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Promoting effects of isobavachin on neurogenesis of mouse embryonic stem cells were associated with protein prenylation

  
@article{APS6904,
	author = {Dan-yin Wang and Yu-zhe Hu and Si-si Kong and Yong-ping Yu and Dan-yan Zhu and Yi-jia Lou},
	title = {Promoting effects of isobavachin on neurogenesis of mouse embryonic stem cells were associated with protein prenylation},
	journal = {Acta Pharmacologica Sinica},
	volume = {32},
	number = {4},
	year = {2016},
	keywords = {},
	abstract = {Aim:  Some small molecules can induce mouse embryonic stem (ES) cells to differentiate into neuronal cells. Here, we explored the effect of isobavachin (IBA), a compound with a prenyl group at position 8 of ring A, on promoting neuronal differentiation and the potential role of its protein prenylation.
Methods:  The hanging drop method was employed for embryonic body (EB) formation to mimic embryo development in vivo. The EBs were treated with IBA at a final concentration of 10−7 mol/L from EB stage (d 4) to d 8+10. Geranylgeranyltransferase I inhibitor GGTI-298 was subsequently used to disrupt protein prenylation. Neuronal subtypes, including neurons and astrocytes, were observed by fluorescence microscopy. Gene and protein expression levels were detected using RT-PCR and Western blot analysis, respectively.
Results:  With IBA treatment, nestin was highly expressed in the neural progenitors generated from EBs (d 4, d 8+0). EBs then further differentiated into neurons (marked by β-tubulin III) and astrocytes (marked by GFAP), which were both up-regulated in a time-dependent manner on d 8+5 and d 8+10. Co-treatment with GGTI-298 selectively abolished the IBA-induced neuronal differentiation. Moreover, in the MAPK pathway, p38 and JNK phosphorylation were down-regulated, while ERK phosphorylation was up-regulated after IBA treatment at different neuronal differentiation passages.
Conclusion:  IBA can facilitate mouse ES cells differentiating into neuronal cells. The mechanism involved protein prenylation and, subsequently, phos-ERK activation and the phos-p38 off pathway.},
	issn = {1745-7254},	url = {http://www.chinaphar.com/article/view/6904}
}