Nox4-dependent H2O2 production contributes to chronic glutamate toxicity in primary cortical neurons

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Title
Nox4-dependent H2O2 production contributes to chronic glutamate toxicity in primary cortical neurons
Author(s)
Jong Seong Ha; J E Lee; Jae-Ran Lee; C S Lee; J S Maeng; Y S Bae; Ki Sun KwonSung Sup Park
Bibliographic Citation
Experimental Cell Research, vol. 316, no. 10, pp. 1651-1661
Publication Year
2010
Abstract
Reactive oxygen species (ROS) can trigger neuronal cell death and has been implicated in a variety of neurodegenerative diseases as well as brain ischemia. Here, we demonstrate that chronic (but not acute) glutamate toxicity in primary cortical neuronal cultures is associated with hydrogen peroxide (H2O2) accumulation in the culture medium and that neurotoxicity can be eliminated by external catalase treatment. Neuronal cultures in Ca2+-free medium or treated with BAPTA showed reduced glutamate-induced H2O2 generation, indicating that H2O2 generation is Ca2+-dependent. Pharmacological and genetic approaches revealed that NADPH oxidase plays a role in glutamate-induced H2O2 generation and that activation of NMDA and AMPA receptors is involved in this H2O2 generation. The Nox4 siRNA reduced NMDA-induced H2O2 production by 54% and cytotoxicity in parallel, suggesting that Nox4-containing NADPH oxidase functions NMDA receptor-mediated H2O2 production resulting in neurotoxicity. These findings suggest that the modulation of NADPH oxidase can be used as a new therapeutic strategy for glutamate-induced neuronal diseases.
Keyword
Chronic exposureGlutamate toxicityNox4Reactive oxygen species
ISSN
0014-4827
Publisher
Elsevier
DOI
http://dx.doi.org/10.1016/j.yexcr.2010.03.021
Type
Article
Appears in Collections:
Division of Biomedical Research > Rare Disease Research Center > 1. Journal Articles
Division of Research on National Challenges > Aging Research Center > 1. Journal Articles
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