FOXO acts as a positive regulator of CncC and deltamethrin tolerance in the red flour beetle, Tribolium castaneum

Abstract

BACKGROUND Both forkhead box O (FOXO) and nuclear factor erythroid‐derived 2‐like‐2 (Nrf2) are key transcription factors related to stress responses. Whereas limited studies in mammals and Caenorhabditis elegans have revealed the interaction between FoxO/DAF‐16 and Nrf2/SKN‐1, the role of FOXO in metabolic detoxification and regulation of the Nrf2–Keap1 signaling pathway are poorly understood in insects. RESULTS Using Tribolium castaneum as a model organism, we found that RNA interference‐mediated knockdown of FOXO enhanced deltamethrin‐induced lethality by affecting the messenger RNA (mRNA) levels of CYP6BQ cluster genes. We further demonstrated that injection of dsFOXO into the beetle larvae decreased expression of CncC and KEAP1 at both the mRNA and protein level. Notably, dual‐luciferase and electrophoretic mobility shift assays both confirmed direct regulation of CncC by FOXO, whereas Keap1 was directly regulated by CncC. CONCLUSION FOXO can directly regulate the expression of CncC and indirectly regulate the expression of Keap1 through CncC. The data provide insights into the regulatory mechanisms of the Nrf2–Keap1 signaling pathway in insects.

Two Point Mutations in CYP4CE1 Promoter Contributed to the Differential Regulation of CYP4CE1 Expression by FoxO between Susceptible and Nitenpyram-Resistant Nilaparvata lugens

“…20 It was verified in T. castaneum that FoxO directly regulates the expression of CncC and CYP6BQ cluster genes, leading to enhanced deltamethrininduced lethality. 21 FoxO signaling pathway was also reported to be involved in the regulation of GST genes, which responded to acetamiprid stress in Bombyx mori. 22 In N. lugens, FoxO is a critical downstream effector of the insulin/ insulin-like peptide signaling.…”

Two point mutations in CYP4CE1 promoter contributed to the differential regulation of CYP4CE1 expression by FoxO between susceptible and nitenpyram resistant Nilaparvata lugens

“…FoxO is also a key factor related to stress responses, including oxidative stress and xenobiotic stress (de Keizer et al, 2011). It was veri ed in T. castaneum that FoxO directly regulate the expression of CncC and CYP6BQ cluster genes, leading to the enhanced deltamethrin-induced lethality (Xu et al, 2022). FoxO signaling pathway was also reported to be involved in the regulation of GST genes, which responded to acetamiprid stress in Bombyx mori (Wang et al, 2020).…”