Carrier-Mediated and Energy-Dependent Uptake and Efflux of Deoxynivalenol in Mammalian Cells

Abstract Deoxynivalenol (DON) is one of the most abundant mycotoxins and exerts many adverse effects on humans and animals. To date, the transporting mechanism of DON in mammalian cells remains unclear. In this study, the parallel artificial membrane permeability assay (PAMPA), Transwell models and...

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Autores principales:	Xiaoming Li, Peiqiang Mu, Jikai Wen, Yiqun Deng
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e211e07b97e54cc58c1f1eb5ede95418
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spelling	oai:doaj.org-article:e211e07b97e54cc58c1f1eb5ede954182021-12-02T16:06:31ZCarrier-Mediated and Energy-Dependent Uptake and Efflux of Deoxynivalenol in Mammalian Cells10.1038/s41598-017-06199-82045-2322https://doaj.org/article/e211e07b97e54cc58c1f1eb5ede954182017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-06199-8https://doaj.org/toc/2045-2322Abstract Deoxynivalenol (DON) is one of the most abundant mycotoxins and exerts many adverse effects on humans and animals. To date, the transporting mechanism of DON in mammalian cells remains unclear. In this study, the parallel artificial membrane permeability assay (PAMPA), Transwell models and metabolic inhibitors were used to determine the possible transporting mechanisms of DON in Caco-2, MDCK and HepG2 cells. PAMPA and Transwell models showed reduced passive transport and increased intestinal absorption, indicating a carrier-mediated transporting mechanism. Furthermore, higher unidirectional transport of DON was observed in the basolateral-to-apical direction than in the apical-to-basolateral direction, indicating the existence of efflux proteins. Interestingly, DON was accumulated in the nucleus, and no DON was detected in mitochondria, indicating that the nucleus may be the main target organelle of DON. Moreover, the use of various transporter inhibitors in different cells shows that organic anion transporters, organic cation transporters, and organic anion-transporting polypeptides participate in DON uptake, and P-glycoprotein is the major efflux protein. Importantly, DON uptake is strongly inhibited by metabolic inhibitors and is highly dependent on temperature. In summary, carrier-mediated and energy-dependent uptake and efflux mechanisms for DON in mammalian cells are reported, aiding in improving our understanding of its toxicological mechanisms.Xiaoming LiPeiqiang MuJikai WenYiqun DengNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Xiaoming Li Peiqiang Mu Jikai Wen Yiqun Deng Carrier-Mediated and Energy-Dependent Uptake and Efflux of Deoxynivalenol in Mammalian Cells
description	Abstract Deoxynivalenol (DON) is one of the most abundant mycotoxins and exerts many adverse effects on humans and animals. To date, the transporting mechanism of DON in mammalian cells remains unclear. In this study, the parallel artificial membrane permeability assay (PAMPA), Transwell models and metabolic inhibitors were used to determine the possible transporting mechanisms of DON in Caco-2, MDCK and HepG2 cells. PAMPA and Transwell models showed reduced passive transport and increased intestinal absorption, indicating a carrier-mediated transporting mechanism. Furthermore, higher unidirectional transport of DON was observed in the basolateral-to-apical direction than in the apical-to-basolateral direction, indicating the existence of efflux proteins. Interestingly, DON was accumulated in the nucleus, and no DON was detected in mitochondria, indicating that the nucleus may be the main target organelle of DON. Moreover, the use of various transporter inhibitors in different cells shows that organic anion transporters, organic cation transporters, and organic anion-transporting polypeptides participate in DON uptake, and P-glycoprotein is the major efflux protein. Importantly, DON uptake is strongly inhibited by metabolic inhibitors and is highly dependent on temperature. In summary, carrier-mediated and energy-dependent uptake and efflux mechanisms for DON in mammalian cells are reported, aiding in improving our understanding of its toxicological mechanisms.
format	article
author	Xiaoming Li Peiqiang Mu Jikai Wen Yiqun Deng
author_facet	Xiaoming Li Peiqiang Mu Jikai Wen Yiqun Deng
author_sort	Xiaoming Li
title	Carrier-Mediated and Energy-Dependent Uptake and Efflux of Deoxynivalenol in Mammalian Cells
title_short	Carrier-Mediated and Energy-Dependent Uptake and Efflux of Deoxynivalenol in Mammalian Cells
title_full	Carrier-Mediated and Energy-Dependent Uptake and Efflux of Deoxynivalenol in Mammalian Cells
title_fullStr	Carrier-Mediated and Energy-Dependent Uptake and Efflux of Deoxynivalenol in Mammalian Cells
title_full_unstemmed	Carrier-Mediated and Energy-Dependent Uptake and Efflux of Deoxynivalenol in Mammalian Cells
title_sort	carrier-mediated and energy-dependent uptake and efflux of deoxynivalenol in mammalian cells
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/e211e07b97e54cc58c1f1eb5ede95418
work_keys_str_mv	AT xiaomingli carriermediatedandenergydependentuptakeandeffluxofdeoxynivalenolinmammaliancells AT peiqiangmu carriermediatedandenergydependentuptakeandeffluxofdeoxynivalenolinmammaliancells AT jikaiwen carriermediatedandenergydependentuptakeandeffluxofdeoxynivalenolinmammaliancells AT yiqundeng carriermediatedandenergydependentuptakeandeffluxofdeoxynivalenolinmammaliancells
_version_	1718384995463069696

Carrier-Mediated and Energy-Dependent Uptake and Efflux of Deoxynivalenol in Mammalian Cells

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