Insect resistance to chemical insecticide is a global problem that presents an ongoing threat to sustainable agriculture. Although the increased production of detoxification enzymes has been frequently implicated in resistance development, the mechanisms employed by insecticide-resistant insects for overexpression of these genes remain elusive. Here we report that neuropeptide adipokinetic hormone (AKH) negatively regulates the expression of CYP6ER1 and CYP6AY1, two important cytochrome P450 monooxygenases (P450s) that confer resistance to neonicotinoid imidacloprid in the brown planthopper (BPH). Imidacloprid exposure suppresses AKH synthesis in the susceptible BPH, and AKH is inhibited in the imidacloprid-resistant strain. RNA interference (RNAi) and AKH peptide injection revealed that imidacloprid exposure inhibits the AKH signaling cascade and then provokes reactive oxygen species (ROS) burst. These in turn activate the transcription factors cap ‘n’ collar isoform-C (CncC) and muscle aponeurosis fibromatosis (MafK). RNAi and ROS scavenger assays showed that ROS induces CYP6ER1 expression by activating CncC and MafK, while ROS mediates induction of CYP6AY1 through another unidentified pathway in the resistant BPH. Collectively, these results provide new insights into the regulation of insecticide resistance and implicate both the neuropeptide AKH-mediated ROS burst and transcription factors are involved in the overexpression of P450 detoxification genes in insecticide-resistant insects.

昆虫对化学杀虫剂的抵抗力是一个全球性问题，对可持续农业构成了持续威胁。尽管排毒酶产量的增加经常与耐药性的发展有关，但是抗药性昆虫对这些基因的过度表达所采用的机制仍然难以捉摸。在这里我们报告神经肽脂肪代谢激素（AKH）负调节CYP6ER1和CYP6AY1的表达，这两种重要的细胞色素P450单加氧酶（P450）赋予褐飞虱（BPH）对新烟碱类吡虫啉的抗性。吡虫啉暴露会抑制易感性BPH中的AKH合成，而对吡虫啉耐药的菌株会抑制AKH。RNA干扰（RNAi）和AKH肽注射显示吡虫啉暴露会抑制AKH信号级联反应，然后引发活性氧（ROS）爆发。这些反过来又激活了转录因子帽'n'领亚型-C（CncC）和肌肉腱膜纤维瘤病（MafK）。RNAi和ROS清除剂检测表明，ROS通过激活CncC和MafK诱导CYP6ER1表达，而ROS介导CYP6AY1的诱导。通过抗性BPH中的另一个未知途径。总的来说，这些结果为杀虫剂抗性的调控提供了新的见解，并暗示了神经肽AKH介导的ROS爆发和转录因子都参与了抗杀虫剂昆虫中P450解毒基因的过表达。