Staffordshire University logo
STORE - Staffordshire Online Repository

A Systems Biology Approach Reveals the Endocrine Disrupting Potential of Aflatoxin B1

Verga, Jacopo U., Padovano, Costanzo, da Silveira, Willian A., Hazard, E. Starr, Nugent, Anne P., Elliott, Christopher T., Carnevali, Oliana, Galeazzi, Roberta and Hardiman, Gary (2023) A Systems Biology Approach Reveals the Endocrine Disrupting Potential of Aflatoxin B1. Exposure and Health, 16 (2). pp. 321-340. ISSN 2451-9766

s12403-023-00557-w.pdf - Publisher's typeset copy
Available under License Creative Commons Attribution 4.0 International (CC BY 4.0) .

Download (3MB) | Preview

Abstract or description

Aflatoxin B1 (AFB1) a mycotoxin produced by Aspergillus flavus and A. parasiticus is a potent carcinogen and causative agent of hepatocellular carcinoma (HCC). It is a food contaminant which presents a major risk to human health. AFB1 contamination poses a significant economic burden, as 25% of the world's food crops need to be destroyed annually. The mechanism of action (MOA) of aflatoxins remains to be fully elucidated. Recent findings suggest that AFB1 mediated endocrine disruption may occur in the population of regions with high contamination, even without evidence of direct dietary intake.

An integrative systems biology approach was undertaken to decipher the estrogenic component of the mechanism of action (MOA) of AFB1.

Molecular Docking and Molecular dynamics simulations were performed to examine the binding affinity of AFB1 and its metabolite aflatoxin Q1 (AFQ1) with the Estrogen Receptors (ERs). Differential gene expression (DGE), gene ontology (GO) and pathway analyses were carried out on hepatic transcriptomic data generated from in vivo AFB1 exposures. In parallel exposures to the synthetic estrogen ethinylestradiol (EE2) were examined for overlapping effects. Finally, protein–protein interaction (PPI) network analysis assessed the involvement of estrogen responsive targets (ERTs) associated with aflatoxin exposure.

The free energies of binding affinity and estimated equilibrium dissociation constants (KD) demonstrated that AFB1 and AFQ1 can interact with the ERα and ERβ. DGE and GO analyses highlighted overlap in the responses between AFB1 and EE2 treatments with the activation of key processes involved in estrogenic signaling. PPI network analyses after AFBI exposure revealed a dynamic response to AFB1 treatments with the solid involvement of ERTs in regulatory networks.

This study revealed molecular interactions between aflatoxins (AFB1, AFQ1) and ERs in addition to overlap in differentially expressed genes and biological processes following AFB1 and EE2 exposures. The estrogenic components at the core of the PPI networks suggest that ER-mediated signaling pathways are a major component in the MOA of aflatoxins.

Item Type: Article
Uncontrolled Keywords: Afatoxin B1 (AFB1) · Mechanism of action (MOA) · Ethinylestradiol (EE2) · Protein–protein interaction (PPI) network analysis · Estrogen receptors · ERα and Erβ · Estrogen responsive targets (ERTs)
Faculty: School of Life Sciences and Education > Biological and Biomedical Sciences
Depositing User: Willian DA SILVEIRA
Date Deposited: 22 Apr 2024 12:28
Last Modified: 22 Apr 2024 12:28

Actions (login required)

View Item View Item

DisabledGo Staffordshire University is a recognised   Investor in People. Sustain Staffs
Legal | Freedom of Information | Site Map | Job Vacancies
Staffordshire University, College Road, Stoke-on-Trent, Staffordshire ST4 2DE t: +44 (0)1782 294000