# Multidrug Resistance-Associated Proteins 3 and 5 Play a Role in the Hepatic Transport of Mercuric Conjugates of Glutathione

## TL;DR

This study shows that MRP3 and MRP5 transport mercury conjugated with glutathione in liver cells.

## Contribution

The study is the first to demonstrate that MRP3 and MRP5 can export mercury conjugates.

## Key findings

- GSH-Hg-GSH is a substrate for MRP3 and MRP5 transporters.
- Transport of GSH-Hg-GSH by MRP3 and MRP5 follows saturable kinetics.
- This is the first evidence that MRP3 and MRP5 can export mercury.

## Abstract

Multidrug resistance proteins (MRPs) are transporters for metabolic waste and xenobiotics and are known to export a wide range of substances from renal tubular cells. This study aimed to define and characterize the transport of mercuric conjugates of glutathione (GSH-Hg-GSH) in inside-out membrane vesicles containing MRP3 and MPR5. The functionality of the MRP3 and MRP5 vesicles was confirmed by measuring the uptake of [3H]-estradiol and 5-6-carboxy-2′,7′-dichloro-fluorescein (CDCF) over time (at 1, 5, 15, and 30 min). The uptake of GSH-Hg-GSH, containing radioactive mercury ([203Hg]), was measured in each set of membrane vesicles over time, and the findings suggest that GSH-Hg-GSH is a substrate of MRP3 and MRP5. The saturation kinetics were also analyzed by measuring the uptake of 10 µM GSH-[203Hg]-GSH in the presence of 25, 50, or 100 µM unlabeled GSH-Hg-GSH for 5 min at 37 °C. The transport of GSH-Hg-GSH by MRP3 (Vmax = 25.6 µM; Km = 2.8 µM) and MRP5 (Vmax = 32.9 µM; Km = 4.9 µM) was saturable. These findings are the first to show that MRP3 and MRP5 are capable of mediating the export of any form of mercury.