薯蓣皂素在神經幹細胞中可促進神經分化是透過調節AKT活性和細胞週期

Diosgenin Promotes Neuronal Differentiation by Regulating AKT Activity and Cell Cycle in Neural Stem Cells

徐芊華(Chien-Hua Hsu)

指導教授 ： 鄭鈞文

中山醫學大學/醫學院/生化暨生物科技研究所/碩士(2009年)

https://doi.org/10.6834/CSMU.2009.00076

摘要

神經幹細胞是一種具有自我更新能力，且有分化能力之原母細胞，然而在調控神經幹細胞的分化上，其相關機制尚未明瞭。先前在我們的研究中發現薯蕷皂素 (Diosgenin) 可促進神經幹細胞的分化，然而，尚未釐清其調節機制。有鑑於此，本研究的目的將探討Diosgenin如何誘導神經幹細胞的分化。我們從14-15天Sprague-Dawley大白鼠的胚胎中獲得神經幹細胞並以神經球(neurospheres)方式進行培養。以Diosgenin 處理神經前驅細胞後，它會誘導神經幹細胞分化，此一現象可以藉由神經幹細胞早期分化的特有蛋白TUJ-1表現量上升而得到驗證。另外，實驗結果透露兩個重要訊息： (1) Diosgenin 處理分化早期的神經前驅細胞，是經由cyclin-dependent kinase inhibitor p27 kip1的表現量提升，調控細胞週期蛋白質 cyclin D1和 cdk4表現量下降，使細胞週期停滯在G1時期。(2) Diosgenin 處理下，會增加神經前驅細胞之 Akt磷酸化。 綜合而言， Diosgenin是透過調控細胞週期和 Akt 的磷酸化來影響神經幹細胞的分化。

關鍵字

薯蓣皂素 ； 神經幹細胞

並列摘要

Neural stem cells (NSCs) are defined as cells with self-renewal and multi-potential capabilities. However, knowledge of the molecular mechanism underlying differentiation of NSCs is still inconclusive. The aim of this study is to examine the effect of diosgenin on NSCs. Diosgenin, a steroidal sapogenin is extracted from the root of wild yam (Dioscorea villosa). NSCs were collected from 14-day-old rat embryos which are propagated as neurospheres. Our results showed that increased expression of the TUJ1 protein in NSCs was observed in the presence of 2 μM diosgenin. Expression level of the cyclin-dependent kinase inhibitor p27kip1 is significantly higher in diosgenin-treated NSCs than that detected in the control. After the treatment with diosgenin, NSCs were arrested in the G1 phase of cell cycle, associating with the reduced expressions of the cyclin D1 and cdk4. In addition, diosgenin increased Akt phosphorylation. In conclusion, our results provide the support that the mechanism of neuronal differentiation through AKT phosphorylation by diosgenin is involved in regulating the expression of cyclin D1/Cdk4 complex in NSCs.

並列關鍵字

Diosgenin ； Neural Stem Cells

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