Journal
NEUROSCIENCE LETTERS
Volume 443, Issue 3, Pages 134-139Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.neulet.2008.07.060
Keywords
nitric oxide; endoplasmic reticulum stress; GRP78; caspase-12; apoptosis; febrile seizure
Categories
Funding
- National Natural Science Foundation of China [30571969]
- Key Construction Program of the National 985 Project [985-2-011-24]
- Doctoral Program of Higher Education of China [20040001114]
- Beijing Municipal Natural Science Foundation [7063096]
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Nitric oxide (NO), as a neurotransmitter, exerts various physiological and pathological effects on the brain. Excess NO is toxic to neurons and may cause neuronal apoptosis. However, the cascade of NO-mediated apoptosis is not fully understood. We utilized a recurrent febrile seizures (FS) rat model and found that plasma NO was increased, neuronal apoptosis was evident, the expression of glucose-regulated Protein78 (GRP78, a well-established marker of ER stress) was elevated, and caspase-12 (an ER stress-specific proapoptosis molecule) was activated in the hippocampus in a time-dependent manner after recurrent FS. Administration of sodium nitroprusside (SNP, an NO donor) enhanced neuronal apoptosis, down-regulated the expression of GRP78, and increased that of caspase-12 in FS + SNP groups compared with FS groups. In contrast, treatment with N-G-nitrol-L-arginine methyl ester (L-NAME, a competitive NO synthase inhibitor) inhibited neuronal apoptosis, up-regulated the expression of GRP78, and decreased that of caspase-12 in FS + L-NAME groups compared with FS groups. These results suggest that NO mediates neuronal apoptosis caused by recurrent FS, and that the ER stress pathway is involved in NO-mediated neuronal apoptosis. (C) 2008 Elsevier Ireland Ltd. All rights reserved.
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