Effect of berberine on cell cycle arrest and cell survival during cerebral ischemia and reperfusion and correlations with p53/cyclin D1 and PI3K/Akt
Effect of berberine on cell cycle arrest and cell survival during cerebral ischemia and reperfusion and correlations with p53/cyclin D1 and PI3K/Akt
复制标题
小檗碱对脑缺血再灌注期间细胞周期阻滞和细胞存活的影响及其与 p53/cyclin D1 和 PI3K/Akt 的相关性
DOI：
10.1016/j.ejphar.2013.02.041
复制
发表时间：
2013-05-15
影响因子：
5
通讯作者：
Du, Li-Jun
中科院分区：
文献类型：
--
作者：
Chai, Yu-Shuang;Hu, Jun;Du, Li-Jun
黄连素是一种具有多种药理活性的天然药物。在本研究中，我们从细胞周期停滞和细胞存活两个方面探讨了黄连素对脑缺血损伤的影响。采用PC12细胞和原代神经元缺氧缺糖、小鼠颈动脉结扎作为体内外脑缺血模型。结果发现，黄连素对缺血时细胞周期的抑制作用是通过降低P53和细胞周期蛋白D1，增加Bad的磷酸化(p-Bad的高表达和p-Bad/Bad的比值)和减少caspase3的裂解来实现的。同时，黄连素在再灌注过程中激活了PI3K/Akt通路，尤其是Akt的磷酸化，从而促进了细胞的存活。黄连素的神经保护作用在丝裂原活化蛋白/细胞外信号调节蛋白(MEK)抑制剂存在的情况下保持不变，但在PI3K和Akt抑制剂的存在下被抑制。我们证明了黄连素诱导细胞周期停滞和细胞存活以抵抗脑缺血损伤。(C)2013爱思唯尔B.V.保留所有权利。
Berberine acted as a natural medicine with multiple pharmacological activities. In the present study, we examined the effect of berberine against cerebral ischemia damage from cell cycle arrest and cell survival. Oxygen-glucose deprivation of PC12 cells and primary neurons, and carotid artery ligation in mice were used as in vitro and in vivo cerebral ischemia models. We found that the effect of berberine on cell cycle arrest during ischemia was mediated by decreased p53 and cyclin D1, increased phosphorylation of Bad (higher expression of p-Bad and higher ratio of p-Bad to Bad) and decreased cleavage of caspase 3. Meanwhile, berberine activated the PI3K/Akt pathway during the reperfusion, especially the phosphor-activation of Akt, to promote the cell survival. The neural protective effect of berberine was remained in the presence of inhibitor of mitogen-activated protein/extracellular signal-regulated kinase (MEK), but was suppressed by the inhibitors of PI3K and Akt. We demonstrated that berberine induced cell cycle arrest and cell survival to resist cerebral ischemia injury. (C) 2013 Elsevier B.V. All rights reserved.