Chen Ming, Sun Hong-Yu, Li Shu-Ji, Das Manas, Kong Ji-Ming, Gao Tian-Ming
Department of Anatomy and Neurobiology, Southern Medical University, Guangzhou, China.
Neurosignals. 2009;17(2):162-8. doi: 10.1159/000205525. Epub 2009 Mar 4.
Nitric oxide (NO) and p38 have been shown to be involved in the ischemia/hypoxia-induced neuronal injury. In this study, we examined the activation patterns of mitogen-activated protein kinases and explored the relationship between NO and p38 in a model of hippocampal neuronal death induced by hypoxia/reoxygenation (H/R). p38 activity increased robustly during hypoxia and after reoxygenation, while the increase of c-Jun amino-terminal kinase and extracellular signal-related kinase activities showed mild tendency. Inhibition of p38 with SB203580 or SB202190 rescued neuronal death, whereas inhibition of extracellular signal-related kinases with PD98059 or c-Jun amino-terminal kinases with SP600125 offered no protection. p38 inhibitors also reduced neuronal death induced by the NO donor S-nitrosoglutathione. L-NAME, a nonspecific NO synthase inhibitor, blocked the p38 activation and rescued H/R-induced neuronal death. These results suggest that NO is an upstream signal of p38 that mediates the H/R-induced neuronal death.
一氧化氮（NO）和p38已被证明参与缺血/缺氧诱导的神经元损伤。在本研究中，我们检测了丝裂原活化蛋白激酶的激活模式，并在缺氧/复氧（H/R）诱导的海马神经元死亡模型中探究了NO与p38之间的关系。在缺氧期间和复氧后，p38活性显著增加，而c-Jun氨基末端激酶和细胞外信号相关激酶活性的增加呈轻度趋势。用SB203580或SB202190抑制p38可挽救神经元死亡，而用PD98059抑制细胞外信号相关激酶或用SP600125抑制c-Jun氨基末端激酶则无保护作用。p38抑制剂还可减少由NO供体S-亚硝基谷胱甘肽诱导的神经元死亡。非特异性NO合酶抑制剂L-NAME可阻断p38的激活并挽救H/R诱导的神经元死亡。这些结果表明，NO是p38的上游信号，介导H/R诱导的神经元死亡。
