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The Journal of Neuroscience, September 1, 1998, 18(17):6662-6671
The Activation of Metabotropic Glutamate Receptors Protects Nerve Cells from Oxidative Stress
Yutaka Sagara and David Schubert Cellular Neurobiology Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037
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.
Key words: metabotropic receptors; oxidative stress; glutamate; toxicity; cell death; cystine
Copyright © 1998 Society for Neuroscience 0270-6474/98/18176662-10$05.00/0
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