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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Dawson, T. M. Herring, W. J. Dawson, V. L. Ahn, S. Ginty, D. D. Gonzalez-zulueta, M. Sasaki, M. Huang, H. |
| Description | Author Affiliation: Sasaki M ( Departments of Neurology, Neuroscience, and Physiology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.); |
| Abstract | Neuronal nitric oxide (NO) synthase (nNOS) is dynamically regulated in response to a variety of physiologic and pathologic stimuli. Although the dynamic regulation of nNOS is well established, the molecular mechanisms by which such diverse stimuli regulate nNOS expression have not yet been identified. We describe experiments demonstrating that Ca(2+) entry through voltage-sensitive Ca(2+) channels regulates nNOS expression through alternate promoter usage in cortical neurons and that nNOS exon 2 contains the regulatory sequences that respond to Ca(2+). Deletion and mutational analysis of the nNOS exon 2 promoter reveals two critical cAMP/Ca(2+) response elements (CREs) that are immediately upstream of the transcription start site. CREB binds to the CREs within the nNOS gene. Mutation of the nNOS CREs as well as blockade of CREB function results in a dramatic loss of nNOS transcription. These findings suggest that nNOS is a Ca(2+)-regulated gene through the interactions of CREB on the CREs within the nNOS exon 2 promoter and that these interactions are likely to be centrally involved in the regulation of nNOS in response to neuronal injury and activity-dependent plasticity. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 15 |
| Volume Number | 97 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2000-08-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Calcium Metabolism Cyclic AMP Response Element-Binding Protein Gene Expression Regulation, Enzymologic Nitric Oxide Synthase Genetics Transcription, Genetic Animals Calcium Channels, L-Type Cell Membrane Physiology Cells, Cultured Cerebral Cortex Cytology DNA, Complementary Enzyme Induction Exons Mice Molecular Sequence Data Nitric Oxide Synthase Type I Promoter Regions, Genetic RNA, Messenger Response Elements Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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