Contribution of multidrug and toxin extrusion protein 1 (MATE1) to renal secretion of trimethylamine-N-oxide (TMAO).
Sci Rep
; 8(1): 6659, 2018 04 27.
Article
em En
| MEDLINE
| ID: mdl-29704007
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Oxidantes
/
Secreções Corporais
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Proteínas de Transporte de Cátions Orgânicos
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Metilaminas
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Sci Rep
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Alemanha