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

doi:10.1016/j.neulet.2004.03.033

Neuroscience Letters

Volume 362, Issue 3, 27 May 2004, Pages 253-257

https://doi.org/10.1016/j.neulet.2004.03.033 Get rights and content

Abstract

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 x_c⁻, 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.

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Acknowledgments

We thank David Schubert for HT22 cells, Vishva M. Dixit, Ingrid E. Wertz, Jakob Troppmair and Jeong-Sun Seo for plasmids and Libby Guethlein for critical reading of the manuscript. This work was supported by the Deutsche Forschungsgemeinschaft (DFG) via SFB 530 and HOMFOR.

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¹: These authors contributed equally to the study.

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

Abstract

Section snippets

Acknowledgments

Brain Res.

Biochem. Pharmacol.

J. Biol. Chem.

Selenium and selenoproteins in the brain and brain diseases

J. Neurochem.

Neurons overexpressing heme oxygenase-1 resist oxidative stress-mediated cell death

J. Neurochem.

The role of monoamine metabolism in oxidative glutamate toxicity

J. Neurosci.

Signaling by reactive oxygen species in the nervous system

Cell. Mol. Life Sci.