The activation of metabotropic glutamate receptors protects nerve cells from oxidative stress.
Metabotropic glutamate receptors (mGluRs) have been implicated in a variety of cellular responses to glutamic acid. The work described in this manuscript extends the role of mGluRs to include protection from oxidative stress-induced programmed cell death. Glutamate analogs regulate inositol-1,4,5 triphosphate mass accumulation in accordance with their ability to protect cells from oxidative glutamate toxicity, and protection appears to take place at the level of glutathione metabolism. Short-term exposure of cells to low concentrations of glutamate desensitizes cells to a subsequent challenge from glutamate. Glutamate exposure upregulates the expression of mGluR5 in hippocampal HT-22 cells and mGluR1 in cortical primary cultures. Finally, group I mGluR agonists also protect cells from death programs initiated by glucose starvation and cystine deprivation.
Cellular Neurobiology Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037, USA.
Y
Y
Sagara
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Schubert
D000818:Animals; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000502:physiology*; D005978:Glutathione / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000187:drug effects / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
D018094:Receptors, Metabotropic Glutamate; D005978:Glutathione