Involvement of the NMDA receptor nitric oxide signal pathway in platelet-activating factor-induced neurotoxicity

被引:47
作者
Xu, Y
Tao, YX [1 ]
机构
[1] Nanjing Univ, State Key Lab Pharmaceut Biotechnol, Nanjing 210000, Peoples R China
[2] Nanjing Univ, Inst Mol & Cell Biol, Nanjing 210000, Peoples R China
[3] Nanjing Univ, Sch Med, Affiliated Drum Tower Hosp, Dept Neurol, Nanjing 210000, Peoples R China
[4] Johns Hopkins Univ, Sch Med, Dept Anesthesiol & Crit Care Med, Baltimore, MD 21205 USA
关键词
cell culture; neuronal death; nitric oxide; NMDA receptor; PAF;
D O I
10.1097/00001756-200402090-00010
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Platelet-activating factor (PAF), a bioactive phospholipid implicated in neuronal excitotoxic death, augments the presynaptic release of glutamate. Excessive activation of postsynaptic glutamate receptors and subsequent downstream signals leads to excitotoxicity. The present study proposed that the NMDA receptor/nitric oxide (NO) signal pathway might be involved in PAF-induced neurotoxicity. After the cultured neurons were exposed to RAF for 24 h the percentage of neuronal death increased in a dose-dependent manner. The PAF effects were significantly prevented not only by BN52021, a PAF antagonist, but also by MK-801, an NMDA antagonist, and L-NAME, an NO synthase (NOS) inhibitor. Moreover, the increases in NOS activity and neuronal NOS expression induced by chronic exposure of the cultured neurons to PAF were dramatically blocked by BN52021 and MK-801, respectively. Our findings suggest that the NMDA receptor/NO signaling pathway might contribute to the pathological mechanism of cell death triggered via PAF receptor activation.
引用
收藏
页码:263 / 266
页数:4
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