Journal
JOURNAL OF MOLECULAR NEUROSCIENCE
Volume 56, Issue 4, Pages 782-788Publisher
SPRINGERNATURE
DOI: 10.1007/s12031-015-0500-2
Keywords
Hippocampal neurons; AMPK; CREB; SIRT1/miR-134; Dual role
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The hippocampus is vulnerable to damage under conditions of ischemia and hypoxia, causing multiple mental illnesses. cAMP response element-binding protein (CREB) plays a pivotal role in preventing the apoptosis of neurons and many other cells. Here, we found that AMP-activated protein kinase (AMPK) and CREB are oppositely regulated in mouse primary hippocampal neurons impaired by hypoxia-hypoglycemia. AMPK overexpression reduced the CREB level by upregulating SIRT1 and was negatively posttranscriptionally regulated by miR-134, suggesting a negative regulatory role of AMPK in the expression of CREB. Interestingly, the downstream genes of CREB, brain-derived neurotrophic factor (BDNF), and Bcl-2 remained unchanged when CREB was downregulated by AMPK expression. In addition, in AMPK(-/-)primary hippocampal neurons, comparisons between the effect of upregulation and silencing of miR-134 on the expression of CREB, BDNF, and Bcl-2 were made. The results reveal that AMPK is crucial for the activation of CREB via phosphorylation. Therefore, AMPK plays a dual role in the regulation of CREB in mouse primary hippocampal cells: a negative effect on total CREB expression by elevating SIRT1/miR-134 and a positive effect on activity via phosphorylation.
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