Nuclear receptor HR96 up‐regulates cytochrome P450 for insecticide detoxification in Tribolium castaneum

Abstract

BACKGROUND: Red flour beetle, Tribolium castaneum (T. castaneum), is a major agricultural pest that causes significant damage to stored grains and products. Although hormone receptor 96 (HR96) is known to be the single ortholog corresponding to mammalian constitutive androstane receptor and pregnane X receptor, the structural features of Tribolium HR96 (TcHR96) and its role in insecticide-mediated transcription control of cytochrome P450 enzyme genes in T. castaneum have not been elucidated yet.RESULTS: We cloned full-length complementary DNA encoding TcHR96 and revealed the role of TcHR96 in transcriptional control of cytochrome P450 enzyme genes. Interestingly, genome-wide transcriptome analysis of HR96-deficient beetles using RNA sequencing showed a positive correlation between TcHR96 and gene transcription of metabolizing enzymes involved in phase I detoxification processes. Moreover, TcHR96 overexpression significantly increased the promoter activity of genes encoding phase I P450 enzymes such as CYP4Q4, CYP4G7, CYP4BR3, and CYP345A1. Chromatin immunoprecipitation analysis showed that TcHR96 could directly bind to the promoter of gene encoding CYP345A1, an enzyme for metabolizing insecticides in T. castaneum. Furthermore, imidacloprid, a neonicotinoid insecticide, significantly increased gene expression of phase I P450 enzymes in old larvae of T. castaneum, which were reversed by TcHR96 knockdown. Finally, TcHR96 knockdown significantly decreased the resistance of old larvae to imidacloprid concomitant with reduction of imidacloprid-mediated phase I P450 enzyme gene expression.CONCLUSION: TcHR96 plays a major role in transcriptional control of P450 enzyme for imidacloprid detoxification. Controlling TcHR96 might facilitate the regulation of insecticide tolerance in T. castaneum, thus providing a promising new strategy to manage pest beetle populations.

CYP321A Subfamily P450s Contribute to the Detoxification of Phytochemicals and Pyrethroids in Spodoptera litura

“…While numerous studies have documented transcriptional responses of P450s to xenobiotics, including phytochemicals and insecticides, the mechanisms underlying the regulation of enhanced enzymatic detoxification are still poorly understood. ,, Several signaling pathways involved in xenobiotic response have been identified by recent studies using advanced genetic tools, and upregulation or activation of some components of these pathways has been linked to the transcriptional regulation of detoxification genes. ,− Among them, CncC and its partner Maf have been implicated in the regulation of a battery of detoxification genes associated with insecticide resistance, as well as phytochemical adaptation. − In this study, CncC and MafK were significantly induced by flavone, xanthotoxin, coumarin, and λ-cyhalothrin, which is in accordance with the induced expression patterns of the CYP321A subfamily genes. In view of our recent findings that CncC regulates 80% of the detoxification genes induced by flavone and upregulation of CYP6AB12 conferring tolerance of S.…”

A Comparative Study of Transcriptional Regulation Mechanism of Cytochrome P450 CYP6B7 between Resistant and Susceptible Strains of Helicoverpa armigera

“…A previous study reported that transcription factor AP1 can mediate the overexpression of CYP6ER1 to regulate the resistance of Nilaparvata lugens to clothianidin . Nuclear receptor HR96 up-regulates the expression levels of CYP4Q4 , CYP4G7 , CYP4BR3 , and CYP345A1 that play important role in the detoxification of T. castaneum to imidacloprid . Transcription factor AhR/ARNT regulates the expression levels of CYP6CY3 and CYP6CY4 , and plays a role in the adaptation of Myzus persicae nicotianae to nicotine .…”

“…36 Nuclear receptor HR96 up-regulates the expression levels of CYP4Q4, CYP4G7, CYP4BR3, and CYP345A1 that play important role in the detoxification of T. castaneum to imidacloprid. 37 Transcription factor AhR/ARNT regulates the expression levels of CYP6CY3 and CYP6CY4, and plays a role in the adaptation of Myzus persicae nicotianae to nicotine. 38 In the present study, the M3, M4, and M7 sites in CYP6B7 promoter of HDTJFR were located in a predicted binding site of transcription factors Ubx/ Otp, Zen2, Ara/Br, respectively, and Ubx and Br were overexpressed in the HDTJFR strain.…”

Multi-Omics Techniques for Analysis Antifungal Mechanisms of Lipopeptides Produced by Bacillus velezensis GS-1 against Magnaporthe oryzae In Vitro

“…The first group is cytochrome P450, a battery of cytochrome P450 genes were upregulated, included MGG_04345, MGG_04911, MGG_12496, MGG_05215, MGG_08947, and MGG_07593. It has been reported that P450-mediated detoxification is one of the most critical mechanisms in fungi and insect, and many P450 genes were upregulated when treated with fungicide, insecticide, and other chemicals [ 50 , 51 , 52 , 53 , 54 , 55 ]. The intracellular redox balance of fungi is critical for signal transduction and development, especially, when fungi are faced with stress.…”