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- Title
Dexras1, a Small GTPase, Is Required for Glutamate-NMDA Neurotoxicity.
- Authors
Chen, Yong; Khan, Reas S.; Cwanger, Alyssa; Song, Ying; Steenstra, Catherine; Bang, Sookhee; Cheah, Jaime H.; Dunaief, Joshua; Shindler, Kenneth S.; Snyder, Solomon H.; Kim, Sangwon F.
- Abstract
Dexras1, a small G-protein localized predominantly to the brain, is transcriptionally upregulated by the synthetic glucocorticoid dexa-methasone. It has close homology to the Ras subfamily but differs in that Dexrasl 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 Dexrasl-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 Dexrasl in mice attenuates NO-mediated cell death in dissociated primary cortical neurons and retinal ganglion cells in vivo. Thus, Dexrasl appears to mediate NMDA-elicited neurotoxicity via NO and iron influx.
- Subjects
GUANOSINE triphosphatase; GLUTAMIC acid; METHYL aspartate; NEUROTOXICOLOGY; G proteins; GENETIC transcription; GLUCOCORTICOIDS; DEXAMETHASONE; STAUROSPORINE
- Publication
Journal of Neuroscience, 2013, Vol 33, Issue 8, p3582
- ISSN
0270-6474
- Publication type
Article
- DOI
10.1523/JNEUROSCI.1497-12.2013