Ceramide selectively inhibits apoptosis-associated events in NGF-deprived sympathetic neurons.
Ceramide selectively inhibits apoptosis-associated events in NGF-deprived sympathetic neurons.
复制标题
神经酰胺选择性抑制 NGF 缺失的交感神经元中与细胞凋亡相关的事件。
DOI：
10.1038/sj.cdd.4400628
复制
发表时间：
2000
影响因子：
12.4
通讯作者：
Estus,S
中科院分区：
文献类型：
--
作者：
Nair,P;Tammariello,SP;Estus,S
根据实验系统，神经酰胺表现出神经毒性和神经保护特性。 Ito 和 Horigome 先前报道，神经酰胺在发育程序性细胞死亡的经典模型（即交感神经元经历 NGF 剥夺）中延迟细胞凋亡。 1 在此，我们研究了神经酰胺对 NGF 缺失神经元中发生的生化和遗传变化的作用。我们将神经酰胺的神经保护作用与神经酰胺拮抗 NGF 剥夺诱导的氧化应激和 c-jun 诱导的能力联系起来，这两者都有助于该模型中的细胞凋亡。然而，神经酰胺并不能阻止 NGF 剥夺引起的 RNA 和蛋白质合成下降，这表明神经酰胺并不能减缓所有与细胞凋亡相关的事件。总体而言，这些结果意义重大，因为它们表明神经酰胺在死亡级联的早期发挥作用，拮抗 NGF 剥夺诱导神经元凋亡所必需的两个事件。此外，这些结果将神经元功能（即大分子合成）的下降与神经元死亡级联分离。
Ceramide manifests both neurotoxic and neuroprotective properties depending on the experimental system. Ito and Horigome previously reported that ceramide delays apoptosis in a classic model of developmental programmed cell death, ie sympathetic neurons undergoing NGF deprivation. 1 Here, we investigated the actions of ceramide upon the biochemical and genetic changes that occur in NGF deprived neurons. We correlate ceramide's neuroprotective actions with the ability of ceramide to antagonize NGF deprivation-induced oxidative stress and c-jun induction, both of which contribute to apoptosis in this model. However, ceramide did not block NGF deprivation-induced declines in RNA and protein synthesis, suggesting that ceramide does not slow all apoptosis-related events. Overall, these results are significant in that they show that ceramide acts early in the death cascade to antagonize two events necessary for NGF-deprivation induced neuronal apoptosis. Moreover, these results dissociate declines in neuronal function, ie macromolecular synthesis, from the neuronal death cascade.