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PMID:11146002

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Citation

Dargusch, R, Piasecki, D, Tan, S, Liu, Y and Schubert, D (2001) The role of Bax in glutamate-induced nerve cell death. J. Neurochem. 76:295-301

Abstract

The role of the Bax gene product was examined in three forms of cortical nerve cell death in primary cultures. These include spontaneous cell death, oxidative glutamate toxicity, in which exogenous glutamate inhibits cystine uptake resulting in toxic oxidative stress, and ionotropic glutamate receptor-mediated excitotoxicity following a brief exposure to 10 microM glutamate. Primary cortical and hippocampal neuron cultures were established from embryos of Bax -/+ x Bax -/+ matings and the embryos genotyped and assayed for cell death in the three experimental paradigms. Cell death induced by oxidative glutamate toxicity and glutamate-mediated excitotoxicity was not altered in the Bax -/- homozygous knockout animals. In contrast, there was an approximately 50% inhibition of spontaneous cell death. These results suggest that a classical Bax-dependent apoptotic pathway contributes to the spontaneous cell death that takes place when nerve cells are initially exposed to cell culture conditions. A Bax-dependent programmed cell death pathway is not, however, utilized in oxidative glutamate toxicity and NMDA receptor-mediated excitotoxicity following a brief exposure to low concentrations of glutamate.

Links

PubMed

Keywords

Animals; Apoptosis/genetics; Cell Death/genetics; Cell Survival/drug effects; Cell Survival/genetics; Cells, Cultured; Enzyme Inhibitors/pharmacology; Glutamic Acid/metabolism; Glutamic Acid/pharmacology; Heterozygote; Homozygote; Mice; Mice, Inbred BALB C; Mice, Knockout; Neurons/cytology; Neurons/drug effects; Neurons/metabolism; Oxidative Stress/drug effects; Oxidative Stress/genetics; Proto-Oncogene Proteins/deficiency; Proto-Oncogene Proteins/genetics; Proto-Oncogene Proteins/metabolism; Proto-Oncogene Proteins c-bcl-2; Receptors, Glutamate/metabolism; Receptors, N-Methyl-D-Aspartate/metabolism; Staurosporine/pharmacology; bcl-2-Associated X Protein

Significance

Annotations

Gene product Qualifier GO ID GO term name Evidence Code with/from Aspect Notes Status


See also

References

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