Glutamate-induced oxidative stress, but not cell death, is largely dependent upon extracellular calcium in mouse neuronal HT22 cells
- PMID: 16229947
- DOI: 10.1016/j.neulet.2005.09.056
Glutamate-induced oxidative stress, but not cell death, is largely dependent upon extracellular calcium in mouse neuronal HT22 cells
Abstract
Elucidating the relationship of glutamate-induced Ca2+ flux and oxidative death of neuronal cells may be of great relevance for neurodegenerative diseases in human beings. Mouse hippocampal HT22 cells provide a model system to study this relationship at the molecular level. Here we show that stimulation of HT22 cells with 5 mM glutamate is cytotoxic. Glutamate-induced cytotoxicity was associated with the generation of reactive oxygen species (ROS) and activation of the death executioner caspases 1 and 3. Treatment of HT22 cells with the calcium chelator, EGTA, and the calcium channel blocker, CoCl2, revealed that glutamate-induced cell death was dependent, in part, on glutamate-induced Ca2+ influx from extracellular stores. However, activation of caspases 1 and 3 and death of HT22 cells were also observed when Ca2+ was lacking in the extracellular milieu and ROS production abrogated. These findings led us to conclude that glutamate-induced death of mouse HT22 cells utilizes a complex mechanism that relies only in part on Ca2+ influx and ROS production. Additional studies are warranted to evaluate glutamate-induced death mechanisms that operate independently of Ca2+ influx and generation of ROS.
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