Hypothermia blacks β-catenin degradation after focal ischemia in rats
Hypothermia blacks β-catenin degradation after focal ischemia in rats
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DOI：
10.1016/j.brainres.2008.01.007
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发表时间：
2008-03-10
期刊：
影响因子：
2.9
通讯作者：
Zhao, Heng
中科院分区：
文献类型：
--
作者：
Zhang, Hanfeng;Ren, Chuancheng;Zhao, Heng
去磷酸化和激活的糖原合酶激酶 (GSK) 3 beta 使 β-连环蛋白过度磷酸化，导致其泛素蛋白酶体介导的降解。 β-连环蛋白敲低增加，而 β-连环蛋白过度表达可防止体外神经元死亡；此外，阿尔茨海默病患者大脑中β-连环蛋白的蛋白质水平也会降低。然而，β-连环蛋白降解是否与中风引起的脑损伤有关尚不清楚。在这里，我们研究了 GSK 3 和 β-连环蛋白的活性，以及中度低温（30 摄氏度）对大鼠局灶性缺血后这些活性的保护作用。 Western blot结果显示，常温（37℃）大脑中GSK 3β在中风后5和24小时发生去磷酸化；低温增强了 GSK 3 β 去磷酸化。因为体温过低。减少梗塞，但这些结果与之前的研究相矛盾，之前的研究表明 GSK 3 去磷酸化会加剧神经元死亡。然而，低温阻止了总 GSK 3 β 蛋白的降解。与常温大鼠中的 GSK 3 活性相对应，缺血半暗带和核心中的 β-catenin 磷酸化在 5 小时内短暂增加，并且常温中风后 -catenin 的总蛋白水平下降。低温不会抑制β-连环蛋白磷酸化，但会阻止缺血半暗带中的β-连环蛋白降解。总之，中低温可以稳定β-连环蛋白，这可能有助于中低温的保护作用。 (c) 2008 Elsevier B.V. 保留所有权利。
Dephosphorylated and activated glycogen synthase kinase (GSK) 3 beta hyperphosphorylates beta-catenin, leading to its ubiquitin-proteosome-mediated degradation. beta-catenin-knockdown increases while beta-catenin overexpression prevents neuronal death in vitro; in addition, protein levels of beta-catenin are reduced in the brain of Alzheimer's patients. However, whether beta-catenin degradation is involved in stroke-induced brain injury is unknown. Here we studied activities of GSK 3 and beta-catenin, and the protective effect of moderate hypothermia (30 degrees C) on these activities after focal ischemia in rats. The results of Western blot showed that GSK 3 beta was dephosphorylated at 5 and 24 h after stroke in the normothermic (37 degrees C) brain; hypothermia augmented GSK 3 beta dephosphorylation. Because hypothermia. reduces infarction, these results contradict with previous studies showing that GSK 3 dephosphorylation worsens neuronal death. Nevertheless, hypothermia blocked degradation of total GSK 3 beta protein. Corresponding to GSK 3 activity in normothermic rats, beta-catenin phosphorylation transiently increased at 5 h in both the ischemic penumbra and core, and the total protein level of-catenin degraded after normothermic stroke. Hypothermia did not inhibit beta-catenin phosphorylation, but it blocked beta-catenin degradation in the ischemic penumbra. In conclusion, moderate hypothermia can stabilize beta-catenin, which may contribute to the protective effect of moderate hypothermia. (c) 2008 Elsevier B.V. All rights reserved.