Xu Yun, Tao Yuan-Xiang
Department of Neurology, The Affiliated Drum Tower Hospital of Nanjing University School of Medicine, Nanjing University, Nanjing 210000, PR China.
Neuroreport. 2004 Feb 9;15(2):263-6. doi: 10.1097/00001756-200402090-00010.
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 PAF 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.
血小板活化因子（PAF）是一种与神经元兴奋性毒性死亡有关的生物活性磷脂，可增强谷氨酸的突触前释放。突触后谷氨酸受体的过度激活及随后的下游信号会导致兴奋性毒性。本研究提出，N-甲基-D-天冬氨酸（NMDA）受体/一氧化氮（NO）信号通路可能参与PAF诱导的神经毒性。将培养的神经元暴露于PAF 24小时后，神经元死亡百分比呈剂量依赖性增加。PAF的作用不仅被PAF拮抗剂BN52021显著抑制，还被NMDA拮抗剂MK-801和NO合酶（NOS）抑制剂L-NAME显著抑制。此外，BN52021和MK-801分别显著阻断了培养的神经元长期暴露于PAF所诱导的NOS活性增加和神经元型NOS表达增加。我们的研究结果表明，NMDA受体/NO信号通路可能参与了通过PAF受体激活触发的细胞死亡的病理机制。
