Contribution of multidrug and toxin extrusion protein 1 (MATE1) to renal secretion of trimethylamine-N-oxide (TMAO)

Journal article


Publication Details

Author(s): Geßner A, König J, Fromm M
Journal: Scientific Reports
Publication year: 2018
Volume: 8
Journal issue: 1
ISSN: 2045-2322


Abstract

Trimethylamine-N-oxide (TMAO) gained considerable attention because of its role as a cardiovascular risk biomarker. Organic cation transporter 2 (OCT2) mediates TMAO uptake into renal proximal tubular cells. Here we investigated the potential role of multidrug and toxin extrusion protein 1 (MATE1) for translocation of TMAO across the luminal membrane of proximal tubular cells. HEK293 cells stably expressing OCT2 (HEK-OCT2) or MATE1 (HEK-MATE1) were used for uptake studies. Transcellular transport of TMAO was investigated using monolayers of MDCK control cells (MDCK-Co) as well as single- (MDCK-OCT2, MDCK-MATE1) and double-transfected cells (MDCK-OCT2-MATE1). In line with previous studies, HEK-OCT2 cells revealed a 2.4-fold uptake of TMAO compared to control cells (p < 0.001), whereas no significant uptake was observed in HEK-MATE1. In monolayers of MDCK cells, polarised TMAO transcellular transport was not significantly different between MDCK-Co and MDCK-OCT2 cells, but significantly increased in MDCK-MATE1 (p < 0.05) and MDCK-OCT2-MATE1 cells (p < 0.001). The OCT/MATE inhibitor trimethoprim abolished TMAO translocation in MDCK-OCT2-MATE1 cells (p < 0.05). The present data suggest that MATE1 contributes to renal elimination of TMAO. For selected MATE substrates, such as TMAO, uptake studies using non-polarised MATE-expressing cells can reveal false negative results compared to studies using polarised monolayers.


FAU Authors / FAU Editors

Fromm, Martin Prof. Dr.
Lehrstuhl für Klinische Pharmakologie und Klinische Toxikologie
Geßner, Arne Dr.
Lehrstuhl für Klinische Pharmakologie und Klinische Toxikologie
König, Jörg Prof. Dr.
Lehrstuhl für Klinische Pharmakologie und Klinische Toxikologie


How to cite

APA:
Geßner, A., König, J., & Fromm, M. (2018). Contribution of multidrug and toxin extrusion protein 1 (MATE1) to renal secretion of trimethylamine-N-oxide (TMAO). Scientific Reports, 8(1). https://dx.doi.org/10.1038/s41598-018-25139-8

MLA:
Geßner, Arne, Jörg König, and Martin Fromm. "Contribution of multidrug and toxin extrusion protein 1 (MATE1) to renal secretion of trimethylamine-N-oxide (TMAO)." Scientific Reports 8.1 (2018).

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Last updated on 2019-28-02 at 06:13