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

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Abstract

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 AFB1 to AFBO could be increased by upregulation of CYP1A1 and CYP2A6 expression, which was trans-activated owing to the upregulalion 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.

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The data that support the findings of this study are available from the corresponding author on reasonable request.

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Acknowledgement

This work was 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) and the Top-notch Young Talent Supporting Program to LHS, a gift from Bei**g Deyuanshun Biotechnology Co., Ltd.

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  1. Contributed equally to this work

Authors and Affiliations

  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

    Jiang Deng, Jia-Cheng Yang, Yue Feng, Ze-**g Xu, Meng Liu & Lv-Hui Sun

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

    Kamil Kuča

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  1. Jiang Deng
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  2. Jia-Cheng Yang
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  3. Yue Feng
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  6. Meng Liu
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  7. Lv-Hui Sun
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Correspondence to Meng Liu or Lv-Hui Sun.

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Deng, J., Yang, JC., Feng, Y. et al. AP-1 and SP1 trans-activate the expression of hepatic CYP1A1 and CYP2A6 in the bioactivation of AFB1 in chicken. Sci. China Life Sci. (2024). https://doi.org/10.1007/s11427-023-2512-6

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  • DOI: https://doi.org/10.1007/s11427-023-2512-6

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