کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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4348100 | 1296877 | 2008 | 6 صفحه PDF | دانلود رایگان |
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 NG-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.
Journal: Neuroscience Letters - Volume 443, Issue 3, 10 October 2008, Pages 134–139