| RRC ID |
83710
|
| 著者 |
Rogalski F, Tsuda M, Takeo S, Asano T, Sakai T, Aigaki T.
|
| タイトル |
Epoxide hydrolases JHEH1 and JHEH2 deficiency impairs glucose metabolism in Drosophila.
|
| ジャーナル |
Biochem Biophys Res Commun
|
| Abstract |
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.
|
| 巻・号 |
748
|
| ページ |
151313
|
| 公開日 |
2025-2-8
|
| DOI |
10.1016/j.bbrc.2025.151313
|
| PII |
S0006-291X(25)00027-0
|
| PMID |
39809137
|
| MeSH |
Animals
Animals, Genetically Modified
Caffeine / pharmacology
Drosophila Proteins* / deficiency
Drosophila Proteins* / genetics
Drosophila Proteins* / metabolism
Drosophila melanogaster* / enzymology
Drosophila melanogaster* / genetics
Drosophila melanogaster* / growth & development
Drosophila melanogaster* / metabolism
Epoxide Hydrolases* / deficiency
Epoxide Hydrolases* / genetics
Epoxide Hydrolases* / metabolism
Glucose* / metabolism
Glycolysis
|
| IF |
2.985
|
| リソース情報 |
| ショウジョウバエ |
TBX-0001 |
