Tian Hui, Zhang Guangyi, Li Hongchun, Zhang Quanguang
Research Center for Biochemistry and Molecular Biology, Xuzhou Medical College, 84 West Huai-hai Road, Xuzhou, Jiangsu 221002, PR China.
Neurosci Res. 2003 Jun;46(2):191-7. doi: 10.1016/s0168-0102(03)00057-9.
c-Jun N-terminal kinase-3 (JNK3), the only neural-specific isoform, may play an important role in excitotoxicity and neuronal injury. To analyze the variation of JNK3 activation, levels of phospho-JNK3 were measured at various time points of ischemia and selected time points of reperfusion, respectively. Our study illustrated that JNK3 was rapidly activated and translocated from cytosol to nucleus during ischemia. During reperfusion, two peaks of JNK3 activation occurred at 30 min and 3 days, respectively. To further define the mechanism of JNK3 activation, antioxidant N-acetylcysteine (NAC), alpha-amino-3-hydroxyl-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate (KA) receptor antagonist 6,7-dinitro-quinoxaline-2,3(1H,4H)-dione (DNQX), N-methyl-D-aspartate (NMDA) receptor antagonist ketamine and L-type voltage-gated Ca(2+) channel (L-VGCC) antagonist nifedipine were given to the rats 20 min prior to ischemia. The results showed that NAC obviously inhibited JNK3 activation during the early reperfusion, whereas DNQX preferably attenuated JNK3 activation during the latter reperfusion. Ketamine and nifedipine had no significant effects on JNK3 activation during reperfusion. Consequently, reactive oxygen species (ROS) and AMPA/KA receptor were closely associated with JNK3 activation following global ischemia.
c-Jun氨基末端激酶3（JNK3）是唯一的神经特异性亚型，可能在兴奋性毒性和神经元损伤中起重要作用。为分析JNK3激活的变化情况，分别在缺血的不同时间点和再灌注的选定时间点测量磷酸化JNK3的水平。我们的研究表明，在缺血期间JNK3迅速被激活并从胞质溶胶转移至细胞核。在再灌注期间，JNK3激活出现两个峰值，分别在30分钟和3天。为进一步明确JNK3激活的机制，在缺血前20分钟给大鼠注射抗氧化剂N-乙酰半胱氨酸（NAC）、α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）/海人藻酸（KA）受体拮抗剂6,7-二硝基喹喔啉-2,3（1H，4H）-二酮（DNQX）、N-甲基-D-天冬氨酸（NMDA）受体拮抗剂氯胺酮和L型电压门控钙通道（L-VGCC）拮抗剂硝苯地平。结果显示，NAC在早期再灌注期间明显抑制JNK3激活，而DNQX在后期再灌注期间更有效地减弱JNK3激活。氯胺酮和硝苯地平在再灌注期间对JNK3激活无显著影响。因此，活性氧（ROS）和AMPA/KA受体与全脑缺血后的JNK3激活密切相关。
