Mechanistic insight into human androgen receptor-mediated endocrine disrupting potential of cyclic depsipeptide mycotoxin, beauvericin, and influencing environmental factors for its biosynthesis in Fusarium oxysporum KFCC 11363P on rice cereal

• Published in: Ecotoxicology and environmental safety Vol. 274; p. 116227
• Main Authors: Jeong, Da-Hyun, Jung, Da-Woon, You, Chaemin, Lee, Hee-Seok
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 01.04.2024; Elsevier
• Subjects: Androgen receptor; Antagonist; Beauvericin; Depsipeptides - toxicity; Edible Grain - chemistry; Endocrine Disruptors - chemistry; Endocrine Disruptors - toxicity; Fusarium - metabolism; Humans; Influencing environmental factor; Mycotoxins - toxicity; Oryza - chemistry; Receptors, Androgen - drug effects; Receptors, Androgen - metabolism; Response surface methodology; Influencing environmental factor; AR; Androgen receptor; Antagonist; Response surface methodology; Beauvericin; TA; RSM; BEA; BA
• ISSN: 0147-6513; 1090-2414
• DOI: 10.1016/j.ecoenv.2024.116227

In current study, Fusarium mycotoxin, beauvericin (BEA), has endocrine disrupting potential through suppressing the exogenous androgen receptor (AR)-mediated transcriptional activation. BEA was classified as an AR antagonist, with IC30 and IC50 values indicating that it suppressed AR dimerization in the cytosol. BEA suppress the translocation of cytosolic activated ARs to the nucleus via exogenous androgens. Furthermore, we investigated the impact of environmental conditions for BEA production on rice cereal using response surface methodology. The environmental factors affecting the production of BEA, namely temperature, initial moisture content, and growth time were optimized at 20.28 °C, 42.79 % (w/w), and 17.31 days, respectively. To the best of our knowledge, this is the first report showing that BEA has endocrine disrupting potential through suppressing translocation of cytosolic ARs to nucleus, and temperature, initial moisture content, and growth time are important influencing environmental factors for its biosynthesis in Fusarium strains on cereal. [Display omitted] •Beauvericin could have endocrine disrupting effects.•Beauvericin is determined to be an AR antagonist in transcriptional activation assay.•Beauvericin suppressed the dimerization of AR in cytoplasm.•This suppressing cause to block the translocation of cytoplasmic AR proteins to nucleus.•Condition of influencing environmental factors were investigated using RSM.