[Cerebral oxidative stress: are astrocytes vulnerable to low intracellular glutamate concentrations? Consequences for neuronal viability].
This review describes reactive oxygen species (ROS), their production and effects on crucial biological molecules, the different lines of defense against oxidative stress, with particular attention to glutathione, the main antioxidant in the brain, which neuronal synthesis seems to be dependent on astrocytic precursors. It also focuses on the different ways by which glutamate may induce oxidative stress in the brain. The different mechanisms leading to ROS production, activated during the excitotoxic cascade, are described. Oxidative glutamate toxicity is also briefly described. A novel form of oxidative glutamate toxicity by depletion of transported glutamate that we recently evidenced is detailed. This toxicity induced by pharmacological reversal of glutamate transport, which mimics glutamate transport reversal occurring in ischemia, involves glutathione depletion and oxidative stress, leading to delayed death of cultured striatal astrocytes differentiated by dibutyryl-cAMP, probably through apoptotic processes. Evidence suggesting that this oxidative glutamate toxicity by depletion of transported glutamate is very likely occurring in vivo and its consequences on neuronal survival are discussed.
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Interactions cellulaires, neurodégénérescence et neuroplasticité (IC2 N), UMR 6186 du CNRS, 31 chemin Joseph-Aiguier, 13402 Marseille cedex 20, France.
Nafia
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Nieoullon
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Kerkerian Le Goff
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Had-Aissouni
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D000975:Antioxidants / Q000502:physiology; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D001692:Biological Transport / Q000187:drug effects; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D003994:Bucladesine / Q000494:pharmacology; D002450:Cell Communication; D002454:Cell Differentiation; D002470:Cell Survival; D002478:Cells, Cultured / Q000473:pathology; D018698:Glutamic Acid / Q000378:metabolism / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D015227:Lipid Peroxidation; D008928:Mitochondria / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000473:pathology*; D018384:Oxidative Stress; D017382:Reactive Oxygen Species
D000975:Antioxidants; D009419:Nerve Tissue Proteins; D017382:Reactive Oxygen Species; D018698:Glutamic Acid; D003994:Bucladesine; D005978:Glutathione