Glutamate induces release of glutathione from cultured rat astrocytes--a possible neuroprotective mechanism?

Journal of Neurochemistry
João FradeSimon Heales

Abstract

Glutamate is the major excitatory amino acid of the mammalian brain but can be toxic to neurones if its extracellular levels are not tightly controlled. Astrocytes have a key role in the protection of neurones from glutamate toxicity, through regulation of extracellular glutamate levels via glutamate transporters and metabolic and antioxidant support. In this study, we report that cultures of rat astrocytes incubated with high extracellular glutamate (5 mM) exhibit a twofold increase in the extracellular concentration of the tripeptide antioxidant glutathione (GSH) over 4 h. Incubation with glutamate did not result in an increased release of lactate dehydrogenase, indicating that the rise in GSH was not because of membrane damage and leakage of intracellular pools. Glutamate-induced increase in extracellular GSH was also independent of de novo GSH synthesis, activation of NMDA and non-NMDA glutamate receptors or inhibition of extracellular GSH breakdown. Dose-response curves indicate that GSH release from rat astrocytes is significantly stimulated even at 0.1 mM glutamate. The ability of astrocytes to increase GSH release in the presence of extracellular glutamate could be an important neuroprotective mechanism enabling neurone...Continue Reading

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Citations

Mar 28, 2013·Neurotoxicity Research·Arik EisenkraftArseny Finkelstein
Jun 10, 2010·Toxicological Sciences : an Official Journal of the Society of Toxicology·Wojciech HilgierJan Albrecht
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Sep 16, 2009·Neurochemistry International·Karen Renata Matos OliveiraJosé Luiz Martins do Nascimento
Oct 8, 2021·Molecular Autism·Laurie-Anne Sapey-TriompheJohan Wagemans

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