Transport of N-acetyl-S-(1,2-dichlorovinyl)-L-cysteine, a Metabolite of Trichloroethylene, by Mouse Multidrug Resistance Associated Protein 2 (Mrp2)

Overview

Journal Toxicol Appl Pharmacol

Specialties Pharmacology
Toxicology

Date 2010 Jan 12

PMID 20060011

Citations 3

Authors

Kirill Tsirulnikov

Natalia Abuladze

Myong-Chul Koag

Debra Newman

Karoline Scholz

Galyna Bondar

Quansheng Zhu

Nuraly K Avliyakulov

Wolfgang Dekant

Kym Faull

Ira Kurtz

Alexander Pushkin

Affiliations

Soon will be listed here.

Abstract

N-acetyl-S-(1,2-dichlorovinyl)-l-cysteine (Ac-DCVC) and S-(1,2-dichlorovinyl)-l-cysteine (DCVC) are the glutathione conjugation pathway metabolites of a common industrial contaminant and potent nephrotoxicant trichloroethylene (TCE). Ac-DCVC and DCVC are accumulated in the renal proximal tubule where they may be secreted into the urine by an unknown apical transporter(s). In this study, we explored the hypothesis that the apical transport of Ac-DCVC and/or DCVC may be mediated by the multidrug resistance associated protein 2 (Mrp2, ABCC2), which is known to mediate proximal tubular apical ATP-dependent transport of glutathione and numerous xenobiotics and endogenous substances conjugated with glutathione. Transport experiments using membrane vesicles prepared from mouse proximal tubule derived cells expressing mouse Mrp2 utilizing ATPase assay and direct measurements of Ac-DCVC/DCVC using liquid chromatography/tandem mass-spectrometry (LC/MS/MS) demonstrated that mouse Mrp2 mediates ATP-dependent transport of Ac-DCVC. Expression of mouse Mrp2 antisense mRNA significantly inhibited the vectorial basolateral to apical transport of Ac-DCVC but not DCVC in mouse proximal tubule derived cells endogenously expressing mouse Mrp2. The results suggest that Mrp2 may be involved in the renal secretion of Ac-DCVC.

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