Inhibition of glycogen synthase kinase 3β is involved in the resistance to oxidative stress in neuronal HT22 cells
Inhibition of glycogen synthase kinase 3β is involved in the resistance to oxidative stress in neuronal HT22 cells
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DOI：
10.1016/j.brainres.2004.01.037
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发表时间：
2004-04-16
期刊：
影响因子：
2.9
通讯作者：
Behl, C
中科院分区：
文献类型：
--
作者：
Schäfer, M;Goodenough, S;Behl, C
氧化应激涉及多种神经退行性疾病，包括阿尔茨海默病、帕金森病和缺血性再灌注损伤（中风）。我们建立了小鼠海马神经细胞系HT22的克隆，分别对氧化应激剂谷氨酸和过氧化氢具有抗性。这些细胞克隆显示出对其他氧化应激源的相互交叉抗性，但对本质上非氧化性神经毒素却没有。我们发现，在两个耐药克隆中，磷酸化的、无活性的糖原合成酶激酶（GSK） 3β的数量都升高了。在敏感的亲代神经细胞中，用氯化锂对gsk -3 β进行药理学抑制可导致gsk -3 β对谷氨酸和过氧化氢的耐受性增加，这表明gsk -3 β参与控制这些细胞的氧化应激抗性。(C) 2004 Elsevier B.V.版权所有
Oxidative stress is involved in several neurodegenerative diseases including Alzheimer's disease, Parkinson's disease and ischemic reperfusion injury (stroke). We have established clones of the murine hippocampal neuronal cell line HT22, which are resistant to the oxidative stress-causing agents glutamate and hydrogen peroxide, respectively. These cell clones show a mutual cross-resistance to other oxidative stressors, but not to essentially non-oxidative neurotoxins. We have discovered that the amount of phosphorylated, inactive glycogen synthase kinase (GSK) 3beta is elevated in both resistant clones. Pharmacological inhibition of GSK-3beta with lithium chloride in the sensitive parental neuronal cells results in an increased tolerance to glutamate and hydrogen peroxide, suggesting that GSK-3beta is involved in the control of oxidative stress resistance in these cells. (C) 2004 Elsevier B.V. All rights reserved.