PT  - JOURNAL ARTICLE
AU  - Yong Chen
AU  - Reas S. Khan
AU  - Alyssa Cwanger
AU  - Ying Song
AU  - Catherine Steenstra
AU  - Sookhee Bang
AU  - Jaime H. Cheah
AU  - Joshua Dunaief
AU  - Kenneth S. Shindler
AU  - Solomon H. Snyder
AU  - Sangwon F. Kim
TI  - Dexras1, a Small GTPase, Is Required for Glutamate-NMDA Neurotoxicity
AID  - 10.1523/JNEUROSCI.1497-12.2013
DP  - 2013 Feb 20
TA  - The Journal of Neuroscience
PG  - 3582--3587
VI  - 33
IP  - 8
4099  - http://www.jneurosci.org/content/33/8/3582.short
4100  - http://www.jneurosci.org/content/33/8/3582.full
SO  - J. Neurosci.2013 Feb 20; 33
AB  - Dexras1, a small G-protein localized predominantly to the brain, is transcriptionally upregulated by the synthetic glucocorticoid dexamethasone. It has close homology to the Ras subfamily but differs in that Dexras1 contains an extended 7 kDa C-terminal tail. Previous studies in our laboratory showed that NMDA receptor activation, via NO and Dexras1, physiologically stimulates DMT1, the major iron importer. A membrane-permeable iron chelator substantially reduces NMDA excitotoxicity, suggesting that Dexras1-mediated iron influx plays a crucial role in NMDA/NO-mediated cell death. We here report that iron influx is elicited by nitric oxide but not by other proapoptotic stimuli, such as H2O2 or staurosporine. Deletion of Dexras1 in mice attenuates NO-mediated cell death in dissociated primary cortical neurons and retinal ganglion cells in vivo. Thus, Dexras1 appears to mediate NMDA-elicited neurotoxicity via NO and iron influx.