代谢
背景:尼腾吡胺是经济上重要的新烟碱类杀虫剂的一个成员。尼腾吡胺在体内的代谢尚不清楚,但是细胞色素P450活性是害虫对新烟碱类杀虫剂产生抗性的主要机制,P450s可以代谢其他新烟碱类杀虫剂,包括吡虫啉。结果:在这里,我们使用了GAL4-UAS靶向表达系统来指导RNA干扰(RNAi)针对细胞色素P450的氧化还原伙伴,以中断果蝇特定组织中的P450功能。对消化组织中避免驱避剂(dare)缺陷的线粒体氧化还原伙伴进行RNAi减少了尼腾吡胺的死亡率,这表明尼腾吡胺代谢的一个激活步骤是由线粒体P450执行的。对在消化组织中表达的线粒体细胞色素P450 Cyp12a5进行RNAi得到了相同的表型,而且Cyp12a5的转基因过表达增加了尼腾吡胺的敏感性。结论:这些结果表明,线粒体P450 CYP12A5在体内对尼腾吡胺的代谢导致了比原化合物毒性更高的产物的形成。
BACKGROUND: Nitenpyram is a member of the economically important neonicotinoid class of insecticides. The in vivo metabolism of nitenpyram is not well characterized, but cytochrome P450 activity is the major mechanism of resistance to neonicotinoids identified in insect pests, and P450s metabolize other neonicotinoids including imidacloprid. RESULTS: Here, we used the GAL4-UAS targeted expression system to direct RNA interference (RNAi) against the cytochrome P450 redox partners to interrupt P450 functions in specific tissues in Drosophila melanogaster. RNAi of the mitochondrial redox partner defective in the avoidance of repellents (dare) in the digestive tissues reduced nitenpyram mortality, suggesting an activation step in the metabolism of nitenpyram carried out by a mitochondrial P450. RNAi of the mitochondrial cytochrome P450 Cyp12a5, which is expressed in the digestive tissues, resulted in the same phenotype, and transgenic overexpression of Cyp12a5 increased nitenpyram sensitivity. CONCLUSION: These results suggest that in vivo metabolism of nitenpyram by the mitochondrial P450 CYP12A5 results in the formation of a product with higher toxicity than the parent compound.
来源:Hazardous Substances Data Bank (HSDB)