Multidrug resistance protein 1-mediated export of glutathione and glutathione disulfide from brain astrocytes.
Many cell types are known to release glutathione (GSH) and glutathione disulfide (GSSG). Multidrug resistance proteins (Mrps) have been identified to be involved in these export processes. In the brain, astrocytes have key functions in GSH metabolism and in antioxidative defense. These cells release large amounts of GSH under unstressed conditions as well as GSSG during oxidative stress. This chapter describes experimental paradigms to analyze the release of the physiological Mrp substrates GSH and GSSG from cultured astrocytes. These assay systems can be used to screen for compounds that affect Mrp1-mediated export from astrocytes and therefore could interfere with the antioxidative defense system of the brain. In addition, our methods could be useful in investigating mechanisms of export of GSH and GSSG from other cell types.
Hirrlinger
Johannes
J
Max-Planck Institute for Experimental Medicine, Department of Neurogenetics, Göttingen, Germany.
Dringen
Ralf
R
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors / Q000502:physiology*; D000818:Animals; D000975:Antioxidants / Q000032:analysis / Q000494:pharmacology; D001253:Astrocytes / Q000378:metabolism*; D001921:Brain / Q000166:cytology / Q000378:metabolism*; D002470:Cell Survival; D002478:Cells, Cultured; D005978:Glutathione / Q000378:metabolism* / Q000494:pharmacology; D019803:Glutathione Disulfide / Q000378:metabolism* / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000032:analysis; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000975:Antioxidants; D006861:Hydrogen Peroxide; D007770:L-Lactate Dehydrogenase; D005978:Glutathione; D019803:Glutathione Disulfide