Activation of T-LAK-cell-originated protein kinase contribute to the anti-oxidative function against focal cerebral ischemia-reperfusion
Activation of T-LAK-cell-originated protein kinase contribute to the anti-oxidative function against focal cerebral ischemia-reperfusion
复制标题
T-LAK细胞源性蛋白激酶的激活有助于抗局灶性脑缺血再灌注的抗氧化功能
DOI：
10.1016/j.ijdevneu.2015.04.277
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发表时间：
2015-12
影响因子：
1.8
通讯作者：
Yumin Luo
中科院分区：
文献类型：
--
作者：
Xiangrong Liu;Liu Ping;Xunming Ji;Yumin Luo
方法和结果为了阐明其功能，TOPK 在 PC12 神经元细胞中过表达，蛋白质印迹显示抗氧化蛋白过氧化还原蛋白 1 (Prx-1)、Prx-2、血红素加氧酶 1 (HO-1) 和 MnSOD 水平升高，总 SOD 活性升高，这与 H 2 O 2 刺激后过氧化产物 MDA 和 3-硝基酪氨酸的抑制作用一致。同样，暴露于 H 2 O 2 后，TOPK 过表达会增加 PC12 细胞中的细胞活力并减少 Caspase-3 和 Caspase-12 的表达。此外，TOPK 过表达会增加 p-ERK 水平，并且通过阻断 PC12 细胞中的 ERK 通路来消除 TOPK 提供的抗氧化保护。在体内，脑室内注射TOPK过表达载体可减少tMCAO后的梗塞体积和神经元凋亡，增加总SOD活性并减少皮质中ROS的产生。结论总的来说，这些数据表明，激活TOPK部分通过激活ERK通路发挥抗氧化作用，从而对局灶性脑缺血再灌注损伤具有神经保护作用。
Methods and resultsTo clarify its function, TOPK was overexpressed in PC12 neuronal cells, western blot displays elevated levels of antioxidative proteins peroxiredoxin 1 (Prx-1), Prx-2, heme oxygenase 1 (HO-1) and MnSOD, along with the activity of total SOD, which is in line with inhibition of peroxidation product MDA and 3-Nitrotyrosine upon H 2 O 2 stimulation. As well, TOPK overexpression increased cell viability and reduced expression of Caspase-3 and Caspase-12 in PC12 cells upon H 2 O 2 exposure. Furthermore, p-ERK level was increased by TOPK overexpression, and antioxidative protection afforded by TOPK was abolished by blocking ERK pathway in PC12 cells. In vivo, intracerebroventricular injection of TOPK overexpression vector reduced the infarct volume and neuronal apoptosis after tMCAO, increased total SOD activity and decreased ROS production in the cortex.ConclusionCollectively, these data reveal that activating TOPK confers neuroprotection against focal cerebral ischemia reperfusion injury by its antioxidative effect partly through activating ERK pathway.