Dataset Information

Glucocorticoid receptor and myocyte enhancer factor 2 cooperate to regulate the expression of c-JUN in a neuronal context.

ABSTRACT: The glucocorticoid receptor (GR) and myocyte enhancer factor 2 (MEF2) are transcription factors involved in neuronal plasticity. c-JUN, a target gene of GR and MEF2, plays a role in regulating both synaptic strength and synapse number. The aim of this study was to investigate the nature of this dual regulation of c-JUN by GR and MEF2 in a neuronal context. First, we showed that GR mediates the dexamethasone-induced suppression of c-JUN mRNA expression. Next, we observed that GR activation resulted in an increase in phosphorylation of MEF2, a post-translational modification known to change MEF2 from a transcriptional enhancer to a repressor. In addition, we observed an enhanced binding of MEF2 to genomic sites directly upstream of the c-JUN gene upon GR activation. Finally, in primary hippocampal neuronal cultures, knockdown of MEF2 not only reduced c-JUN expression levels but abolished GR regulation of c-JUN expression. This suggests that MEF2 is necessary for GR regulation of c-JUN. In conclusion, for the first time, we show that activated GR requires MEF2 to regulate c-JUN. At the same time, GR influences MEF2 activity and DNA binding. These results give novel insight into the molecular interplay of GR and MEF2 in the control of genes important for neuronal plasticity.

SUBMITTER: Speksnijder N

PROVIDER: S-EPMC3413818 | biostudies-literature | 2012 Sep

REPOSITORIES: biostudies-literature

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Glucocorticoid receptor and myocyte enhancer factor 2 cooperate to regulate the expression of c-JUN in a neuronal context.

Speksnijder Niels N Christensen Kenneth V KV Didriksen Michael M De Kloet E Ronald ER Datson Nicole A NA

Journal of molecular neuroscience : MN 20120524 1

The glucocorticoid receptor (GR) and myocyte enhancer factor 2 (MEF2) are transcription factors involved in neuronal plasticity. c-JUN, a target gene of GR and MEF2, plays a role in regulating both synaptic strength and synapse number. The aim of this study was to investigate the nature of this dual regulation of c-JUN by GR and MEF2 in a neuronal context. First, we showed that GR mediates the dexamethasone-induced suppression of c-JUN mRNA expression. Next, we observed that GR activation result ...[more]

PMID: 22622902

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Project description:Premature ventricular contractions (PVCs) are common in the general population, and frequent PVCs may result in the poor quality of life or even the damage of cardiac function. We examined the efficacy and safety of a traditional Chinese medicine Wenxin Keli for the treatment of frequent PVCs among a relatively large Chinese cohort.We performed a randomized, double-blind, placebo-controlled, parallel-group, multicenter trial. A total of 1200 eligible participants were randomly assigned in a ratio of 1:1 to receive Wenxin Keli or the placebo for 4 weeks. The primary and secondary endpoint was the change of PVC numbers and PVC-related symptoms after a 4-week treatment compared with baseline, respectively. In addition, vital signs, laboratory values, and electrocardiographic parameters were assessed in a safety analysis.At the initial evaluation, no significant differences in the baseline characteristics were observed between the Wenxin Keli group and the placebo group. A smaller number of PVCs was observed after the 4-week treatment than at baseline, in both the Wenxin Keli group (5686 ± 5940 vs. 15,138 ± 7597 beats/d, P < 0.001) and the placebo group (10,592 ± 8009 vs. 14,529 ± 5929 beats/d, P < 0.001); moreover, the Wenxin Keli group demonstrated a significantly greater reduction in the frequency of PVCs than the placebo group (P < 0.001). In a full analysis set, patients in the Wenxin Keli group exhibited significantly higher total effective responses in the reduction of PVCs compared to those in the placebo group (83.8% vs. 43.5%,P < 0.001). The per-protocol analysis yielded similar results (83.0% vs. 39.3%,P < 0.001). Treatment with Wenxin Keli also demonstrated superior performance compared to the placebo with respect to PVC-related symptoms. No severe adverse effects attributable to Wenxin Keli were reported.Wenxin Keli treatment effectively reduced the overall number of PVCs and alleviated PVC-related symptoms in patients without structural heart diseases and had no severe side effects.

Dataset Information

Glucocorticoid receptor and myocyte enhancer factor 2 cooperate to regulate the expression of c-JUN in a neuronal context.

Publications

Glucocorticoid receptor and myocyte enhancer factor 2 cooperate to regulate the expression of c-JUN in a neuronal context.

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