Rogalski Felipe, Tsuda Manabu, Takeo Satomi, Asano Tsunaki, Sakai Takaomi, Aigaki Toshiro
Department of Biological Sciences, Tokyo Metropolitan University, 1-1 Minami-Osawa, Hachioji, Tokyo, 192-0397, Japan.
Department of Liberal Arts and Human Development, Kanagawa University of Human Services, 1-10-1, Heiseicho, Yokosuka-shi, Kanagawa, 238-8522, Japan.
Biochem Biophys Res Commun. 2025 Feb 8;748:151313. doi: 10.1016/j.bbrc.2025.151313. Epub 2025 Jan 9.
Epoxide hydrolases (EHs) play pivotal roles in detoxification, catabolism, and signaling by converting epoxides into diols and have been implicated in several diseases, such as cancers and diabetes. EH homologs in insects are designated as Juvenile hormone epoxide hydrolases (JHEHs) due to their catalytic activity toward Juvenile hormone (JH). However, the biological function of JHEHs has been controversial in the fruit fly Drosophila melanogaster. In this study, we generated and characterized flies deficient in Jheh1 and Jheh2 genes. We found that Jheh1/2 deficiency caused a developmental delay and enhanced the growth retardation effects of caffeine and paraquat. Additionally, we observed that the deficiency reduced tolerance to cold stress. These results indicate that JHEHs are required for growth promotion and stress tolerance. Metabolomic and transcriptomic analyses revealed that Jheh1/2 deficiency impaired glucose metabolism and downregulated genes involved in glycolysis and the TCA cycle. Furthermore, transgenic overexpression of Jheh1 increased glycolytic metabolites and restored the Jheh1/2 deficiency-associated phenotype. These results demonstrate that JHEHs play a crucial role in glucose metabolism in Drosophila, providing a valuable model to study the mechanisms underlying the function of EHs in energy metabolism.
环氧水解酶（EHs）通过将环氧化物转化为二醇，在解毒、分解代谢和信号传导中发挥关键作用，并与多种疾病有关，如癌症和糖尿病。昆虫中的EH同源物因其对保幼激素（JH）的催化活性而被命名为保幼激素环氧水解酶（JHEHs）。然而，JHEHs在果蝇中的生物学功能一直存在争议。在本研究中，我们构建并鉴定了Jheh1和Jheh2基因缺失的果蝇。我们发现Jheh1/2基因缺失导致发育延迟，并增强了咖啡因和百草枯的生长迟缓效应。此外，我们观察到这种缺失降低了对冷应激的耐受性。这些结果表明，JHEHs是促进生长和应激耐受所必需的。代谢组学和转录组学分析表明，Jheh1/2基因缺失损害了葡萄糖代谢，并下调了参与糖酵解和三羧酸循环的基因。此外，Jheh1的转基因过表达增加了糖酵解代谢物，并恢复了与Jheh1/2基因缺失相关的表型。这些结果表明，JHEHs在果蝇的葡萄糖代谢中起关键作用，为研究EHs在能量代谢中功能的潜在机制提供了有价值的模型。
