Contribution of a Mitochondrial Pathway to Excitotoxic Neuronal Necrosis
- Authors
- Seo, DW[Seo, Dae-Won]; Lopez-Meraz, ML[Lopez-Meraz, Maria-Leonor]; Allen, S[Allen, Suni]; Wasterlain, CG[Wasterlain, Claude Guy]; Niquet, J[Niquet, Jerome]
- Issue Date
- Jul-2009
- Publisher
- WILEY-LISS
- Keywords
- glutamate; mitochondrial swelling; cytochrome c; caspase-3; primary cortical culture
- Citation
- JOURNAL OF NEUROSCIENCE RESEARCH, v.87, no.9, pp.2087 - 2094
- Indexed
- SCIE
SCOPUS
- Journal Title
- JOURNAL OF NEUROSCIENCE RESEARCH
- Volume
- 87
- Number
- 9
- Start Page
- 2087
- End Page
- 2094
- URI
- https://scholarworks.bwise.kr/skku/handle/2021.sw.skku/77505
- DOI
- 10.1002/jnr.22035
- ISSN
- 0360-4012
- Abstract
- It is traditionally thought that excitotoxic necrosis is a passive mechanism that does not require the activation of a cell death program. In this study, we examined the contribution of the cytochrome c-dependent mitochondrial death pathway to excitotoxic neuronal necrosis, induced by exposing cultured cortical neurons to 1 mM glutamate for 6 hr and blocked by the NMDA antagonist, dizocilpine. Glutamate treatment induced early cytochrome c release, followed by activation of caspase-9 and caspase-3. Preincubation with the caspase-9 inhibitor z-LEHD-fmk, the caspase-3 inhibitor z-DEVD-fmk, or the specific pan-caspase inhibitor Q-VD-oph decreased the percentage of propidium iodide-positive neurons (52.5% +/- 3.1%, 39.4% +/- 3.5%, 44.6% +/- 3%, respectively, vs. 65% +/- 3% in glutamate + vehicle). EM studies showed mitochondrial release of cytochrome c in neurons in the early stages of necrosis and cleaved caspase-3 immunoreactivity in morphologically necrotic neurons. These results suggest that an active mechanism contributes to the demise of a sub-population of excitotoxic necrotic neurons. (C) 2009 Wiley-Liss, Inc.
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- Appears in
Collections - Medicine > Department of Medicine > 1. Journal Articles
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