Jeohn G H, Kim W G, Hong J S
Neuropharmacology Section, Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, National Institutes of Health, P.O. Box 12233, Research Triangle Park, NC 27709, USA.
Brain Res. 2000 Oct 13;880(1-2):173-7. doi: 10.1016/s0006-8993(00)02737-2.
We investigated the time-dependency of the action of nitric oxide (NO) on glia-mediated neuronal cell death. Cortical neuron-glia co-cultures were treated with lipopolysaccharide and interferon gamma (LPS/IFNgamma). The production of NO was first detectable 9 h after the exposure to LPS/IFNgamma and increased for up to 48 h. A significant neuronal cell death was observed 36-48 h after treatment with LPS/IFNgamma. The NO generated at the initial stage of NO synthesis (about 12 h) following exposure to LPS/IFNgamma was found to be critical for LPS/IFNgamma-induced neurotoxicity. Furthermore, the rate of NO production at the initial stage of NO synthesis was correlated linearly with the extent of neuronal cell death. These findings suggest that the maximal rate of NO synthesis, instead of the accumulated NO(2)(-) level, is a sensitive index for predicting endotoxin-induced cytotoxicity.
我们研究了一氧化氮（NO）对神经胶质细胞介导的神经元细胞死亡作用的时间依赖性。用脂多糖和干扰素γ（LPS/IFNγ）处理皮质神经元-神经胶质细胞共培养物。暴露于LPS/IFNγ后9小时首次检测到NO的产生，并持续增加至48小时。在用LPS/IFNγ处理后36-48小时观察到显著的神经元细胞死亡。发现暴露于LPS/IFNγ后在NO合成初始阶段（约12小时）产生的NO对LPS/IFNγ诱导的神经毒性至关重要。此外，NO合成初始阶段的NO产生速率与神经元细胞死亡程度呈线性相关。这些发现表明，NO合成的最大速率而非累积的NO₂⁻水平是预测内毒素诱导的细胞毒性的敏感指标。
