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Astroglial glutathione export and the supply of glutathione precursors to neurons
Author(s) -
Dringen R.,
Hirrlinger J.
Publication year - 2003
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.85.s2.9_2.x
Subject(s) - glutathione , extracellular , biochemistry , cysteine , glutamate receptor , glutamine , glycine , dipeptide , amino acid , astrocyte , intracellular , biology , neuroglia , microbiology and biotechnology , chemistry , enzyme , central nervous system , neuroscience , receptor
Neurons rely on the availability of extracellular cysteine for their glutathione (GSH) synthesis. This amino acid is generated by processing of extracellular GSH. Astrocytes play an important role in the GSH metabolism of the brain, since of the different brain cell type investigated only astrocytes release substantial amounts of GSH. The multidrug resistance protein 1 (Mrp1) which is expressed in astrocytes in vitro and in vivo mediates about 60% of the GSH release from cultured astrocytes. Extracellular GSH serves as substrate for the astroglial ectoenzyme gamma‐glutamyl transpeptidase (gGT). Inhibition of this enzyme prevents the astroglia‐mediated increase in the GSH level of cocultured neurons. The dipeptide CysGly, which is produced by gGT, is hydrolysed by the neuronal aminopeptidase N to glycine and cysteine. By providing the glutamate‐precursor glutamine and the dipeptide CysGly astrocytes supply to neurons precursors for all three amino acids which are required for neuronal GSH synthesis.