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家蝇中细胞色素P450lpr的成虫特异性表达与诱导

Adult specific expression and induction of cytochrome P450lpr in house flies.

作者信息

Scott J G, Sridhar P, Liu N

机构信息

Department of Entomology, Cornell University, Ithaca, New York 14853-0999, USA.

出版信息

Arch Insect Biochem Physiol. 1996;31(3):313-23. doi: 10.1002/(SICI)1520-6327(1996)31:3<313::AID-ARCH6>3.0.CO;2-Y.

DOI:10.1002/(SICI)1520-6327(1996)31:3<313::AID-ARCH6>3.0.CO;2-Y
PMID:8742827
Abstract

Cytochrome P450lpr is a xenobiotic metabolizing P450 that is found in house flies (Musca domestica). To better understand the regulation of cytochrome P450lpr, the effects of 21 potential monooxygenase inducers were examined for their ability to induce total cytochromes P450 and cytochrome P450lpr levels in adult flies. Six compounds caused induction of total cytochromes P450 per mg protein in adult susceptible (CS) house flies: ethanol (1.6-fold), phenobarbital in food (1.5-fold) or water (1.5-fold), naphthalene (1.3-fold), DDT (1.3-fold), xanthotoxin (1.4-fold), and alpha-pinene (1.2-fold). Six compounds were found to be inducers of cytochrome P450lpr: piperonyl butoxide in food (1.9-fold), phenobarbital in food (1.4-fold) and water (3.4-fold), clofibrate (1.3-fold), xanthotoxin (1.3-fold), methohexital (1.3-fold), and isosafrole (1.3-fold). Comparison of our results with house fly P450 6A1 indicates that there are specific inducers for each of these individual P450s as well as compounds that induce both P450s. Total P450s were inducible by PB in CS house fly larvae, but not in LPR larvae. Immunoblotting revealed no detectable P450lpr in control or PB-treated larvae in either strain. Thus, although total P450s are inducible in the susceptible strain larvae, P450lpr does not appear to be normally present or inducible with PB in larvae of either strain. Northern blots of phenobarbital (in water) treated CS flies indicated that there was a 4.2-fold increase in the P450lpr (i.e., CYP6D1) mRNA levels over the untreated flies. In the multiresistant LPR strain there was no apparent induction of CYP6D1 mRNA by phenobarbital. Following phenobarbital induction, the level of CYP6D1 mRNA in the CS strain was about half of the level in the LPR strain.

摘要

细胞色素P450lpr是一种存在于家蝇(Musca domestica)体内的参与异生物质代谢的P450。为了更好地了解细胞色素P450lpr的调控机制,研究人员检测了21种潜在的单加氧酶诱导剂对成年家蝇体内总细胞色素P450和细胞色素P450lpr水平的诱导能力。六种化合物可诱导成年敏感(CS)家蝇每毫克蛋白质中的总细胞色素P450水平升高:乙醇(1.6倍)、食物中的苯巴比妥(1.5倍)或水中的苯巴比妥(1.5倍)、萘(1.3倍)、滴滴涕(1.3倍)、花椒毒素(1.4倍)和α-蒎烯(1.2倍)。发现六种化合物可诱导细胞色素P450lpr:食物中的胡椒基丁醚(1.9倍)、食物中的苯巴比妥(1.4倍)和水中的苯巴比妥(3.4倍)、氯贝丁酯(1.3倍)、花椒毒素(1.3倍)、美索比妥(1.3倍)和异黄樟素(1.3倍)。将我们的结果与家蝇P450 6A1进行比较表明,这些单个P450各有其特定的诱导剂,也有能同时诱导两种P450的化合物。在CS家蝇幼虫中,苯巴比妥可诱导总P450水平升高,但在LPR幼虫中则不能。免疫印迹法显示,在两种品系的对照或经苯巴比妥处理的幼虫中均未检测到P450lpr。因此,尽管在敏感品系幼虫中总P450可被诱导,但在两种品系的幼虫中,P450lpr似乎通常不存在,也不能被苯巴比妥诱导。对经苯巴比妥(水中)处理的CS家蝇进行Northern印迹分析表明,与未处理的家蝇相比,P450lpr(即CYP6D1)mRNA水平增加了4.2倍。在多抗性LPR品系中,苯巴比妥对CYP6D1 mRNA没有明显的诱导作用。苯巴比妥诱导后,CS品系中CYP6D1 mRNA的水平约为LPR品系中水平的一半。

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