Prasad K N, La Rosa F G, Prasad J E
Center for Vitamins and Cancer Research, Department of Radiology, School of Medicine, University of Colorado Health Sciences Center, Denver 80262-0278, USA.
In Vitro Cell Dev Biol Anim. 1998 Mar;34(3):265-74. doi: 10.1007/s11626-998-0133-7.
Although chronic inflammatory reactions have been proposed to cause neuronal degeneration associated with Alzheimer's disease (AD), the role of prostaglandins (PGs), one of the secretory products of inflammatory reactions, in degeneration of nerve cells has not been studied. Our initial observation that PGE1-induced differentiated neuroblastoma (NB) cells degenerate in vitro more rapidly than those induced by RO20-1724, an inhibitor of cyclic nucleotide phosphodiesterase, has led us to postulate that PGs act as a neurotoxin. This study has further investigated the effects of PGs on differentiated NB cells in culture. Results showed that PGA1 was more effective than PGE1 in causing degeneration of differentiated NB cells as shown by the cytoplasmic vacuolation and fragmentation of soma, nuclei, and neurites. Because increased levels of ubiquitin and beta-amyloid have been implicated in causing neuronal degeneration, we studied the effects of PGs on the levels of these proteins during degeneration of NB cells in vitro by an immunostaining technique, using primary antibodies to ubiquitin and beta-amyloid. Results showed that PGs increased the intracellular levels of ubiquitin and beta-amyloid prior to degeneration, whereas the degenerated NB cells had negligible levels of these proteins. These data suggest that PGs act as external neurotoxic signals which increase levels of ubiquitin and beta-amyloid that represent one of the intracellular signals for initiating degeneration of nerve cells.
尽管有人提出慢性炎症反应会导致与阿尔茨海默病（AD）相关的神经元变性，但炎症反应的分泌产物之一前列腺素（PGs）在神经细胞变性中的作用尚未得到研究。我们最初观察到，在体外，前列腺素E1（PGE1）诱导分化的神经母细胞瘤（NB）细胞变性的速度比环核苷酸磷酸二酯酶抑制剂RO20 - 1724诱导的细胞更快，这使我们推测PGs可作为一种神经毒素。本研究进一步探讨了PGs对培养的分化NB细胞的影响。结果表明，前列腺素A1（PGA1）在导致分化的NB细胞变性方面比PGE1更有效，表现为细胞质空泡化以及细胞体、细胞核和神经突的碎片化。由于泛素和β - 淀粉样蛋白水平升高与神经元变性有关，我们通过免疫染色技术，使用针对泛素和β - 淀粉样蛋白的一抗，研究了PGs在体外NB细胞变性过程中对这些蛋白质水平的影响。结果显示，在变性之前，PGs会增加细胞内泛素和β - 淀粉样蛋白的水平，而变性的NB细胞中这些蛋白质的水平可忽略不计。这些数据表明，PGs作为外部神经毒性信号，会增加泛素和β - 淀粉样蛋白的水平，而这代表了启动神经细胞变性的细胞内信号之一。
