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Transcriptional upregulation of nitric oxide synthase II by nuclear factor-kappaB promotes apoptotic neuronal cell death in the hippocampus following experimental status epilepticus.
J Neurosci Res. 2010 Jul; 88(9):1898-907.JN

Abstract

Whereas status epilepticus, or the condition of continuous epileptic seizures, produces a characteristic pattern of preferential neuronal cell loss in the hippocampus, the underlying mechanism is still unsettled. Based on an experimental model of temporal lobe status epilepticus, we demonstrated previously that prolonged seizures prompted an overproduction of nitric oxide (NO) by upregulation of NO synthase II (NOS II) in the hippocampal CA3 subfield, followed by the activation of mitochondrial apoptotic signaling cascade. Using the same animal model, the present study evaluated the hypothesis that transcriptional upregulation of NOS II gene by nuclear factor-kappaB (NF-kappaB) promotes apoptotic neuronal cell death in the hippocampus following status epilepticus. In Sprague-Dawley rats, significantly augmented nucleus-bound translocation of NF-kappaB p50 and p65 subunits and DNA binding activity of NF-kappaB were observed in hippocampal CA3 neurons as early as 30 min after elicitation of sustained seizure activity by microinjection of kainic acid into the CA3 subfield, followed by a progressive elevation that peaked at 90 min. In addition, application bilaterally into the hippocampal CA3 subfield of a selective NF-kappaB inhibitor, pyrrolidine dithiocarbamate or double-stranded kappaB decoy DNA significantly antagonized the activated NOS II-peroxynitrite signaling cascade (3 hr) and the associated manifestations of apoptotic cell death (7 days) in the hippocampus. We conclude that activation of NF-kappaB in hippocampal CA3 neurons upregulates NOS II gene expression following experimental temporal lobe status epilepticus, leading to apoptotic neuronal cell death in the hippocampus.

Authors+Show Affiliations

Department of Neurology, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung County, Taiwan, Republic of China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20155797

Citation

Chuang, Yao-Chung, et al. "Transcriptional Upregulation of Nitric Oxide Synthase II By Nuclear factor-kappaB Promotes Apoptotic Neuronal Cell Death in the Hippocampus Following Experimental Status Epilepticus." Journal of Neuroscience Research, vol. 88, no. 9, 2010, pp. 1898-907.
Chuang YC, Chen SD, Lin TK, et al. Transcriptional upregulation of nitric oxide synthase II by nuclear factor-kappaB promotes apoptotic neuronal cell death in the hippocampus following experimental status epilepticus. J Neurosci Res. 2010;88(9):1898-907.
Chuang, Y. C., Chen, S. D., Lin, T. K., Chang, W. N., Lu, C. H., Liou, C. W., Chan, S. H., & Chang, A. Y. (2010). Transcriptional upregulation of nitric oxide synthase II by nuclear factor-kappaB promotes apoptotic neuronal cell death in the hippocampus following experimental status epilepticus. Journal of Neuroscience Research, 88(9), 1898-907. https://doi.org/10.1002/jnr.22369
Chuang YC, et al. Transcriptional Upregulation of Nitric Oxide Synthase II By Nuclear factor-kappaB Promotes Apoptotic Neuronal Cell Death in the Hippocampus Following Experimental Status Epilepticus. J Neurosci Res. 2010;88(9):1898-907. PubMed PMID: 20155797.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Transcriptional upregulation of nitric oxide synthase II by nuclear factor-kappaB promotes apoptotic neuronal cell death in the hippocampus following experimental status epilepticus. AU - Chuang,Yao-Chung, AU - Chen,Shang-Der, AU - Lin,Tsu-Kung, AU - Chang,Wen-Neng, AU - Lu,Cheng-Hsien, AU - Liou,Chia-Wei, AU - Chan,Samuel H H, AU - Chang,Alice Y W, PY - 2010/2/16/entrez PY - 2010/2/16/pubmed PY - 2010/9/18/medline SP - 1898 EP - 907 JF - Journal of neuroscience research JO - J Neurosci Res VL - 88 IS - 9 N2 - Whereas status epilepticus, or the condition of continuous epileptic seizures, produces a characteristic pattern of preferential neuronal cell loss in the hippocampus, the underlying mechanism is still unsettled. Based on an experimental model of temporal lobe status epilepticus, we demonstrated previously that prolonged seizures prompted an overproduction of nitric oxide (NO) by upregulation of NO synthase II (NOS II) in the hippocampal CA3 subfield, followed by the activation of mitochondrial apoptotic signaling cascade. Using the same animal model, the present study evaluated the hypothesis that transcriptional upregulation of NOS II gene by nuclear factor-kappaB (NF-kappaB) promotes apoptotic neuronal cell death in the hippocampus following status epilepticus. In Sprague-Dawley rats, significantly augmented nucleus-bound translocation of NF-kappaB p50 and p65 subunits and DNA binding activity of NF-kappaB were observed in hippocampal CA3 neurons as early as 30 min after elicitation of sustained seizure activity by microinjection of kainic acid into the CA3 subfield, followed by a progressive elevation that peaked at 90 min. In addition, application bilaterally into the hippocampal CA3 subfield of a selective NF-kappaB inhibitor, pyrrolidine dithiocarbamate or double-stranded kappaB decoy DNA significantly antagonized the activated NOS II-peroxynitrite signaling cascade (3 hr) and the associated manifestations of apoptotic cell death (7 days) in the hippocampus. We conclude that activation of NF-kappaB in hippocampal CA3 neurons upregulates NOS II gene expression following experimental temporal lobe status epilepticus, leading to apoptotic neuronal cell death in the hippocampus. SN - 1097-4547 UR - https://www.unboundmedicine.com/medline/citation/20155797/Transcriptional_upregulation_of_nitric_oxide_synthase_II_by_nuclear_factor_kappaB_promotes_apoptotic_neuronal_cell_death_in_the_hippocampus_following_experimental_status_epilepticus_ L2 - https://doi.org/10.1002/jnr.22369 DB - PRIME DP - Unbound Medicine ER -