Journal
CELL DEATH AND DIFFERENTIATION
Volume 7, Issue 5, Pages 470-476Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.cdd.4400678
Keywords
metabotropic glutamate receptor; apoptosis; necrosis; neuronal death
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- PHS HHS [R49 CCR306634-07] Funding Source: Medline
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Glutamate released during acute CNS insults acts at metabotropic glutamate receptors (mGluR), including group I mGluR, Blockade of group I mGluR during in vitro neuronal trauma provides neuroprotection, whereas activation exacerbates such injury. However, the effects of group I mGluR agonists or antagonists have been primarily studied in in vitro models characterized by necrotic cell death. We examined the role of group I mGluR in the modulation of neuronal injury induced during oxygen-glucose deprivation (OGD), a well-studied model of necrosis, and by application of two well established pro-apoptotic agents: staurosporine and etoposide. Inhibition of group I mGluR attenuated necrosis induced by OGD, whereas selective activation of group 1 mGluR exacerbated such injury. In contrast, activation of group I mGluR, including selective activation of mGluR5, significantly attenuated apoptotic cell death induced by both staurosporine and etoposide, This effect was completely reversed by coapplication of a group I mGluR antagonist. Thus, group I mGluR appear to exhibit opposite effects on necrotic and apoptotic neuronal cell death. Our findings suggest that activation of mGluR1 exacerbates neuronal necrosis whereas both mGluR1 and mGluR5 play a role in attenuation of neuronal apoptosis.
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