Bisphenol A Inhibits the Transporter Function of the Blood-Brain Barrier by Directly Interacting with the ABC Transporter Breast Cancer Resistance Protein (BCRP)

Engdahl, Elin, van Schijndel, Maarten DM, Voulgaris, Dimitrios, Di Criscio, Michela, Ramsbottom, Kerry A ORCID: 0000-0002-7432-9293, Rigden, Daniel J ORCID: 0000-0002-7565-8937, Herland, Anna and Ruegg, Joelle (2021) Bisphenol A Inhibits the Transporter Function of the Blood-Brain Barrier by Directly Interacting with the ABC Transporter Breast Cancer Resistance Protein (BCRP). INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 22 (11). 5534-.

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Official URL: http://dx.doi.org/10.3390/ijms22115534

Abstract

The breast cancer resistance protein (BCRP) is an important efflux transporter in the blood-brain barrier (BBB), protecting the brain from a wide range of substances. In this study, we investigated if BCRP function is affected by bisphenol A (BPA), a high production volume chemical used in common consumer products, as well as by bisphenol F (BPF) and bisphenol S (BPS), which are used to substitute BPA. We employed a transwell-based in vitro cell model of iPSC-derived brain microvascular endothelial cells, where BCRP function was assessed by measuring the intracellular accumulation of its substrate Hoechst 33342. Additionally, we used in silico modelling to predict if the bisphenols could directly interact with BCRP. Our results showed that BPA significantly inhibits the transport function of BCRP. Additionally, BPA was predicted to bind to the cavity that is targeted by known BCRP inhibitors. Taken together, our findings demonstrate that BPA inhibits BCRP function in vitro, probably by direct interaction with the transporter. This effect might contribute to BPA's known impact on neurodevelopment.

Item Type:	Article
Uncontrolled Keywords:	bisphenols, BPA, BPF, BPS, blood-brain barrier, BBB, BCRP, ABCG2, breast cancer resistance protein
Divisions:	Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User:	Symplectic Admin
Date Deposited:	12 Jul 2021 09:50
Last Modified:	18 Jan 2023 21:36
DOI:	10.3390/ijms22115534
Open Access URL:	https://www.mdpi.com/1422-0067/22/11/5534
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3129741