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Article

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

1
Environmental Toxicology, Department of Organismal Biology, Uppsala University, 75236 Uppsala, Sweden
2
Division of Micro and Nanosystems, Department of Intelligent Systems, KTH Royal Institute of Technology, 11428 Stockholm, Sweden
3
AIMES, Department of Neuroscience, Karolinska Institute, 17177 Solna, Sweden
4
Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool L69 3BX, UK
5
Computational Biology Facility, Technology Directorate, University of Liverpool, Liverpool L69 3BX, UK
*
Author to whom correspondence should be addressed.
Academic Editor: Lester Drewes
Int. J. Mol. Sci. 2021, 22(11), 5534; https://doi.org/10.3390/ijms22115534
Received: 6 May 2021 / Revised: 16 May 2021 / Accepted: 19 May 2021 / Published: 24 May 2021
(This article belongs to the Collection Feature Papers in Molecular Toxicology)
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. View Full-Text
Keywords: bisphenols; BPA; BPF; BPS; blood-brain barrier; BBB; BCRP; ABCG2; breast cancer resistance protein bisphenols; BPA; BPF; BPS; blood-brain barrier; BBB; BCRP; ABCG2; breast cancer resistance protein
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MDPI and ACS Style

Engdahl, E.; van Schijndel, M.D.M.; Voulgaris, D.; Di Criscio, M.; Ramsbottom, K.A.; Rigden, D.J.; Herland, A.; Rüegg, J. Bisphenol A Inhibits the Transporter Function of the Blood-Brain Barrier by Directly Interacting with the ABC Transporter Breast Cancer Resistance Protein (BCRP). Int. J. Mol. Sci. 2021, 22, 5534. https://doi.org/10.3390/ijms22115534

AMA Style

Engdahl E, van Schijndel MDM, Voulgaris D, Di Criscio M, Ramsbottom KA, Rigden DJ, Herland A, Rüegg J. 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. 2021; 22(11):5534. https://doi.org/10.3390/ijms22115534

Chicago/Turabian Style

Engdahl, Elin, Maarten D.M. van Schijndel, Dimitrios Voulgaris, Michela Di Criscio, Kerry A. Ramsbottom, Daniel J. Rigden, Anna Herland, and Joëlle Rüegg. 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, no. 11: 5534. https://doi.org/10.3390/ijms22115534

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