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.

• Keywords
• AP-1, CYP1A1, CYP2A6, SP1, aflatoxin B1, transcriptional activation,
• MeSH
• Aflatoxin B1 * metabolism   MeSH
• Transcriptional Activation MeSH
• Cytochrome P-450 CYP1A1 * genetics   metabolism   MeSH
• Cytochrome P-450 CYP2A6 * metabolism   genetics   MeSH
• Liver * metabolism   MeSH
• Chickens metabolism   MeSH
• Promoter Regions, Genetic MeSH
• Transcription Factor AP-1 * metabolism   genetics   MeSH
• Sp1 Transcription Factor * metabolism   genetics   MeSH
• Animals MeSH
• Check Tag
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Aflatoxin B1 * MeSH
• Cytochrome P-450 CYP1A1 * MeSH
• Cytochrome P-450 CYP2A6 * MeSH
• Transcription Factor AP-1 * MeSH
• Sp1 Transcription Factor * MeSH