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J. Biol. Chem., Vol. 275, Issue 22, 16879-16884, June 2, 2000
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Regulation of Neuronal Cell Adhesion Molecule Expression by NF-kappa B*

Carol S. Simpson and Brian J. MorrisDagger

From the Division of Neuroscience and Biomedical Systems, Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow G12 8QQ, United Kingdom

The neuronal cell adhesion molecule (NCAM) is a key mediator of structural plasticity in the central nervous system, but the mechanisms that control its expression are unknown. Equally, although the transcription factor NF-kappa B is present in the brain, few NF-kappa B-regulated genes relevant for central nervous system function have been identified. We have previously demonstrated that NF-kappa B is activated in neuronal cultures treated with kainic acid or nitric oxide. We show here that kainic acid or nitric oxide also increase the levels of NCAM mRNA and protein in neurons and that this induction of NCAM expression is sensitive to dexamethasone and to antisense, but not missense, oligonucleotides designed to suppress NF-kappa B synthesis. Nitric oxide also stimulates protein binding to an NF-kappa B site in the promoter of the NCAM gene. This indicates that NF-kappa B, which has recently been implicated in synaptic plasticity and also in the etiology of neurodegenerative disease, plays a crucial role in the activity-dependent regulation of NCAM gene expression. In addition, since both NCAM and NF-kappa B are present in the post-synaptic density, this represents a route allowing direct communication between the synapse and the nucleus.

* This work was supported by Wellcome Trust Grant 045837.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Dagger To whom correspondence should be addressed: Division of Neuroscience and Biomedical Systems, Institute of Biomedical and Life Sciences, West Medical Bldg., University of Glasgow, Glasgow G12 8QQ, UK. Tel.: 44-141-330-5361; Fax: 44-141-330-5659; E-mail: B.Morris@biomed.gla.ac.uk.

Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.
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