细胞色素P450介导的果蝇抗药性研究进展
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摘要
细胞色素P450 (cytochrome P450, CYP450)超基因家族是由一些数量多而功能复杂的血红蛋白酶基因所组成,该代谢酶系作为一种几乎地球上所有需氧生物都存在的重要生存策略,可以调控多种内源物质及外源化合物的代谢,参与了众多重要的生命过程,代谢解毒作用是该酶系重要功能之一。细胞色素P450的代谢解毒作用受药物影响,机体通过改变基因表达量,实现增强代谢解毒,加快机体对于有害物质的代谢,从而使得机体对有害环境产生一定的适应性,进而使得机体产生耐药性或抗药性。本研究说明果蝇细胞色素P450介导的杀虫剂类药物代谢机制及代谢抗性的特点等方面的研究,对明确果蝇的抗药性机制研究具有参考意义。
Cytochrome P450(cytochrome P450, CYP450) supergene family is composed of a large number of hemoglobin enzymes with complex functions. As an important survival strategy for almost all aerobic organisms on the earth, the metabolic enzymes can regulate the metabolism of many endogenous substances and exogenous compounds and participate in many important life processes. Metabolic detoxification is one of the important functions of this enzyme system. The strength of metabolic detoxification of cytochrome P450 is affected by drugs.By changing gene expression, the organism can enhance metabolism and detoxification, accelerate the metabolism of harmful substances, so that the organism can adapt to harmful environment, and then make the organism produce drug tolerance or resistance. This study demonstrated that the studies on the metabolic mechanism of insecticides and the characteristics of metabolic resistance mediated by cytochrome P450 enzymes in Drosophila would be of reference significance to clarify the resistance mechanism of Drosophila.
Cytochrome P450(cytochrome P450, CYP450) supergene family is composed of a large number of hemoglobin enzymes with complex functions. As an important survival strategy for almost all aerobic organisms on the earth, the metabolic enzymes can regulate the metabolism of many endogenous substances and exogenous compounds and participate in many important life processes. Metabolic detoxification is one of the important functions of this enzyme system. The strength of metabolic detoxification of cytochrome P450 is affected by drugs.By changing gene expression, the organism can enhance metabolism and detoxification, accelerate the metabolism of harmful substances, so that the organism can adapt to harmful environment, and then make the organism produce drug tolerance or resistance. This study demonstrated that the studies on the metabolic mechanism of insecticides and the characteristics of metabolic resistance mediated by cytochrome P450 enzymes in Drosophila would be of reference significance to clarify the resistance mechanism of Drosophila.
引文
Am ichot M.,Ta rès S.,Brun-Barale A.,Arthaud L.,Bride J.M.,and BergéJ.B.,2004,Point mutations associated with insecticide resistance in the Drosophila cytochrome p450cyp6a2 enable DDT metabolism,Eur.J.Biochem.,271(7):1250-1257
Bhaskara S.,Chandrasekharan M.B.,and Ganguly R.,2008,Caffeine induction of Cyp6a2 and Cyp6a8 genes of Drosophila melanogaster is modulated by cAMP and D-JUN protein levels,Gene,415(1):49-59
Battlay P.,Schmidt J.M.,Fournier-Level A.,and Robin C.,2016,Genomic and transcriptomic associations identify a new insecticide resistance phenotype for the selective sweep at the Cyp6g1 locus of Drosophila melanogaster,G3 Genesgenetics,6(8):2573-2581
Bogwitz M.R.,Chung H.,Magoc L.,Rigby S.,Wong W.,O'Keefe M.,McKenzie J.A.,Batterham P.,and Daborn P.J.,2005,Cyp12a4 confers lufenuron resistance in a natural population of Drosophila melanogaster,Proc.Natl.Acad.Sci.USA,102(36):12807-12812
Catania F.,Kauer M.O.,Daborn P.J.,Yen J.L.,Ffrench-constant R.H.,and Schlotterer C.,2004,World-wide survey of an accord insertion and its association with DDT resistance in Drosophila melanogaster,Molecular Ecolo.,13(8):2491-2504
Chung H.,Bogwitz M.R.,Mccart C.,Andrianopoulos A.,Ffrenchconstant R.H.,Batterham P.,and Daborn P.J.,2007,Cis-regulatory elements in the accord retrotransposon result in tissue-specific expression of the Drosophila melanogaster insecticide resistance gene cyp6g1,Genetics,175(3):1071-1077
Daborn P.J.,Yen J.L.,Bogwitz M.R.,Goff G.L.,Feil E.,Jeffers S.,Tijet N.,Perry T.,Heckel D.,Batterham P.,Feyereisen R.,Wilson T.G.,and ffrench-Constant R.H.,2002,A single P450 allele associated with insecticide resistance in Drosophila,Science,297(5590):2253-2256
Daborn P.,Boundy S.,Yen J.,Pittendrigh B.,and ffrench-Constant R.,2001,DDT resistance in Drosophila correlates withCyp6g1 over-expression and confers cross-resistance to the neonicotinoid imidacloprid,Mol.Genet Genomics.,266(4):556-563
Denholm I.,Devine G.J.,and Williamson M.S.,2002,Insecticide resistance on the move,Science,297(5590):2222-2223
Denecke S.,Fusetto R.,Martelli F.,Giang A.,Battlay P.,Fournier-Level A.,O'Hair R.A.,and Batterham P.,2017,Multiple P450s and variation in neuronal genes underpins the response to the insecticide imidacloprid in a population of Drosophila melanogaster,Sci.Rep.,7(1):11338
Le Goff G.,Boundy S.,Daborn P.J.,Yen J.L.,Sofer L.,Lind R.,Sabourault C.,Madi-Ravazzi L.,and ffrench-Constant R.H.,2003,Microarray analysis of cytochrome p450 mediated insecticide resistance in Drosophila,Insect.Biochem.Mol.Biol.,33(7):701-708
Geerts R.,Zande L.V.D.,and Bijlsma R.,2004,Is DDT resistance in Drosophila melanogaster associated with increased expression of the Cytochrome P450 gene cyp6g1,Proceedings of the Section Experimental and Applied Entomology-Netherlands Entomological Society,15:71-74
Gellatly K.J.,Yoon K.S.,Doherty J.J.,Sun W.,Pittendrigh B.R.,and Clark J.M.,2015,Rnai validation of resistance genes and their interactions in the highly ddt-resistant 91-r,strain of Drosophila melanogaster,Pestic.Biochem.Physiol.,121:107-115
Huang W.,Carbone M.A.,Magwire M.M.,Peiffer J.A.,Lyman R.F.,Stone E.A.,Anholt R.R.H.,and Mackay T.F.C.,2015,Genetic basis of transcriptome diversity in Drosophila melanogaster,Proc.Natl.Acad.Sci.USA,112(44):6010-6019
Jouβen N.,Agnolet S.,Lorenz S.,Schone S.E.,Ellinger R.,Schneider B.,and Heckela D.G.,2012,Resistance of australian helicoverpa armigera to fenvalerate is due to the chimeric p450 enzyme Cyp337b3,Proc.Natl.Acad.Sci.USA,109(38):15206-15211
Kuruganti S.,Lam V.,Zhou X.G.,Bennett G.,Pittendrigh B.R.,and Ganguly R.,2007,High expression of cyp6g1,a cytochrome P450 gene,does not necessarily confer DDT resistance in Drosophila melanogaster,Gene,388(2):43-53
Pedra J.H.F.,Mcintyre L.M.,Scharf M.E.,and Pittendrigh B.R.,2004,Genome-wide transcription profile of field-and laboratory-selected dichlorodiphenyltrichloroethane(DDT)-resistant Drosophila,Proc.Natl.Acad.Sci.USA,101(18):7034
Peyser R.D.,Lanno S.M.,Shimshak S.J.,and Coolon J.D.,2017,Analysis of cytochrome p450 contribution to evolved plant toxin resistance in Drosophila sechellia,Insect.Mol.Biol.,26(6):715-720
Saner C.,Weibel B.,Wurgler F.E.,and Sengstag C.,2015,Metabolism of promutagens catalyzed by Drosophila melanogaster Cyp6a2 enzyme in saccharomyces cerevisiae,Environ.Mol.Mutagen.,27(1):46-58
Scott J.G.,and Kasai S.,2004,Evolutionary plasticity of monooxygenase-mediated resistance,Pestic.Biochem.Physiol.,78(3):171-178
Terhzaz S.,Cabrero P.,Brinzer R.A.,Halberg K.A.,Dow J.A.T.,and Davies S.,2015,A novel role of Drosophila cytochrome P450-4e3 in permethrin insecticide tolerance,Insect.Biochem.Mol.Biol.,67:38
Wan H.,Liu Y.,Li M.,Zhu S.Y.,Li X.C.,Pittendrigh B.R.,and Qiu X.H.,2014,Nrf2/maf-binding-site-containing functional cyp6a2,allele is associated with DDT resistance in Drosophila melanogaster,Pest Management Science,70(7):1048-1058
Wang S.P.,Hu X.X.,Meng Q.W.,Muhammad S.A.,Chen R.R.,Li F.,and Li G.Q.,2013,The involvement of several enzymes in methanol detoxification in Drosophila melanogaster adults,Comp.Biochem.Physiol.B Biochem.Mol.Biol.,166(1):7-14
Bhaskara S.,Chandrasekharan M.B.,and Ganguly R.,2008,Caffeine induction of Cyp6a2 and Cyp6a8 genes of Drosophila melanogaster is modulated by cAMP and D-JUN protein levels,Gene,415(1):49-59
Battlay P.,Schmidt J.M.,Fournier-Level A.,and Robin C.,2016,Genomic and transcriptomic associations identify a new insecticide resistance phenotype for the selective sweep at the Cyp6g1 locus of Drosophila melanogaster,G3 Genesgenetics,6(8):2573-2581
Bogwitz M.R.,Chung H.,Magoc L.,Rigby S.,Wong W.,O'Keefe M.,McKenzie J.A.,Batterham P.,and Daborn P.J.,2005,Cyp12a4 confers lufenuron resistance in a natural population of Drosophila melanogaster,Proc.Natl.Acad.Sci.USA,102(36):12807-12812
Catania F.,Kauer M.O.,Daborn P.J.,Yen J.L.,Ffrench-constant R.H.,and Schlotterer C.,2004,World-wide survey of an accord insertion and its association with DDT resistance in Drosophila melanogaster,Molecular Ecolo.,13(8):2491-2504
Chung H.,Bogwitz M.R.,Mccart C.,Andrianopoulos A.,Ffrenchconstant R.H.,Batterham P.,and Daborn P.J.,2007,Cis-regulatory elements in the accord retrotransposon result in tissue-specific expression of the Drosophila melanogaster insecticide resistance gene cyp6g1,Genetics,175(3):1071-1077
Daborn P.J.,Yen J.L.,Bogwitz M.R.,Goff G.L.,Feil E.,Jeffers S.,Tijet N.,Perry T.,Heckel D.,Batterham P.,Feyereisen R.,Wilson T.G.,and ffrench-Constant R.H.,2002,A single P450 allele associated with insecticide resistance in Drosophila,Science,297(5590):2253-2256
Daborn P.,Boundy S.,Yen J.,Pittendrigh B.,and ffrench-Constant R.,2001,DDT resistance in Drosophila correlates withCyp6g1 over-expression and confers cross-resistance to the neonicotinoid imidacloprid,Mol.Genet Genomics.,266(4):556-563
Denholm I.,Devine G.J.,and Williamson M.S.,2002,Insecticide resistance on the move,Science,297(5590):2222-2223
Denecke S.,Fusetto R.,Martelli F.,Giang A.,Battlay P.,Fournier-Level A.,O'Hair R.A.,and Batterham P.,2017,Multiple P450s and variation in neuronal genes underpins the response to the insecticide imidacloprid in a population of Drosophila melanogaster,Sci.Rep.,7(1):11338
Le Goff G.,Boundy S.,Daborn P.J.,Yen J.L.,Sofer L.,Lind R.,Sabourault C.,Madi-Ravazzi L.,and ffrench-Constant R.H.,2003,Microarray analysis of cytochrome p450 mediated insecticide resistance in Drosophila,Insect.Biochem.Mol.Biol.,33(7):701-708
Geerts R.,Zande L.V.D.,and Bijlsma R.,2004,Is DDT resistance in Drosophila melanogaster associated with increased expression of the Cytochrome P450 gene cyp6g1,Proceedings of the Section Experimental and Applied Entomology-Netherlands Entomological Society,15:71-74
Gellatly K.J.,Yoon K.S.,Doherty J.J.,Sun W.,Pittendrigh B.R.,and Clark J.M.,2015,Rnai validation of resistance genes and their interactions in the highly ddt-resistant 91-r,strain of Drosophila melanogaster,Pestic.Biochem.Physiol.,121:107-115
Huang W.,Carbone M.A.,Magwire M.M.,Peiffer J.A.,Lyman R.F.,Stone E.A.,Anholt R.R.H.,and Mackay T.F.C.,2015,Genetic basis of transcriptome diversity in Drosophila melanogaster,Proc.Natl.Acad.Sci.USA,112(44):6010-6019
Jouβen N.,Agnolet S.,Lorenz S.,Schone S.E.,Ellinger R.,Schneider B.,and Heckela D.G.,2012,Resistance of australian helicoverpa armigera to fenvalerate is due to the chimeric p450 enzyme Cyp337b3,Proc.Natl.Acad.Sci.USA,109(38):15206-15211
Kuruganti S.,Lam V.,Zhou X.G.,Bennett G.,Pittendrigh B.R.,and Ganguly R.,2007,High expression of cyp6g1,a cytochrome P450 gene,does not necessarily confer DDT resistance in Drosophila melanogaster,Gene,388(2):43-53
Pedra J.H.F.,Mcintyre L.M.,Scharf M.E.,and Pittendrigh B.R.,2004,Genome-wide transcription profile of field-and laboratory-selected dichlorodiphenyltrichloroethane(DDT)-resistant Drosophila,Proc.Natl.Acad.Sci.USA,101(18):7034
Peyser R.D.,Lanno S.M.,Shimshak S.J.,and Coolon J.D.,2017,Analysis of cytochrome p450 contribution to evolved plant toxin resistance in Drosophila sechellia,Insect.Mol.Biol.,26(6):715-720
Saner C.,Weibel B.,Wurgler F.E.,and Sengstag C.,2015,Metabolism of promutagens catalyzed by Drosophila melanogaster Cyp6a2 enzyme in saccharomyces cerevisiae,Environ.Mol.Mutagen.,27(1):46-58
Scott J.G.,and Kasai S.,2004,Evolutionary plasticity of monooxygenase-mediated resistance,Pestic.Biochem.Physiol.,78(3):171-178
Terhzaz S.,Cabrero P.,Brinzer R.A.,Halberg K.A.,Dow J.A.T.,and Davies S.,2015,A novel role of Drosophila cytochrome P450-4e3 in permethrin insecticide tolerance,Insect.Biochem.Mol.Biol.,67:38
Wan H.,Liu Y.,Li M.,Zhu S.Y.,Li X.C.,Pittendrigh B.R.,and Qiu X.H.,2014,Nrf2/maf-binding-site-containing functional cyp6a2,allele is associated with DDT resistance in Drosophila melanogaster,Pest Management Science,70(7):1048-1058
Wang S.P.,Hu X.X.,Meng Q.W.,Muhammad S.A.,Chen R.R.,Li F.,and Li G.Q.,2013,The involvement of several enzymes in methanol detoxification in Drosophila melanogaster adults,Comp.Biochem.Physiol.B Biochem.Mol.Biol.,166(1):7-14