AP-1 and SP1 trans-activate the expression of hepatic CYP1A1 and CYP2A6 in the bioactivation of AFB1 in chicken  

作　　者：Jiang Deng Jia-Cheng Yang Yue Feng Ze-Jing Xu Kamil Kuča Meng Liu Lv-Hui Sun 

机构地区：[1]State Key Laboratory of Agricultural Microbiology,Hubei Hongshan Laboratory,Frontiers Science Center for Animal Breeding and Sustainable Production,College of Animal Sciences and Technology,Huazhong Agricultural University,Wuhan 430070,China [2]Department of Chemistry,Faculty of Science,University of Hradec Kralove,Hradec Kralove 50003,Czech Republic

出　　处：《Science China(Life Sciences)》2024年第7期1468-1478,共11页中国科学（生命科学英文版）

基　　金：partly supported by the Chinese Natural Science Foundation Projects(31772636,32072775,32272915);the National Key Research and Development Program of China(2023YFD1301003);the Fundamental Research Funds for the Central Universities(2662023DKPY002);the Top-notch Young Talent Supporting Program to LHS,a gift from Beijing Deyuanshun Biotechnology Co.,Ltd。

摘　　要：Dietary exposure to aflatoxin B1(AFB1)is harmful to the health and performance of domestic animals.The hepatic cytochrome P450s(CYPs),CYP1A1 and CYP2A6,are the primary enzymes responsible for the bioactivation of AFB1to the highly toxic exo-AFB1-8,9-epoxide(AFBO)in chicks.However,the transcriptional regulation mechanism of these CYP genes in the liver of chicks in AFB1metabolism remains unknown.Dual-luciferase reporter assay,bioinformatics and site-directed mutation results indicated that specificity protein 1(SP1)and activator protein-1(AP-1)motifs were located in the core region-1,063/-948,-606/-541 of the CYP1A1 promoter as well as-636/-595,-503/-462,-147/-1 of the CYP2A6 promoter.Furthermore,overexpression and decoy oligodeoxynucleotide technologies demonstrated that SP1 and AP-1 were pivotal transcriptional activators regulating the promoter activity of CYP1A1 and CYP2A6.Moreover,bioactivation of AFB1to AFBO could be increased by upregulation of CYP1A1 and CYP2A6 expression,which was trans-activated owing to the upregulation of AP-1,rather than SP1,stimulated by AFB1-induced reactive oxygen species.Additionally,nano-selenium could reduce ROS,downregulate AP-1 expression and then decrease the expression of CYP1A1 and CYP2A6,thus alleviating the toxicity of AFB1.In conclusion,AP-1 and SP1 played important roles in the transactivation of CYP1A1 and CYP2A6 expression and further bioactivated AFB1to AFBO in chicken liver,which could provide novel targets for the remediation of aflatoxicosis in chicks.

关 键 词：aflatoxin B1 CYP1A1 CYP2A6 SP1 AP-1 transcriptional activation 

分 类 号：S831[农业科学—畜牧学]