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.
Rössler
Oliver G
OG
Department of Medical Biochemistry and Molecular Biology, University of Saarland Medical Center, D-66421 Homburg, Germany.
Bauer
Inge
I
Chung
Hee-Yong
HY
Thiel
Gerald
G
D000818:Animals; D016923:Cell Death / Q000187:drug effects*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005786:Gene Expression Regulation; D018014:Gene Transfer Techniques; D018698:Glutamic Acid / Q000494:pharmacology; D018840:HSP70 Heat-Shock Proteins / Q000494:pharmacology*; D006419:Heme Oxygenase (Decyclizing) / Q000494:pharmacology*; D051547:Heme Oxygenase-1; D006624:Hippocampus / Q000166:cytology*; D008565:Membrane Proteins; D051379:Mice; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000502:physiology; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000378:metabolism; D018038:Sodium Selenite / Q000494:pharmacology*
D016895:Culture Media, Serum-Free; D018840:HSP70 Heat-Shock Proteins; D008565:Membrane Proteins; D016328:NF-kappa B; D018696:Neuroprotective Agents; D016755:Proto-Oncogene Proteins c-jun; D018698:Glutamic Acid; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse; D018038:Sodium Selenite