title: The involvement of several enzymes in methanol detoxification in Drosophila melanogaster adults.
abstract: Methanol is among the most common short-chain alcohols in fermenting fruits, the natural food and oviposition sites of the fruit fly Drosophila melanogaster. Our previous results showed that cytochrome P450 monooxygenases (CYPs) were associated with methanol detoxification in the larvae. Catalases, alcohol dehydrogenases (ADHs), esterases (ESTs) and glutathione S-transferases (GSTs) were specifically inhibited by 3-amino-1,2,4-triazole (3-AT), 4-methylpyrazole (4-MP), triphenyl phosphate (TPP) and diethylmeleate (DEM), respectively. CYPs were inhibited by piperonyl butoxide (PBO) and 1-aminobenzotriazole (1-ABT). In the present paper, the involvements of these enzymes in methanol metabolism were investigated in female and male adults by determining the combination indices of methanol and their corresponding inhibitors. When PBO, 1-ABT, 3-AT, 4-MP and TPP were individually mixed with methanol, they exhibited significant synergism to the mortality of the adults after 72h of dietary exposure. In contrast, the DEM and methanol mixture showed additive effects. Moreover, methanol exposure dramatically increased CYP activity and up-regulated mRNA expression levels of several Cyp genes. Bioassays using different strains revealed that the variation in ADH activity and RNAi-mediated knockdown of α-Est7 significantly changed LC50 values for methanol. These results suggest that CYPs, catalases, ADHs and ESTs are partially responsible for methanol elimination in adults. It seems that there are some differences in methanol metabolism between larvae and adults, but not between female and male adults.
authors.affiliation: Education Ministry Key Laboratory of Integrated Management of Crop Diseases and Pests, College of Plant Protection, Nanjing Agricultural University, Nanjing 210095, China.
authors.forename: Shu-Ping
authors.initials: SP
authors.lastname: Wang
authors.forename: Xing-Xing
authors.initials: XX
authors.lastname: Hu
authors.forename: Qing-Wei
authors.initials: QW
authors.lastname: Meng
authors.forename: Shahid Arain
authors.initials: SA
authors.lastname: Muhammad
authors.forename: Rui-Rui
authors.initials: RR
authors.lastname: Chen
authors.forename: Fei
authors.initials: F
authors.lastname: Li
authors.forename: Guo-Qing
authors.initials: GQ
authors.lastname: Li
mesh_terms: D000426:Alcohol Dehydrogenase / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D002374:Catalase / Q000037:antagonists & inhibitors / Q000378:metabolism; D004331:Drosophila melanogaster / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000008:administration & dosage*; D004950:Esterases / Q000037:antagonists & inhibitors / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D005982:Glutathione Transferase / Q000037:antagonists & inhibitors / Q000378:metabolism; D050216:Metabolic Detoxication, Phase I / Q000235:genetics*; D000432:Methanol / Q000378:metabolism* / Q000633:toxicity; D006899:Mixed Function Oxygenases / Q000037:antagonists & inhibitors / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects
chemical_list: D004791:Enzyme Inhibitors; D012333:RNA, Messenger; D006899:Mixed Function Oxygenases; D000426:Alcohol Dehydrogenase; D002374:Catalase; D005982:Glutathione Transferase; D004950:Esterases; D000432:Methanol
keywords: Alcohol dehydrogenase; Catalase; Cytochrome P450 monooxygenase; Esterase; Methanol metabolism