PT  - JOURNAL ARTICLE
AU  - David Schubert
AU  - Dana Piasecki
TI  - Oxidative Glutamate Toxicity Can Be a Component of the Excitotoxicity Cascade
AID  - 10.1523/JNEUROSCI.21-19-07455.2001
DP  - 2001 Oct 01
TA  - The Journal of Neuroscience
PG  - 7455--7462
VI  - 21
IP  - 19
4099  - http://www.jneurosci.org/content/21/19/7455.short
4100  - http://www.jneurosci.org/content/21/19/7455.full
SO  - J. Neurosci.2001 Oct 01; 21
AB  - Along with ionotropic and metabotropic glutamate receptors, the cystine/glutamate antiporter x may play a critical role in CNS pathology. High levels of extracellular glutamate inhibit the import of cystine, resulting in the depletion of glutathione and a form of cell injury called oxidative glutamate toxicity. Here we show that a portion of the cell death associated with NMDA receptor-initiated excitotoxicity can be caused by oxidative glutamate toxicity. In primary mouse cortical neurons the cell death resulting from the short-term application of 10 μmglutamate can be divided into NMDA and NMDA receptor-independent phases. The NMDA receptor-independent component is associated with high extracellular glutamate and is inhibited by a variety of reagents that block oxidative glutamate toxicity. These results suggest that oxidative glutamate toxicity toward neurons lacking functional NMDA receptors can be a component of the excitotoxicity-initiated cell death pathway.