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Glial‐derived arginine, the nitric oxide precursor, protects neurons from NMDA‐induced excitotoxicity
Author(s) -
Grima Gilbert,
Benz Beatrix,
Do Kim Q.
Publication year - 2001
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1046/j.0953-816x.2001.01799.x
Subject(s) - excitotoxicity , peroxynitrite , nmda receptor , glutamate receptor , neuroprotection , nitric oxide , chemistry , microbiology and biotechnology , programmed cell death , neuroscience , receptor , superoxide , biochemistry , biology , apoptosis , organic chemistry , enzyme
Excitotoxic neuronal cell death is characterized by an overactivation of glutamate receptors, in particular of the NMDA subtype, and the stimulation of the neuronal nitric oxide synthase (nNOS), which catalyses the formation of nitric oxide (NO) from l ‐arginine (L‐Arg). At low L‐Arg concentrations, nNOS generates NO and superoxide (O 2 • – ), favouring the production of the toxin peroxynitrite (ONOO – ). Here we report that NMDA application for five minutes in the absence of added L‐Arg induces neuronal cell death, and that the presence of L‐Arg during NMDA application prevents cell loss by blocking O 2 • – and ONOO – formation and by inhibiting mitochondrial depolarization. Because L‐Arg is transferred from glial cells to neurons upon activation of glial glutamate receptors, we hypothesized that glial cells play an important modulator role in excitotoxicity by releasing L‐Arg. Indeed, as we further show, glial‐derived L‐Arg inhibits NMDA‐induced toxic radical formation, mitochondrial dysfunction and cell death. Glial cells thus may protect neurons from excitotoxicity by supplying L‐Arg. This potential neuroprotective mechanism may lead to an alternative approach for the treatment of neurodegenerative diseases involving excitotoxic processes, such as ischemia.