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 

作者机构：State Key Laboratory of Agricultural MicrobiologyHubei Hongshan LaboratoryFrontiers Science Center for Animal Breeding and Sustainable ProductionCollege of Animal Sciences and TechnologyHuazhong Agricultural UniversityWuhan 430070China Department of ChemistryFaculty of ScienceUniversity of Hradec KraloveHradec Kralove 50003Czech Republic 

出 版 物：《Science China(Life Sciences)》 (中国科学（生命科学英文版）)

年 卷 期：2024年第67卷第7期

页      面：1468-1478页

核心收录：

学科分类：0710[理学-生物学] 0905[农学-畜牧学] 09[农学] 

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 

主　　题：aflatoxin B1 CYP1A1 CYP2A6 SP1 AP-1 transcriptional activation 

摘      要：Dietary exposure to aflatoxin B1(AFB1)is harmful to the health and performance of domestic *** 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 ***,the transcriptional regulation mechanism of these CYP genes in the liver of chicks in AFB1metabolism remains ***-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 ***,overexpression and decoy oligodeoxynucleotide technologies demonstrated that SP1 and AP-1 were pivotal transcriptional activators regulating the promoter activity of CYP1A1 and ***,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 ***,nano-selenium could reduce ROS,downregulate AP-1 expression and then decrease the expression of CYP1A1 and CYP2A6,thus alleviating the toxicity of *** 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.