Claulansine F promoted the neuronal differentiation of neural stem and progenitor cells through Akt/GSK-3β/β-catenin pathway
| Autor: | Shifeng Chu, Dong-Ming Zhang, Yin-zhong Ma, Hang Liu, Yu-He Yuan, Ju-yang Huang, Nai-Hong Chen, Wei Zuo, Guanhua Du |
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| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Neurogenesis Carbazoles Biology PC12 Cells 03 medical and health sciences Neural Stem Cells Animals Progenitor cell Phosphorylation Protein kinase B beta Catenin Cell Proliferation Pharmacology Glycogen Synthase Kinase 3 beta Kinase Neural stem cell Cell biology Rats Enzyme Activation 030104 developmental biology Catenin Signal transduction Proto-Oncogene Proteins c-akt Signal Transduction |
| Zdroj: | European journal of pharmacology. 786 |
| ISSN: | 1879-0712 |
| Popis: | The persistence of neurogenesis raises the idea that neurons produced by the resident or transplanted neural stem cells could replace the neurons lost from brain injury or neurodegenerative disease. Therefore, compounds or methods for promoting neuronal differentiation become the focus of neurodegenerative disease therapy research. Claulansine F (Clau F), a newly discovered carbazole alkaloid, has been showed to induce neuritogenesis in PC12 cells. Herein, we studied the effect of Clau F on neuronal differentiation of neural stem/progenitor cells (NS/PCs). The current study demonstrated that Clau F initiated neuronal differentiation with a significant increase of TuJ1-positive cells and TuJ1 protein levels. We also found that Clau F promoted the maturity and sustainability of neurons by increasing MAP2-positive cells and MAP2 protein levels. At the same time, Clau F significantly inhibited the proliferation of NS/PCs. The underlying mechanism of Clau F was preliminary explored. Clau F treatment resulted in a profound increase of phosphorylation of Akt and GSK-3β, which led to GSK-3β inhibition and subsequently the nuclear accumulation of β-catenin. Further, the interaction between β-catenin and p300 in the nucleus was enhanced and the transcription of p300/β-catenin responsive genes were increased significantly (c-jun, fra-1) by Clau F. Importantly, the positive effect of Clau F on neuronal differentiation was abolished by Akti-1/2, a specific inhibitor of Akt-1/2 kinase, which indicated the involvement of Akt/GSK-3β in Clau F-mediated neuronal differentiation. In conclusion, these data suggested that Clau F promoted neuronal differentiation through Akt/GSK-3β/β-catenin signaling pathway in NS/PCs. |
| Databáze: | OpenAIRE |
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