地塞米松对从江香猪细胞色素氧化酶P450 3A29 mRNA表达的影响
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摘要
从江香猪是全国稀有的微型猪种,其细胞色素氧化酶P450基因纯合度较高,遗传稳定,具备开发药物代谢动物模型的良好基础。本研究旨在应用实时荧光定量方法研究从江香猪细胞色素氧化酶P450 3A29 mRNA的组织分布及地塞米松对其表达的影响,并比较与人细胞色素氧化酶P450 3A4的相似性。结果表明,从江香猪细胞色素氧化酶P450 3A29 m RNA的组织分布特征及地塞米松对其诱导作用总体上与人体相似,从江香猪可用于人细胞色素氧化酶P450 3A4的诱导研究。
Congjiang Xiang-pig is a rare species of miniature pig in China. It has a good basis for animal model of drug metabolism because of its highly homozygous and stable heredity of P450 genes. The aim of this study is to analyze the tissue distribution and the effect of dexamethasone on the expression of Congjiang Xiang-pigs CYP3 A29 mRNA by real-time RT-PCR, and compare the similarity with that of human CYP3 A4. The results showed that the characters of tissue distribution and the induction effect of dexamethasone on the expression of CYP3 A29 mRNA in Congjiang Xiang-pigs were similar to those of human beings, and Congjiang Xiang-pig could be used in the induction study of human CYP3 A4.
Congjiang Xiang-pig is a rare species of miniature pig in China. It has a good basis for animal model of drug metabolism because of its highly homozygous and stable heredity of P450 genes. The aim of this study is to analyze the tissue distribution and the effect of dexamethasone on the expression of Congjiang Xiang-pigs CYP3 A29 mRNA by real-time RT-PCR, and compare the similarity with that of human CYP3 A4. The results showed that the characters of tissue distribution and the induction effect of dexamethasone on the expression of CYP3 A29 mRNA in Congjiang Xiang-pigs were similar to those of human beings, and Congjiang Xiang-pig could be used in the induction study of human CYP3 A4.
引文
Bode G.,Clausing P.,Gervais F.,Loegsted J.,Luft J.,Nogues V.,and Sims J.,2010,Steering group of the RETHINK project.The utility of minipig as an animal model in regulatory toxicology,Journal of Pharmacological and Toxicological Methods,62(3):196-220
Bogaards J.J.,Bertrand M.,Jackson P.,Oudshoorn M.J.,Weaver R.J.,van Bladeren P.J.,and Walther B.,2000,Determining the best animal model for human cytochrome P450 activities:a comparison of mouse,rat,rabbit,dog,micropig,monkey and man,Xenobiotica,30(12):1131-1152
Cantiello M.,Giantin M.,Carletti M.,Lopparelli R.M.,Capolongo F.,Lasserre F.,Bollo E.,Nebbia C.,Martin P.G.,Pineau T.,and Dacasto M.,2009,Effects of dexamethasone,administered for growth promoting purposes,upon the hepatic cytochrome P450 3A expression in the veal calf,Biochemical Pharmacology,77(3):451-463
Down M.J.,Arkle S.,and Mills J.J.,2007,Regulation and induction of CYP3A11,CYP3A13 and CYP3A25 in C57BL/6Jmouse liver,Archives of Biochemistry and Biophysics,457(1):105-110
Giantin M.,Zancanella V.,Lopparelli R.M.,Granato A.,Carletti M.,Vilei M.T.,Muraca M.,Baratto C.,and Dacasto M.,2012,Effects of time culture and prototypical cytochrome P450 3A(CYP3A)inducers on CYP2B22,CYP2C,CYP3A and nuclear receptor(NR)m RNAs in long-term cryopreserved pig hepatocytes(CPHs),Drug Metabolism and Pharmacokinetics,27(5):495-505
Graham M.J.,and Lake B.G.,2008,Induction of drug metabolism:species differences and toxicological relevance,Toxicology,254(3):184-191
Jones B.C.,Rollison H.,Johansson S.,Kanebratt K.P.,Lambert C.,Vishwanathan K.,and Andersson T.B.,2017,Managing the risk of CYP3A induction in drug development:a strategic approach,Drug Metabolism and Disposition,45(1):35-41
Kato M.,Chiba K.,Horikawa M.,and Sugiyama Y.,2005,The quantitative prediction of in vivo enzyme-induction caused by drug exposure from in vitro information on human hepatocytes,Drug Metabolism and Pharmacokinetics,20(4):236-243
Kobayashi K.,Abe C.,Endo M.,Kazuki Y.,Oshimura M.,and Chiba K.,2017,Gender difference of hepatic and intestinal CYP3A4 in CYP3A-humanized mice generated by a human chromosome-engineering technique,Drug Metabolism Letters,11(1):60-67
Lee S.J.,and Buhler D.R.,2003,Cloning,tissue distribution,and functional studies of a new cytochrome P450 3A subfamily member,CYP3A45,from rainbow trout(Oncorhynchus mykiss)intestinal ceca,Archives of Biochemistry and Biophysics,412(1):77-89
Li J.,Chen R.,Yao Q.Y.,Liu S.J.,Tian X.Y.,Hao C.Y.,Lu W.,and Zhou T.Y.,2018,Time-dependent pharmacokinetics of dexamethasone and its efficacy in human breast cancer xenograft mice:a semi-mechanism-based pharmacokinetic/pharmacodynamic model,Acta Pharmacologica Sinica,39:472-481
LI J.,Liu Y.,Zhang J.W.,Wei H.,and Ying L.,2006,Characterization of hepatic drug-metabolizing activities of Bama miniature pigs(Sus Scrofa Dodmestica):comparison with human enzyme analogs,Comparative Medicine,56(4):269-273
Martínez-Pérez E.F.,Hernández-Terán F.,and Serrano-Gallardo L.B.,2017,In vivo effect of ruta chalepensis extract on hepatic cytochrome 3A1 in rats,African Journal of Traditional,Complementary and Alternative Medicines,14(4):62-68
MatéM.L.,Ballent M.,Larsen K.,Lifschitz A.,Lanusse C.,and Virkel G.,2015,Gene expression and enzyme function of two cytochrome P450 3A isoenzymes in rat and cattle precision cut liver slices,Xenobiotica,45(7):563-570
MatéM.L.,Lifschitz A.,Sallovitz J.,Ballent M.,Muscher A.S.,Wilkens M.R.,Schr?der B.,Lanusse C.,and Virkel G.,2012,Cytochrome P450 3A expression and function in liver and intestinal mucosa from dexamethasone-treated sheep,Journal of Veterinary Pharmacology and Therapeutics,35(4):319-328
Matsunaga T.,Maruyama M.,Matsubara T.,Nagata K.,Yamazoe Y.,and Ohmori S.,2012,Mechanisms of CYP3A induction by glucocorticoids in human fetal liver cells,Drug Metabo-lism and Pharmacokinetics,27(6):653-657
Mealey K.L.,Jabbes M.,Spencer E.,and Akey J.M.,2008,Differential expression of CYP3A12 and CYP3A26 m RNAs in canine liver and intestine,Xenobiotica,38(10):1305-1312
Messina A.,Nannelli A.,Fiorio R.,Longo V.,and Gervasi P.G.,2009,Expression and inducibility of CYP1A1,1A2,1B1 byβ-naphthoflavone and CYP2B22,3A22,3A29 3A46 by rifampicin in the respiratory and olfactory mucosa of pig,Toxicology,260(1-3):47-52
Nakagawa T.,Fowler S.,Takanashi K.,Youdim K.,Yamauchi T.,Kawashima K.,Sato-Nakai M.,Yu L.,and Ishigai M.,2018,In vitro metabolism of alectinib,a novel potent ALK inhibitor,in human:contribution of CYP3A enzymes,Xenobiotica,48(6):546-554
Nishimura M.,Koeda A.,Suganuma Y.,Suzuki E.,Shimizu T.,Nakayama M.,Satoh T.,Narimatsu S.,and Naito S.,2007,Comparison of inducibility of CYP1A and CYP3A m RNAs by prototypical inducers in primary cultures of human,cynomolgus monkey,and rat hepatocytes,Drug Metabolism and Pharmacokinetics,22(3):178-186
Nishimura M.,Yaguti H.,Yoshitsugu H.,Naito S.,and Satoh T.,2003,Tissue distribution of m RNA expression of human cytochorme P450 isoforms assessed by high-sensitivity real-time reverse transcription PCR,Yakugaku Zasshi,123(5):369-375
Nishimuta H.,Nakagawa T.,Nomura N.,and Yabuki M.,2013,Species differences in hepatic and intestinal metabolic activities for 43 human cytochrome P450 substrates between humans and rats or dogs,Xenobiotica,43(11):948-955
Pham C.,Nagar S.,and Korzekwa K.,2017,Numerical analysis of time dependent inhibition kinetics:comparison between rat liver microsomes and rat hepatocyte data for mechanistic model fitting,Xenobiotica,2017:1-28
Puccinelli E.,Gervasi P.G.,La Marca M.,Beffy P.,and Longo V.,2010,Expression and inducibility by phenobarbital of CYP2C33,CYP2C42,CYP2C49,CYP2B22 and CYP3As in porcine liver,kidney,small intestine,and nasal tissues,Xenobiotica,40(8):525-535
Shang H.,Yang J.,Liu Y.,and Wei H.,2009,Tissue distribution of CYP3A29 m RNA expression in Bama miniature pig by quantitative reverse transcriptase-polymerase chain reaction(RT-PCR),Xenobiotica,39(6):423-429
Souèek P.,Zuber R.,AnzenbacherováE.,Anzenbacher P.,and Guengerich F.P.,2001,Minipig cytochrome P450 3A,2Aand 2C enzymes have similar properties to human analogs,BMC Pharmacology,1:11
Stamou M.,Wu X.,Kania-Korwel I.,Lehmler H.J.,and Lein P.J.,2014,Cytochrome p450 m RNA expression in the rodent brain:species-,sex-,and region-dependent differences,Drug Metabolism and Disposition,42(2):239-244
Van Peer E.,De Bock L.,Boussery K.,Van Bocxlaer J.,Casteleyn C.,Van Ginneken C.,and Van Cruchten S.,2015,Agerelated differences in CYP3A abundance and activity in the liver of the G?ttingen minipig,Basic&Clinical Pharmacology&Toxicology,117(5):350-357
Wang X.W.,and Zeng S.,2009,Heterogenous expression and activity analysis of human cytochrome P450 3A4 mutants CYP3A4.3,CYP3A4.4,CYP3A4.5 and CYP3A4.18,Zhongguo Yaolixue Yu Dulixue Zazhi(Chinese Journal of Pharmacology and Toxicology),23(6):456-463(王晓雯,曾苏,2009,人细胞色素P450 3A4突变体CYP3A4.3,CYP3A4.4,CY-P3A4.5和CYP3A4.18重组酶的异源表达与活性,中国药理学与毒理学杂志,23(6):456-463)
Yang J.D.,Ren Q.,and Wu S.R.,2016a,Population genetics of single nucleotide polymorphisms of CYP2A19 gene in Congjiang Xiang-pig,Nanfang Nongye Xuebao(Journal of Southern Agriculture),47(7):1209-1215(杨家大,任琼,吴声榕,2016a,从江香猪CYP2A19基因单核苷酸多态性的群体遗传学分析,南方农业学报,47(7):1209-1215)
Yang J.D.,Ren Q.,and Wu S.R.,2016b,Distribution of single nucleotide polymorphisms of CYP2E1 gene in Congjiang Xiang-pigs,Jiyinzuxue Yu Yingyong Shengwuxue(Genomics and Applied Biology),35(10):2676-2685(杨家大,任琼,吴声榕,2016b,CYP2E1基因单核苷酸多态性在从江香猪中的分布,基因组学与应用生物学,35(10):2676-2685)
Yang J.D.,Ren Q.,and Wu S.R.,2016c,Polymorphisms of four exons in Congjiang Xiang-pig gene CYP1A2,Guizhou Nongye Kexue(Guizhou Agricultural Sciences),44(10):84-90(杨家大,任琼,吴声榕,2016c,从江香猪CYP1A2基因4个外显子的多态性,贵州农业科学,44(10):84-90)
Yao M.,Dai M.,Liu Z.,Huang L.,Chen D.,Wang Y.,Peng D.,Wang X.,Liu Z.,and Yuan Z.,2011,Comparison of the substrate kinetics of pig CYP3A29 with pig liver microsomes and human CYP3A4,Bioscience Reports,31(3):211-220
Bogaards J.J.,Bertrand M.,Jackson P.,Oudshoorn M.J.,Weaver R.J.,van Bladeren P.J.,and Walther B.,2000,Determining the best animal model for human cytochrome P450 activities:a comparison of mouse,rat,rabbit,dog,micropig,monkey and man,Xenobiotica,30(12):1131-1152
Cantiello M.,Giantin M.,Carletti M.,Lopparelli R.M.,Capolongo F.,Lasserre F.,Bollo E.,Nebbia C.,Martin P.G.,Pineau T.,and Dacasto M.,2009,Effects of dexamethasone,administered for growth promoting purposes,upon the hepatic cytochrome P450 3A expression in the veal calf,Biochemical Pharmacology,77(3):451-463
Down M.J.,Arkle S.,and Mills J.J.,2007,Regulation and induction of CYP3A11,CYP3A13 and CYP3A25 in C57BL/6Jmouse liver,Archives of Biochemistry and Biophysics,457(1):105-110
Giantin M.,Zancanella V.,Lopparelli R.M.,Granato A.,Carletti M.,Vilei M.T.,Muraca M.,Baratto C.,and Dacasto M.,2012,Effects of time culture and prototypical cytochrome P450 3A(CYP3A)inducers on CYP2B22,CYP2C,CYP3A and nuclear receptor(NR)m RNAs in long-term cryopreserved pig hepatocytes(CPHs),Drug Metabolism and Pharmacokinetics,27(5):495-505
Graham M.J.,and Lake B.G.,2008,Induction of drug metabolism:species differences and toxicological relevance,Toxicology,254(3):184-191
Jones B.C.,Rollison H.,Johansson S.,Kanebratt K.P.,Lambert C.,Vishwanathan K.,and Andersson T.B.,2017,Managing the risk of CYP3A induction in drug development:a strategic approach,Drug Metabolism and Disposition,45(1):35-41
Kato M.,Chiba K.,Horikawa M.,and Sugiyama Y.,2005,The quantitative prediction of in vivo enzyme-induction caused by drug exposure from in vitro information on human hepatocytes,Drug Metabolism and Pharmacokinetics,20(4):236-243
Kobayashi K.,Abe C.,Endo M.,Kazuki Y.,Oshimura M.,and Chiba K.,2017,Gender difference of hepatic and intestinal CYP3A4 in CYP3A-humanized mice generated by a human chromosome-engineering technique,Drug Metabolism Letters,11(1):60-67
Lee S.J.,and Buhler D.R.,2003,Cloning,tissue distribution,and functional studies of a new cytochrome P450 3A subfamily member,CYP3A45,from rainbow trout(Oncorhynchus mykiss)intestinal ceca,Archives of Biochemistry and Biophysics,412(1):77-89
Li J.,Chen R.,Yao Q.Y.,Liu S.J.,Tian X.Y.,Hao C.Y.,Lu W.,and Zhou T.Y.,2018,Time-dependent pharmacokinetics of dexamethasone and its efficacy in human breast cancer xenograft mice:a semi-mechanism-based pharmacokinetic/pharmacodynamic model,Acta Pharmacologica Sinica,39:472-481
LI J.,Liu Y.,Zhang J.W.,Wei H.,and Ying L.,2006,Characterization of hepatic drug-metabolizing activities of Bama miniature pigs(Sus Scrofa Dodmestica):comparison with human enzyme analogs,Comparative Medicine,56(4):269-273
Martínez-Pérez E.F.,Hernández-Terán F.,and Serrano-Gallardo L.B.,2017,In vivo effect of ruta chalepensis extract on hepatic cytochrome 3A1 in rats,African Journal of Traditional,Complementary and Alternative Medicines,14(4):62-68
MatéM.L.,Ballent M.,Larsen K.,Lifschitz A.,Lanusse C.,and Virkel G.,2015,Gene expression and enzyme function of two cytochrome P450 3A isoenzymes in rat and cattle precision cut liver slices,Xenobiotica,45(7):563-570
MatéM.L.,Lifschitz A.,Sallovitz J.,Ballent M.,Muscher A.S.,Wilkens M.R.,Schr?der B.,Lanusse C.,and Virkel G.,2012,Cytochrome P450 3A expression and function in liver and intestinal mucosa from dexamethasone-treated sheep,Journal of Veterinary Pharmacology and Therapeutics,35(4):319-328
Matsunaga T.,Maruyama M.,Matsubara T.,Nagata K.,Yamazoe Y.,and Ohmori S.,2012,Mechanisms of CYP3A induction by glucocorticoids in human fetal liver cells,Drug Metabo-lism and Pharmacokinetics,27(6):653-657
Mealey K.L.,Jabbes M.,Spencer E.,and Akey J.M.,2008,Differential expression of CYP3A12 and CYP3A26 m RNAs in canine liver and intestine,Xenobiotica,38(10):1305-1312
Messina A.,Nannelli A.,Fiorio R.,Longo V.,and Gervasi P.G.,2009,Expression and inducibility of CYP1A1,1A2,1B1 byβ-naphthoflavone and CYP2B22,3A22,3A29 3A46 by rifampicin in the respiratory and olfactory mucosa of pig,Toxicology,260(1-3):47-52
Nakagawa T.,Fowler S.,Takanashi K.,Youdim K.,Yamauchi T.,Kawashima K.,Sato-Nakai M.,Yu L.,and Ishigai M.,2018,In vitro metabolism of alectinib,a novel potent ALK inhibitor,in human:contribution of CYP3A enzymes,Xenobiotica,48(6):546-554
Nishimura M.,Koeda A.,Suganuma Y.,Suzuki E.,Shimizu T.,Nakayama M.,Satoh T.,Narimatsu S.,and Naito S.,2007,Comparison of inducibility of CYP1A and CYP3A m RNAs by prototypical inducers in primary cultures of human,cynomolgus monkey,and rat hepatocytes,Drug Metabolism and Pharmacokinetics,22(3):178-186
Nishimura M.,Yaguti H.,Yoshitsugu H.,Naito S.,and Satoh T.,2003,Tissue distribution of m RNA expression of human cytochorme P450 isoforms assessed by high-sensitivity real-time reverse transcription PCR,Yakugaku Zasshi,123(5):369-375
Nishimuta H.,Nakagawa T.,Nomura N.,and Yabuki M.,2013,Species differences in hepatic and intestinal metabolic activities for 43 human cytochrome P450 substrates between humans and rats or dogs,Xenobiotica,43(11):948-955
Pham C.,Nagar S.,and Korzekwa K.,2017,Numerical analysis of time dependent inhibition kinetics:comparison between rat liver microsomes and rat hepatocyte data for mechanistic model fitting,Xenobiotica,2017:1-28
Puccinelli E.,Gervasi P.G.,La Marca M.,Beffy P.,and Longo V.,2010,Expression and inducibility by phenobarbital of CYP2C33,CYP2C42,CYP2C49,CYP2B22 and CYP3As in porcine liver,kidney,small intestine,and nasal tissues,Xenobiotica,40(8):525-535
Shang H.,Yang J.,Liu Y.,and Wei H.,2009,Tissue distribution of CYP3A29 m RNA expression in Bama miniature pig by quantitative reverse transcriptase-polymerase chain reaction(RT-PCR),Xenobiotica,39(6):423-429
Souèek P.,Zuber R.,AnzenbacherováE.,Anzenbacher P.,and Guengerich F.P.,2001,Minipig cytochrome P450 3A,2Aand 2C enzymes have similar properties to human analogs,BMC Pharmacology,1:11
Stamou M.,Wu X.,Kania-Korwel I.,Lehmler H.J.,and Lein P.J.,2014,Cytochrome p450 m RNA expression in the rodent brain:species-,sex-,and region-dependent differences,Drug Metabolism and Disposition,42(2):239-244
Van Peer E.,De Bock L.,Boussery K.,Van Bocxlaer J.,Casteleyn C.,Van Ginneken C.,and Van Cruchten S.,2015,Agerelated differences in CYP3A abundance and activity in the liver of the G?ttingen minipig,Basic&Clinical Pharmacology&Toxicology,117(5):350-357
Wang X.W.,and Zeng S.,2009,Heterogenous expression and activity analysis of human cytochrome P450 3A4 mutants CYP3A4.3,CYP3A4.4,CYP3A4.5 and CYP3A4.18,Zhongguo Yaolixue Yu Dulixue Zazhi(Chinese Journal of Pharmacology and Toxicology),23(6):456-463(王晓雯,曾苏,2009,人细胞色素P450 3A4突变体CYP3A4.3,CYP3A4.4,CY-P3A4.5和CYP3A4.18重组酶的异源表达与活性,中国药理学与毒理学杂志,23(6):456-463)
Yang J.D.,Ren Q.,and Wu S.R.,2016a,Population genetics of single nucleotide polymorphisms of CYP2A19 gene in Congjiang Xiang-pig,Nanfang Nongye Xuebao(Journal of Southern Agriculture),47(7):1209-1215(杨家大,任琼,吴声榕,2016a,从江香猪CYP2A19基因单核苷酸多态性的群体遗传学分析,南方农业学报,47(7):1209-1215)
Yang J.D.,Ren Q.,and Wu S.R.,2016b,Distribution of single nucleotide polymorphisms of CYP2E1 gene in Congjiang Xiang-pigs,Jiyinzuxue Yu Yingyong Shengwuxue(Genomics and Applied Biology),35(10):2676-2685(杨家大,任琼,吴声榕,2016b,CYP2E1基因单核苷酸多态性在从江香猪中的分布,基因组学与应用生物学,35(10):2676-2685)
Yang J.D.,Ren Q.,and Wu S.R.,2016c,Polymorphisms of four exons in Congjiang Xiang-pig gene CYP1A2,Guizhou Nongye Kexue(Guizhou Agricultural Sciences),44(10):84-90(杨家大,任琼,吴声榕,2016c,从江香猪CYP1A2基因4个外显子的多态性,贵州农业科学,44(10):84-90)
Yao M.,Dai M.,Liu Z.,Huang L.,Chen D.,Wang Y.,Peng D.,Wang X.,Liu Z.,and Yuan Z.,2011,Comparison of the substrate kinetics of pig CYP3A29 with pig liver microsomes and human CYP3A4,Bioscience Reports,31(3):211-220
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