| Online-Ressource |
Verfasst von: | Zhang, Sheng-Jia [VerfasserIn]  |
| Buchthal, Bettina [VerfasserIn]  |
| Lau, David [VerfasserIn]  |
| Hayer, Stefanie Nicole [VerfasserIn]  |
| Dick, Oliver [VerfasserIn]  |
| Schwaninger, Markus [VerfasserIn]  |
| Veltkamp, Roland [VerfasserIn]  |
| Zou, Ming [VerfasserIn]  |
| Weiss, Ursula [VerfasserIn]  |
| Bading, Hilmar [VerfasserIn]  |
Titel: | A signaling cascade of nuclear calcium-CREB-ATF3 activated by synaptic NMDA receptors defines a gene repression module that protects against extrasynaptic NMDA receptor-induced neuronal cell death and ischemic brain damage |
Verf.angabe: | Sheng-Jia Zhang, Bettina Buchthal, David Lau, Stefanie Hayer, Oliver Dick, Markus Schwaninger, Roland Veltkamp, Ming Zou, Ursula Weiss, and Hilmar Bading |
E-Jahr: | 2011 |
Jahr: | March 30, 2011 |
Umfang: | 13 S. |
Fussnoten: | Gesehen am 16.01.2023 |
Titel Quelle: | Enthalten in: The journal of neuroscience |
Ort Quelle: | Washington, DC : Soc., 1981 |
Jahr Quelle: | 2011 |
Band/Heft Quelle: | 31(2011), 13, Seite 4978-4990 |
ISSN Quelle: | 1529-2401 |
Abstract: | Synapse-to-nucleus signaling triggered by synaptic NMDA receptors can lead to the buildup of a neuroprotective shield. Nuclear calcium activating the cAMP response element binding protein (CREB) plays a key role in neuroprotection acquired by synaptic activity. Here we show that in mouse hippocampal neurons, the transcription factor Atf3 (activating transcription factor 3) is a direct target of CREB. Induction of ATF3 expression by CREB in hippocampal neurons was initiated by calcium entry through synaptic NMDA receptors and required nuclear calcium transients and calcium/calmodulin-dependent protein kinase IV activity. Acting as a transcriptional repressor, ATF3 protects cultured hippocampal neurons from apoptosis and extrasynaptic NMDA receptor-induced cell death triggered by bath application of NMDA or oxygen-glucose deprivation. Expression of ATF3 in vivo using stereotaxic delivery of recombinant adeno-associated virus reduces brain damage following a cerebral ischemic insult in mice. Conversion of ATF3 to a transcriptional activator transforms ATF3 into a potent prodeath protein that kills neurons in cell culture and, when expressed in vivo in the hippocampus, ablates the neuronal cell layer. These results link nuclear calcium-CREB signaling to an ATF3-mediated neuroprotective gene repression program, indicating that activity-dependent shutoff of genes is an important process for survival. ATF3 supplementation may counteract age- and disease-related neuronal cell loss caused by a reduction in synaptic activity, malfunctioning of calcium signaling toward and within the nucleus (“nuclear calciopathy”), or increases in death signaling by extrasynaptic NMDA receptors. |
DOI: | doi:10.1523/JNEUROSCI.2672-10.2011 |
URL: | Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.
Volltext: https://doi.org/10.1523/JNEUROSCI.2672-10.2011 |
| Volltext: https://www.jneurosci.org/content/31/13/4978 |
| DOI: https://doi.org/10.1523/JNEUROSCI.2672-10.2011 |
Datenträger: | Online-Ressource |
Sprache: | eng |
K10plus-PPN: | 1831146096 |
Verknüpfungen: | → Zeitschrift |
¬A¬ signaling cascade of nuclear calcium-CREB-ATF3 activated by synaptic NMDA receptors defines a gene repression module that protects against extrasynaptic NMDA receptor-induced neuronal cell death and ischemic brain damage / Zhang, Sheng-Jia [VerfasserIn]; March 30, 2011 (Online-Ressource)