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Modeling Neuronal Death and Degeneration in Mouse Primary Cerebellar Granule Neurons
Published on: November 6, 2017
c-Jun induction is independent of early growth response factor during cerebellar granule neuron apoptosis
1Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
Abstract:
Early growth response factor 1 (Egr-1) is induced during activity deprivation-dependent apoptosis in cerebellar granule neurons and plays a critical role in neuronal apoptosis. It has been proposed that c-Jun lies downstream of the Egr-dependent proapoptotic signaling cascade in cerebellar granule neurons. However, our data show that neither suppressing Egr activity using a dominant-negative mutant nor specifically silencing Egr-1 using small interfering RNA inhibited the activation and expression of c-Jun after activity deprivation in cerebellar granule neurons. Furthermore, two inhibitors, mithramycin A and chromomycin A3, which repressed transcription by selectively displacing GC-rich DNA-binding transcription factors (including those of the Egr family), did not attenuate the activation and expression of c-Jun during neuronal apoptosis. We conclude that c-Jun induction is independent of Egr during apoptosis induced by activity deprivation in cerebellar granule neurons.
Insights
Early Growth Response Factor 1 (Egr-1) does not regulate c-Jun during cerebellar neuron apoptosis. This study found c-Jun induction is independent of Egr-1 signaling in activity-deprived neurons.
Area of Science:
- Neuroscience
- Molecular Biology
- Cell Biology
Background:
- Early Growth Response Factor 1 (Egr-1) is implicated in activity deprivation-induced apoptosis of cerebellar granule neurons.
- c-Jun has been proposed to be a downstream target of the Egr-dependent proapoptotic pathway.
Purpose of the Study:
- To investigate the relationship between Egr-1 and c-Jun activation during neuronal apoptosis.
- To determine if Egr-1 signaling is required for c-Jun induction in cerebellar granule neurons undergoing apoptosis.
Main Methods:
- Utilized dominant-negative Egr mutants and small interfering RNA (siRNA) to suppress Egr activity.
- Employed transcription inhibitors (mithramycin A, chromomycin A3) that target GC-rich DNA-binding factors.
- Assessed activation and expression of c-Jun following activity deprivation in cerebellar granule neurons.
Main Results:
- Suppression of Egr activity or Egr-1 silencing did not inhibit c-Jun activation or expression after activity deprivation.
- Transcription inhibitors targeting Egr family factors did not attenuate c-Jun activation and expression.
- These findings indicate Egr-1 is not essential for c-Jun induction in this context.
Conclusions:
- c-Jun induction is independent of Egr signaling during apoptosis of cerebellar granule neurons induced by activity deprivation.
- The proposed downstream regulation of c-Jun by Egr-1 in this apoptotic pathway is not supported by these findings.
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