Mediation by a CREB Family Transcription Factor of NGF-Dependent Survival of Sympathetic Neurons

Riccio, Antonella; Ahn, Sang‐Hyeon; Davenport, Christopher M.; Blendy, Julie A.; Ginty, David D.

doi:10.1126/science.286.5448.2358

Cited by 736 publications

(585 citation statements)

References 21 publications

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“…NGF has been reported to activate the Bcl-2 promoter through MEK/MAPK in PC12 cells, 37 while NGF induces Bcl-2 expression in sympathetic neurons through cyclic adenosine monophosphate (cAMP) response element binding protein (CREB)-dependent transcriptional mechanisms. 38 Here, we demonstrate that Cdk5-mediated Bcl-2 upregulation occurs through the ERK1/2 pathway during neuronal differentiation and ERK1/2-mediated Bcl-2 expression contributes to Cdk5-mediated neuronal survival. Clearly, further investigation of the interactions between Cdk5-mediated signaling pathways and apoptotic pathways will shed more light on the molecular mechanisms that control neuronal death and survival during neuronal differentiation and disease.…”

Section: Discussionmentioning

confidence: 62%

Cyclin-dependent kinase-5 prevents neuronal apoptosis through ERK-mediated upregulation of Bcl-2

Wang

Song

et al. 2005

Cell Death Differ

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Cyclin-dependent kinase-5 (Cdk5) is required for neuronal survival, but its targets in the apoptotic pathways remain unknown. Here, we show that Cdk5 kinase activity prevents neuronal apoptosis through the upregulation of Bcl-2. Treatment of SH-SY5Y cells with retinoid acid (RA) and brain-derived neurotrophic factor (BDNF) generates differentiated neuron-like cells. DNA damage triggers apoptosis in the undifferentiated cells through mitochondrial pathway; however, RA/BDNF treatment results in Bcl-2 upregulation and inhibition of the mitochondrial pathway in the differentiated cells. RA/BDNF treatment activates Cdk5-mediated PI3K/Akt and ERK pathways. Inhibition of Cdk5 inhibits PI3K/ Akt and ERK phosphorylation and Bcl-2 expression, and thus sensitizes the differentiated cells to DNA-damage. Inhibition of ERK, but not PI3K/Akt, abrogates Cdk5-medidated Bcl-2 upregulation and the protection of the differentiated cells. This study suggests that ERK-mediated Bcl-2 upregulation contributes to BDNF-induced Cdk5-mediated neuronal survival.

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Section: Discussionmentioning

confidence: 62%

Cyclin-dependent kinase-5 prevents neuronal apoptosis through ERK-mediated upregulation of Bcl-2

Wang

Song

et al. 2005

Cell Death Differ

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“…In vitro studies have shown that the Bcl-xl gene promoter is regulated by NF-kB and its expression is regulated by the MAPK signaling pathway (Marinari et al, 2004;Yu et al, 2005) The Bcl-2 promoter contains a CRE that mediates its responsivity to the transcription factor (CREB) (Bonni et al, 1999;Riccio et al, 1999). Withdrawal of trophic support as well as an inhibition of CREB transcription triggers apoptosis in neurons.…”

Section: Discussionmentioning

confidence: 99%

“…Exposure to stress downregulates BDNF levels in the amygdala, hippocampus, and cortex (Pizarro et al, 2004;Smith et al, 1995). The known signaling pathways that mediate the effects of the neurotrophic factors on Bcl-2 and Bcl-xl are the Rsk/MAP pathway, JNK pathway, and the PI-3K/AKT pathway (Manji and Duman, 2001;Bonni et al, 1999;Riccio et al, 1999). Stressors such as forced-swim and restraint stress induce activation of the MKK4-JNK signaling pathway in the hippocampus, amygdala, and hypothalamus (Liu et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

Repeated Unpredictable Stress and Antidepressants Differentially Regulate Expression of the Bcl-2 Family of Apoptotic Genes in Rat Cortical, Hippocampal, and Limbic Brain Structures

Kosten

Galloway

Duman

et al. 2007

Neuropsychopharmacol

144

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Apoptosis has been proposed as a contributing cellular mechanism to the structural alterations that have been observed in stress-related mood disorders. Antidepressants, on the other hand, are hypothesized to exert trophic and/or neuroprotective actions. The present study examined the regulation of the major antiapoptotic (Bcl-2, Bcl-xl) and proapoptotic (Bax) genes by repeated unpredictable stress (an animal model of depression) and antidepressant treatments (ADT). In adult rats, exposure to unpredictable stress reduced Bcl-2 mRNA levels in the central nucleus of the amygdala (CeA), cingulate (Cg), and frontal (Fr) cortices. Bcl-xl mRNA was significantly decreased in hippocampal subfields. In contrast, chronic administration of clinically effective antidepressants from four different classes, ie fluoxetine, reboxetine, tranylcypromine, and electroconvulsive seizures (ECS) upregulated Bcl-2 mRNA expression in the Cg, Fr, and CeA. Reboxetine, tranylcypromine, and ECS selectively increased Bcl-xl, but not Bcl-2 mRNA expression in the hippocampus. Chemical ADT but not ECS, robustly enhanced Bcl-2 expression in the medial amygdaloid nucleus and ventromedial hypothalamus. Fluoxetine did not influence Bcl-xl expression in the hippocampus, but it was the only ADT that decreased Bax expression in this region. In the CeA, again in direct contrast to the stress effects, exposure to all classes of ADTs significantly increased Bcl-2 mRNA. The selective regulation of Bcl-xl and Bax in hippocampal subfields and of Bcl-2 in the Cg cortex, amygdala, and hypothalamus suggests that these cellular adaptations contribute to the long-term neural plastic adaptations to stress and ADTs in cortical, hypothalamic, and limbic brain structures.

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“…Such an effect could significantly alter hippocampal function. Several studies have shown that CREB-mediated gene expression is important for the survival of a variety of neuronal types (Bonni et al, 1999;Riccio et al, 1999;Walton et al, 1999). In addition, CREB induced gene expression plays an important role in learning, memory and synaptic plasticity (Bito et al, 1996;Hu et al, 1999).…”

Section: Discussionmentioning

confidence: 99%

Chronic CXCL10 alters the level of activated ERK1/2 and transcriptional factors CREB and NF-κB in hippocampal neuronal cell culture

Bajova

Nelson

Gruol

2008

Journal of Neuroimmunology

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Signal transduction pathways may be important targets of chemokines during neuroinflammation. In the current study, Western blot analyses show that in rat hippocampal neuronal/glial cell cultures chronic CXCL10 increases the level of protein for ERK1/2 as well as for the transcriptional factors CREB and NF-κB. Bcl-2, an anti-apoptotic protein whose expression can be regulated by a pathway involving ERK1/2, CREB and NF-κB, was also increased in the CXCL10 treated cultures. These results implicate a role for ERK1/2, CREB and NF-κB in effects of CXCL10 on hippocampal cells and suggest that chronic CXCL10 may have a protective role during certain neuroinflammatory conditions.

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Mediation by a CREB Family Transcription Factor of NGF-Dependent Survival of Sympathetic Neurons

Cited by 736 publications

References 21 publications

Cyclin-dependent kinase-5 prevents neuronal apoptosis through ERK-mediated upregulation of Bcl-2

Cyclin-dependent kinase-5 prevents neuronal apoptosis through ERK-mediated upregulation of Bcl-2

Repeated Unpredictable Stress and Antidepressants Differentially Regulate Expression of the Bcl-2 Family of Apoptotic Genes in Rat Cortical, Hippocampal, and Limbic Brain Structures

Chronic CXCL10 alters the level of activated ERK1/2 and transcriptional factors CREB and NF-κB in hippocampal neuronal cell culture

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