Generation of reactive oxygen species, release of L-glutamate and activation of caspases are required for oxygen-induced apoptosis of embryonic hippocampal neurons in culture
Y. Ishikawa et al., Generation of reactive oxygen species, release of L-glutamate and activation of caspases are required for oxygen-induced apoptosis of embryonic hippocampal neurons in culture, BRAIN RES, 824(1), 1999, pp. 71-80
Oxygen-induced cell death in embryonic neurons is a useful in vitro model o
f neuronal apoptosis to study the molecular mechanisms underlying the cell
death induced by oxidative stress. In the present study, we examined the in
volvement of reactive oxygen species and glutamate in the high (50%) oxygen
-induced death of cultured hippocampal neurons. During the course of cell d
eath, increases in O-2(-) and hydrogen peroxide (H2O2) levels were observed
. On the other hand, superoxide dismutase (SOD), catalase and deferoxamine
(DFX), which have inhibitory effects on the generation of O-2(-), H2O2 and
hydroxyl radicals, respectively, protected the neurons. These results sugge
sted that both O-2(-) and H2O2 play important roles in this apoptosis. Anta
gonists of NMDA and AMPA/kinate (AMPA/KA) receptors and an inhibitor of glu
tamate release partially prevented the apoptosis, suggesting that exposure
to high oxygen enhances glutamate release, which results in activation of N
MDA receptor and AMPA/KA receptor. In addition, specific nitric oxide (NO)
scavenger and NO synthetase inhibitors blocked the apoptosis, indicating th
at NO and/or peroxynitrite are involved in this mechanism of cell death. Ca
spase inhibitors also blocked the neuronal apoptosis. These results suggest
ed that multiple effecters including generation of reactive oxygen species,
release of L-glutamate and activation of caspases are activated during the
death induced by high oxygen. (C) 1999 Elsevier Science B.V. All rights re
served.