Pei Dong-Sheng, Song Yuan-Jian, Yu Hong-Min, Hu Wei-Wei, Du Yang, Zhang Guang-Yi
Research Center for Biochemistry and Molecular Biology, The Jiangsu Key Laboratory of Brain Disease Bioinformation, Xuzhou Medical College, Xuzhou, China.
J Neurochem. 2008 Aug;106(4):1952-63. doi: 10.1111/j.1471-4159.2008.05531.x. Epub 2008 Jun 28.
Nitric oxide (NO), synthesized from l-arginine by NO synthases, is a small endogenous free radical with multiple functions. The c-Jun N-terminal kinase (JNK) signaling pathway plays a critical role in mediating apoptosis in cerebral ischemia and reperfusion. In this study, we found that the NO donor sodium nitroprusside (SNP) can decrease the damage of hippocampal neurons induced by cerebral ischemia and reperfusion. Our current study demonstrates that SNP can suppress the phosphorylation of JNK3 by suppressing the increased S-nitrosylation of JNK3 induced by cerebral ischemia and reperfusion. In contrast, dithiothreitol reversed the effect of SNP on S-nitrosylation of JNK3. Furthermore, the inhibitor of nNOS (7-NI) and the inhibitor of iNOS (AMT) can decrease JNK3 phosphorylation through decreasing S-nitrosylation of JNK3. Our data suggest that endogenous NO synthesized by NO synthases can increase JNK3 phosphorylation by means of S-nitrosylation during global ischemia/reperfusion in rat hippocampus. However, the exogenous NO (SNP) can reverse the effect of endogenous NO by inhibiting S-nitrosylation of JNK3. Together, these results suggest that the exogenous NO may provide a new clue for stroke therapy.
一氧化氮（NO）由一氧化氮合酶从L-精氨酸合成，是一种具有多种功能的内源性小自由基。c-Jun氨基末端激酶（JNK）信号通路在介导脑缺血再灌注中的细胞凋亡中起关键作用。在本研究中，我们发现NO供体硝普钠（SNP）可以减少脑缺血再灌注诱导的海马神经元损伤。我们目前的研究表明，SNP可以通过抑制脑缺血再灌注诱导的JNK3 S-亚硝基化增加来抑制JNK3的磷酸化。相反，二硫苏糖醇逆转了SNP对JNK3 S-亚硝基化的作用。此外，nNOS抑制剂（7-NI）和iNOS抑制剂（AMT）可以通过降低JNK3的S-亚硝基化来降低JNK3磷酸化。我们的数据表明，在大鼠海马全脑缺血/再灌注期间，一氧化氮合酶合成的内源性NO可以通过S-亚硝基化增加JNK3磷酸化。然而，外源性NO（SNP）可以通过抑制JNK3的S-亚硝基化来逆转内源性NO的作用。总之，这些结果表明外源性NO可能为中风治疗提供新的线索。
