Cd exposure confers β-cypermethrin tolerance in Lymantria dispar by activating the ROS/CnCC signaling pathway-mediated P450 detoxification

• Published in: Journal of hazardous materials 2024-10, Vol.478, p.135566, Article 135566
• Main Authors: Tan, Mingtao, Jiang, Hong, Chai, Rusong, Fan, Miao, Niu, Zengting, Sun, Guotong, Yan, Shanchun, Jiang, Dun
• Format: Article
• Language: English
• Subjects: Animals; Cadmium; Cadmium - toxicity; Cross-tolerance; Cytochrome P-450 Enzyme System - genetics; Cytochrome P-450 Enzyme System - metabolism; Flighted Spongy Moth Complex; Inactivation, Metabolic; Insect Proteins - genetics; Insect Proteins - metabolism; Insecticide; Insecticide Resistance - genetics; Insecticides - pharmacology; Insecticides - toxicity; Larva - drug effects; Larva - metabolism; Lymantria dispar; Moths - drug effects; Moths - metabolism; Pyrethrins - pharmacology; Pyrethrins - toxicity; Reactive Oxygen Species - metabolism; Signal Transduction - drug effects; Transcription Factors - genetics; Transcription Factors - metabolism; Transcriptional regulatory mechanism
• ISSN: 0304-3894; 1873-3336; 1873-3336
• DOI: 10.1016/j.jhazmat.2024.135566

Heavy metal pollutants are important abiotic environmental factors affecting pest habitats. In this study, Cd pre-exposure significantly increased the tolerance of Lymantria dispar larvae to β-cypermethrin, but did not significantly alter their tolerance to λ-cyhalothrin and bifenthrin. The activation of P450 by Cd exposure is the key mechanism that induces insecticide cross-tolerance in L. dispar larvae. Both before and after β-cypermethrin treatment, Cd exposure significantly increased the expression of CYP6AB224 and CYP6AB226 in L. dispar larvae. Silencing CYP6AB224 and CYP6AB226 reduced the tolerance of Cd-treated L. dispar larvae to β-cypermethrin. Transgenic CYP6AB224 and CYP6AB226 genes significantly increased the tolerance of Drosophila and Sf9 cells to β-cypermethrin, and the recombinant proteins of both genes could significantly metabolise β-cypermethrin. Cd exposure significantly increased the expression of CnCC and Maf. CnCC was found to be a key transcription factor regulating CYP6AB224- and CYP6AB226-activated insecticide cross-tolerance in Cd-treated larvae. Decreasing reactive oxygen species (ROS) levels in the Cd-treated larvae or increasing ROS levels in the untreated larvae reduced or enhanced the expression of CnCC, CYP6AB224 and CYP6AB226 and β-cypermethrin tolerance in L. dispar larvae, respectively. Collectively, Cd exposure confers β-cypermethrin tolerance in L. dispar larvae through the ROS/CnCC signalling pathway-mediated P450 detoxification. [Display omitted] •Cd pre-exposure enhanced the cross-tolerance of L. dispar larvae to β-cypermethrin.•Cd pre-exposure activated the P450 detoxification system of L. dispar larvae.•CYP6AB224 and CYP6AB226 were key detoxify genes to the formation of cross-tolerance.•ROS-CnCC signaling pathway was proved to be responsible for activation of detoxify genes.