title: The involvement of cytochrome P450 monooxygenases in methanol elimination in Drosophila melanogaster larvae.
abstract: Methanol is one of the most common short-chain alcohols in fermenting fruits, the natural food of the fruit fly, Drosophila melanogaster. The larvae cope continuously with methanol at various concentrations in order to survive and develop. In the present article, we found toxicities of dietary methanol and formaldehyde were enhanced by piperonyl butoxide, but not by 3-amino-1, 2, 4-triazole, 4-methylpyrazole, diethylmeleate, and triphenyl phosphate, when assessing by the combination index method. These results reveal that cytochrome P450 monooxygenases (CYPs), rather than catalases, alcohol dehydrogenases, glutathione S-transferases, and esterases, participate in methanol metabolism. Moreover, methanol exposure dramatically increased CYP activity. The ratios of the CYP activities in treated larvae to those in control reached, respectively, up to 3.0-, 3.9-, and 2.7-fold, at methanol concentrations of 22.6, 27.9, and 34.5 mg/g diet. In addition, methanol exposure greatly up-regulated the mRNA expression level of five Cyp genes, which were Cyp304a1, Cyp9f2, Cyp28a5, Cyp4d2, and Cyp4e2. Their resulting proteins were suggested as the candidate enzymes for methanol metabolism in D. melanogaster larvae.
authors.affiliation: Education Ministry Key Laboratory of Integrated Management of Crop Diseases and Pests, College of Plant Protection, Nanjing Agricultural University, Nanjing, China.
authors.forename: Shu-Ping
authors.initials: SP
authors.lastname: Wang
authors.forename: Gui-Ling
authors.initials: GL
authors.lastname: He
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: D000818:Animals; D000840:Anisoles; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000201:enzymology* / Q000235:genetics; D004336:Drug Antagonism; D004357:Drug Synergism; D004791:Enzyme Inhibitors; D005557:Formaldehyde / Q000378:metabolism* / Q000633:toxicity; D005786:Gene Expression Regulation / Q000187:drug effects; D007814:Larva / Q000201:enzymology; D007928:Lethal Dose 50; D000432:Methanol / Q000378:metabolism* / Q000633:toxicity; D010882:Piperonyl Butoxide
chemical_list: D000840:Anisoles; D004791:Enzyme Inhibitors; D005557:Formaldehyde; D003577:Cytochrome P-450 Enzyme System; C005306:4-nitroanisole; D010882:Piperonyl Butoxide; D000432:Methanol