM胁迫下，RNAi干扰Ran或核转运因子Ntf2可以抑制核转录因子Nrf2的核输入，然后下调解毒酶基因（Cyp4d20，Cyp4ae1，GstD5，Sod3等）的表达。 ，最终导致果蝇明显凋亡Kc细胞。相反，在Kc细胞中过表达Ran后，Nrf2在细胞核中的浓度更高，并且解毒酶基因的表达被上调，而DM诱导的细胞凋亡明显低于对照组。此外，我们初步发现沉默Ntf2或Ran可以阻止DM胁迫下转录因子Dif的核输入，从而降低抗菌肽基因（Drsl1）的表达。总之，我们的数据主要表明Ran可能通过调节Nrf2的核输入来参与DM应激，这可能有助于研究溴氰菊酯抗性的机制。

缩写： DM，溴氰菊酯