Upregulation of nitric oxide synthase II contributes to apoptotic cell death in the hippocampal CA3 subfield via a cytochrome c/caspase-3 signaling cascade following induction of experimental temporal lobe status epilepticus in the rat

Status epilepticus results in preferential neuronal cell loss in the hippocampus. We evaluated the hypothesis that the repertoire of intracellular events in the vulnerable hippocampal CA3 subfield after induction of experimental temporal lobe status epilepticus entails upregulation of nitric oxide s...

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Bibliographic Details
Published in:Neuropharmacology 2007-04, Vol.52 (5), p.1263-1273
Main Authors: Chuang, Y.C., Chen, S.D., Lin, T.K., Liou, C.W., Chang, W.N., Chan, S.H.H., Chang, A.Y.W.
Format: Article
Language:English
Subjects:
Animals
Apoptosis
Apoptosis - physiology
Blotting, Western
Caspase 3 - physiology
Caspase-3
Cytochrome c
Cytochromes c - physiology
Cytosol - enzymology
DNA Fragmentation - drug effects
Electroencephalography - drug effects
Enzyme Inhibitors - pharmacology
Epilepsy, Temporal Lobe - physiopathology
Experimental temporal lobe status epilepticus
Fluorescent Antibody Technique
Functional Laterality - physiology
Hippocampal CA3 subfield
Hippocampus - cytology
Hippocampus - physiology
In Situ Nick-End Labeling
Male
Microscopy, Confocal
Nitric Oxide - biosynthesis
Nitric Oxide - physiology
Nitric oxide synthase II
Nitric Oxide Synthase Type II - antagonists & inhibitors
Nitric Oxide Synthase Type II - biosynthesis
Rats
Rats, Sprague-Dawley
Signal Transduction - physiology
Status Epilepticus - physiopathology
Up-Regulation - drug effects
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Summary:Status epilepticus results in preferential neuronal cell loss in the hippocampus. We evaluated the hypothesis that the repertoire of intracellular events in the vulnerable hippocampal CA3 subfield after induction of experimental temporal lobe status epilepticus entails upregulation of nitric oxide synthase II (NOS II), followed by the release of mitochondrial cytochrome c that triggers the cytosolic caspase-3 cascade, leading to apoptotic cell death. In Sprague–Dawley rats, significant and temporally correlated upregulation of NOS II (3–24h), but not NOS I or II expression, enhanced cytosolic translocation of cytochrome c (days 1 and 3), augmented activated caspase-3 in cytosol (days 1, 3 and 7) and DNA fragmentation (days 1, 3 and 7) was detected bilaterally in the hippocampal CA3 subfield after elicitation of sustained seizure activity by microinjection of kainic acid into the unilateral CA3 subfield. Application bilaterally into the hippocampal CA3 subfield of a selective NOS II inhibitor, S-methylisothiourea, significantly blunted these apoptotic events; a selective NOS I inhibitor, Nω-propyl-l-arginine or a potent NOS III inhibitor, N5-(1-iminoethyl)-l-ornithine was ineffective. We conclude that upregulation of NOS II contributes to apoptotic cell death in the hippocampal CA3 subfield via a cytochrome c/caspase-3 signaling cascade following the induction of experimental temporal lobe status epilepticus.
ISSN:0028-3908
1873-7064
DOI:10.1016/j.neuropharm.2007.01.010