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The role of Bax in glutamate‐induced nerve cell death
Author(s) -
Dargusch Richard,
Piasecki Dana,
Tan Shirlee,
Liu Yuanbin,
Schubert David
Publication year - 2001
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2001.00035.x
Subject(s) - excitotoxicity , glutamate receptor , programmed cell death , nmda receptor , microbiology and biotechnology , biology , apoptosis , oxidative stress , receptor , biochemistry
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 µ m glutamate. Primary cortical and hippocampal neuron cultures were established from embryos of Bax –/+× 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 programed 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.