These authors contributed equally to this work.
The multidrug resistance protein 1 (Mrp1), but not Mrp5, mediates export of glutathione and glutathione disulfide from brain astrocytes
Article first published online: 15 MAR 2006
Journal of Neurochemistry
Volume 97, Issue 2, pages 373–384, April 2006
How to Cite
Minich, T., Riemer, J., Schulz, J. B., Wielinga, P., Wijnholds, J. and Dringen, R. (2006), The multidrug resistance protein 1 (Mrp1), but not Mrp5, mediates export of glutathione and glutathione disulfide from brain astrocytes. Journal of Neurochemistry, 97: 373–384. doi: 10.1111/j.1471-4159.2006.03737.x
- Issue published online: 15 MAR 2006
- Article first published online: 15 MAR 2006
- Received November 3, 2005; revised manuscript received December 16, 2005; accepted December 19, 2005.
- glutathione disulfide export;
- glutathione transport;
- multidrug resistance proteins;
- oxidative stress
Astrocytes play an important role in the glutathione (GSH) metabolism of the brain. To test for an involvement of multidrug resistance protein (Mrp) 1 and 5 in the release of GSH and glutathione disulfide (GSSG) from astrocytes, we used astrocyte cultures from wild-type, Mrp1-deficient [Mrp1(–/–)] and Mrp5-deficient [Mrp5(–/–)] mice. During incubation of wild-type or Mrp5(–/–) astrocytes, GSH accumulated in the medium at a rate of about 3 nmol/(h.mg), whereas the export of GSH from Mrp1(–/–) astrocytes was only one-third of that. In addition, Mrp1(–/–) astrocytes had a 50% higher specific GSH content than wild-type or Mrp5(–/–) cells. The presence of 50 μm of the Mrp inhibitor MK571 inhibited the rate of GSH release from wild-type and Mrp5(–/–) astrocytes by 60%, but stimulated at the low concentration of 1 μm GSH release by 40%. In contrast, both concentrations of MK571 did not affect GSH export from Mrp1(–/–) astrocytes. Moreover, in contrast to wild-type and Mrp5(–/–) cells, GSSG export during H2O2 stress was not observed for Mrp1(–/–) astrocytes. These data demonstrate that in astrocytes Mrp1 mediates 60% of the GSH export, that Mrp1 is exclusively responsible for GSSG export and that Mrp5 does not contribute to these transport processes.