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

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

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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 AFB1 to 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 AFB1 metabolism 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 AFBi to AFBO could be increased by upregulation of CYP1A1 and CYP2A6 expression,which was trans-activated owing to the upregu-lation 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 AFB1 to AFBO in chicken liver,which could provide novel targets for the remediation of aflatoxicosis in chicks.

aflatoxin B1CYP1A1CYP2A6SP1AP-1transcriptional activation

Jiang Deng、Jia-Cheng Yang、Yue Feng、Ze-Jing Xu、Kamil Ku?a、Meng Liu、Lv-Hui Sun

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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

Department of Chemistry,Faculty of Science,University of Hradec Kralove,Hradec Kralove 50003,Czech Republic

Chinese Natural Science Foundation ProjectsChinese Natural Science Foundation ProjectsChinese Natural Science Foundation ProjectsNational Key Research and Development Program of ChinaFundamental Research Funds for the Central UniversitiesTopnotch Young Talent Supporting Program to LHS,a gift from Beijing Deyuanshun Biotechnology Co.,Ltd

3177263632072775322729152023YFD13010032662023DKPY002

2024

10.1007/s11427-023-2512-6

中国科学:生命科学(英文版)
中国科学院

中国科学:生命科学(英文版)

CSTPCD
影响因子：0.806
ISSN：1674-7305
年,卷(期)：2024.67(7)