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 / 中华医学杂志(英文版)

ABSTRACT

<p><b>BACKGROUND</b>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).</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSION</b>JNK1/2 activation is associated with endogenous NO in response to ischemic insult.</p>