Glutamate-induced cell death of immortalized murine hippocampal neurons: neuroprotective activity of heme oxygenase-1, heat shock protein 70, and sodium selenite.

HT22 immortalized hippocampal neurons serve as a cellular model system to study oxidative stress, an imbalance of cellular redox homeostasis. Glutamate induces HT22 cell death by inhibiting the uptake of cystine into the cells via the cystine/glutamate transport system xc-, thus leading to reduced levels of glutathione. Here, we show that glutamate-induced cell death is attenuated in HT22 cells overexpressing heat shock protein 70 or heme oxygenase-1. Moreover, supplementing the culture medium with sodium selenite completely protected HT22 against oxidative glutamate toxicity. In contrast, neither heat shock protein 70 nor heme oxygenase-1 expression or increased concentrations of sodium selenite protected HT22 cells against serum withdrawal-induced cell death. These data indicate that glutamate-induced cell death differs substantially from that induced by growth factor deprivation. Copyright 2004 Elsevier Ireland Ltd.