Involvement of oxidative stress in the rapid Akt1 regulating a JNK scaffold during ischemia in rat hippocampus
Involvement of oxidative stress in the rapid Akt1 regulating a JNK scaffold during ischemia in rat hippocampus
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DOI：
10.1016/j.neulet.2005.08.057
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发表时间：
2006-01
影响因子：
2.5
通讯作者：
Jing-kun Pan;D. Pei;Xiao-hui Yin;Liang Hui;Guang-yi Zhang
中科院分区：
文献类型：
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作者：
Jing-kun Pan;D. Pei;Xiao-hui Yin;Liang Hui;Guang-yi Zhang
已有文献表明，Akt1和JNK通路的激活参与了脑缺血时神经元细胞的死亡。在这项研究中，我们描述了Akt1和JNK相互作用蛋白1 （JIP-1）之间的一种新的相互作用。我们首先在缺血的不同时间点检测了海马中Akt1和JIP-1的相互作用。在基础状态下，JIP-1与Akt1、MLK3结合最多，与JNK3结合最少。缺血刺激降低了Akt1-JIP-1的相互作用，同时增加了JIP-1与JNK3的关联。而MLK3与JIP-1的结合减少，类似于缺血时Akt1-JIP-1的相互作用。这些结果表明，Akt1与JIP-1的相互作用通过降低JIP-1与特定JNK通路激酶的结合，抑制了JIP-1介导的JNK活性增强。Akt1结合JIP-1作为阻止JNK激活的调控门，在缺血损伤条件下打开。抗氧化剂n -乙酰半胱氨酸（NAC）可明显影响缺血15min时海马组织中MLK3、JNK3和Akt1与JIP-1的结合水平和JNK3的激活。结果提示，在脑缺血时，Akt1通过调控JNK支架进而调控JNK活化与活性氧（ROS）密切相关。
It has been well documented that the activation of Akt1 and JNK pathways are involved in the neuronal cell death in cerebral ischemia. In this study, we describe a novel interaction between Akt1 and JNK interacting protein 1 (JIP-1). We first detected the interaction of Akt1 and JIP-1 in hippocampus at various time points of ischemia. In the basal state, JIP-1 bind to Akt1, MLK3 at maximum while JIP-1 binds to JNK3 at minimum. Ischemia stimulus decreased the Akt1–JIP-1 interaction and concomitantly increased association between JIP-1 and JNK3. While MLK3 binding to JIP-1 decreased, similar to Akt1–JIP-1 interaction during ischemia. These results indicated that Akt1 interaction with JIP-1 inhibited JIP-1-mediated potentiation of JNK activity by decreasing JIP-1 binding to specific JNK pathway kinases. Akt1 binding to JIP-1 acts as a regulatory gate preventing JNK activation, which is opened under conditions ischemia injury. Administration of antioxidant N-acetylcysteine (NAC) can obviously affected the level of MLK3, JNK3 and Akt1 binding to JIP-1 and JNK3 activation in the hippocampus at 15min ischemia. The findings suggest that Akt1 regulating JNK scaffold and then regulating JNK activation were closely associated with reactive oxygen species (ROS) during cerebral ischemia.