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细胞色素 P450 单加氧酶在黑腹果蝇幼虫甲醇消除中的作用。

The involvement of cytochrome P450 monooxygenases in methanol elimination in Drosophila melanogaster larvae.

机构信息

Education Ministry Key Laboratory of Integrated Management of Crop Diseases and Pests, College of Plant Protection, Nanjing Agricultural University, Nanjing, China.

出版信息

Arch Insect Biochem Physiol. 2012 Apr;79(4-5):264-75. doi: 10.1002/arch.21021. Epub 2012 Apr 16.

DOI:10.1002/arch.21021
PMID:22508581
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.

摘要

甲醇是发酵水果中最常见的短链醇之一,也是果蝇的天然食物。为了生存和发育,幼虫会持续接触不同浓度的甲醇。在本文中,我们发现经联合指数法评估,胡椒基丁醚增强了膳食甲醇和甲醛的毒性,但 3-氨基-1,2,4-三唑、4-甲基吡唑、二乙甲酯和三苯基膦则没有。这些结果表明细胞色素 P450 单加氧酶(CYPs)而不是过氧化氢酶、醇脱氢酶、谷胱甘肽 S-转移酶和酯酶参与了甲醇代谢。此外,甲醇暴露显著增加了 CYP 活性。在 22.6、27.9 和 34.5 mg/g 饮食浓度下,处理幼虫中的 CYP 活性与对照相比分别增加了 3.0 倍、3.9 倍和 2.7 倍。此外,甲醇暴露极大地上调了五个 Cyp 基因的 mRNA 表达水平,它们是 Cyp304a1、Cyp9f2、Cyp28a5、Cyp4d2 和 Cyp4e2。这些蛋白被认为是果蝇幼虫甲醇代谢的候选酶。

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