A multidisciplinary approach disclosing unexplored Aflatoxin B1 roles in severe impairment of vitamin D mechanisms of action

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Abstract

Aflatoxin B1 (AFB1), produced by fungi of the genus Aspergillus, is the most toxic and carcinogenic mycotoxin among the classes of aflatoxins. Previous research showed that AFB1 affects vitamin D receptor (VDR) expression. In the present study, integrated computational and experimental studies were carried out to investigate how AFB1 can interfere with Vitamin D signalling. A competitive antagonism of AFB1 toward RXRα and VDR was hypothesized by comparing the docked complex of AFB1/RXRα and AFB1/VDR ligand-binding domain (LBD) with the X-ray structures of RXRα and VDR bound to known ligands. Accordingly, we demonstrated that AFB1 can affect vitamin D-mediated transcriptional activation of VDR by impairing the formation of protein complexes containing both VDR-RXRα and RXRα/RAR and affecting the subcellular localization of VDR and RXRα. As a whole, our data indicate that AFB1 can interfere with different molecular pathways triggered by vitamin D with an antagonistic mechanism of action.

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Persico, M., Sessa, R., Cesaro, E., Dini, I., Costanzo, P., Ritieni, A., … Grosso, M. (2023). A multidisciplinary approach disclosing unexplored Aflatoxin B1 roles in severe impairment of vitamin D mechanisms of action. Cell Biology and Toxicology, 39(4), 1275–1295. https://doi.org/10.1007/s10565-022-09752-y

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