XAV939, a Small Molecular Inhibitor, Provides Neuroprotective Effects on Oligodentrocytes
XAV939, a Small Molecular Inhibitor, Provides Neuroprotective Effects on Oligodentrocytes
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DOI：
10.1002/jnr.23415
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发表时间：
2014-10-01
影响因子：
4.2
通讯作者：
Liu, Chun-Feng
中科院分区：
文献类型：
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作者：
Chen, Jing;Li, Jizhen;Liu, Chun-Feng
白质束由轴突和髓鞘少突胶质细胞组成。少突胶质细胞是中枢神经系统中的髓鞘形成细胞，可形成髓鞘和跳跃神经传导。成人和新生儿的脑白质极易受到缺血性损伤。新生儿大脑白质损伤会导致脑瘫和认知障碍。在这项研究中，我们发现 XAV939（一种小分子抑制剂，通过稳定轴蛋白刺激 β-连环蛋白降解）以浓度依赖性方式防止少突胶质细胞系 OLN-93 细胞中血清和葡萄糖剥夺（SGD）诱导的细胞死亡。我们进一步表明，XAV939 降低了 SGD 诱导的 OLN-93 细胞中 caspase-3 和 caspase-8 的水平，并增加了磷酸化 Akt 的表达。我们的数据表明 XAV939 可以预防新生儿缺氧/缺血性损伤。总之，我们的结果表明，XAV939 通过其抗凋亡活性以及新生儿缺氧/缺血性损伤中少突胶质细胞和神经元的损失，对 OLN-93 细胞中 SGD 诱导的损伤具有神经保护作用。 (C) 2014 年 Wiley 期刊公司。
White matter tracts are composed of axons and myelinating oligodendrocytes. Oligodendrocytes are the myelinating cells in the central nervous system that allow formation of myelin and saltatory nerve conduction. Cerebral white matter is highly vulnerable to ischemic injury in adults and neonates. White matter injury in newborn brains results in cerebral palsy and cognitive disability. In this study, we found that XAV939, a small-molecular inhibitor that stimulated beta-catenin degradation by stabilizing axin, protected against serum and glucose deprivation (SGD)-induced cell death in oligodentrocyte cell line OLN-93 cells in a concentration-dependent manner. We further showed that XAV939 reduced caspase-3 and caspase-8 levels and increased the expression of phosphorylated Akt in SGD-induced OLN-93 cells. Our data demonstrate that XAV939 protects against neonatal hypoxic/ ischemic injury. In summary, our results demonstrate that XAV939 confers neuroprotection against SGD-induced injury in OLN-93 cells via its antiapoptotic activity and the loss of oligodendrocytes and neurons in neonatal hypoxic/ischemic injury. (C) 2014 Wiley Periodicals, Inc.