Activation of c-Jun N-terminal kinase 1/2 regulated by nitric oxide is associated with neuronal survival in hippocampal neurons in a rat model of ischemia

作者：Zeng Xian-wei; Li Ming-wei; Pan Jing; Ji Tai-ling; Yang Bin; Zhang Bo; Wang Xiao-qiang^*

来源：Chinese Medical Journal, 2011, 124(20): 3367-3372.

DOI：10.3760/cma.j.issn.0366-6999.2011.20.029

• cerebral ischemia
• c-Jun N-terminal kinase 1/2
• nitric oxide
• 7-nitroindazole
• 2-amino-5,6-dihydro-methylthiazine

Background C-Jun N-terminal kinase (JNK) signaling pathway plays a critical role in cerebral ischemia. Although the mechanistic basis for this activation of JNK1/2 is uncertain, oxidative stress may play a role. The purpose of this study was to investigate whether the activation of JNK1/2 is associated with the production of endogenous nitric oxide (NO). @@@ Methods Ischemia and reperfusion (I/R) was induced by cerebral four-vessel occlusion. Sprague-Dawley (SD) rats were divided into 6 groups: sham group, I/R group, neuronal nitric oxide synthase (nNOS) inhibitor (7-nitroindazole, 7-NI) given group, inducible nitric oxide synthase (iNOS) inhibitor (2-amino-5,6-dihydro-methylthiazine, AMT) given group, sodium chloride control group, and 1% dimethyl sulfoxide (DMSO) control group. The levels of protein expression and phospho-JNK1/2 were detected by Western blotting and the survival hippocampus neurons in CA1 zone were observed by cresyl violet staining. @@@ Results The study illustrated two peaks of JNK1/2 activation occurred at 30 minutes and 3 days during reperfusion. 7-NI inhibited JNK1/2 activation during the early reperfusion, whereas AMT preferably attenuated JNK1/2 activation during the later reperfusion. Administration of 7-NI and AMT can decrease I/R-induced neuronal loss in hippocampal CA1 region. @@@ Conclusion JNK1/2 activation is associated with endogenous NO in response to ischemic insult. Chin Med J2011;124(20):3367-3372

• 出版日期2011-10-20
• 单位上海交通大学; 复旦大学; 上海市闵行区中心医院; 潍坊医学院