Café C, Torri C, Bertorelli L, Angeretti N, Lucca E, Forloni G, Marzatico F
Institute of Pharmacology, University of Pavia, Italy.
Neurosci Lett. 1996 Jan 12;203(1):61-5. doi: 10.1016/0304-3940(95)12250-8.
The aim of this work was to investigate whether free radical reactions play a role in beta-amyloid neurotoxicity. Rat cortical neurons were exposed acutely (24 h) or chronically (3, 7 days) to beta-amyloid biologically active fragment beta 25-35 (50 microM). In these conditions, where only the longest exposure induced neuronal death, superoxide dismutase activity was increased after acute exposure but no change was detected after chronic treatments, whereas a different pattern was observed for glutathione peroxidase. In the basal condition, there was an eight-fold increase in dichlorofluoroscein, used as peroxide production marker, in neuronal cells after 7 days treatment with beta 25-35. Moreover, the intracellular peroxide production induced by Fe2+/ascorbate stimulation was amplified by beta 25-35, increasingly up to 7 days of exposure, by which time the dichlorofluoroscein-stimulated levels were 33 times higher than in controls. In conclusion, our results show that oxidative stress and free radical production are linked to beta 25-35 exposure and may contribute to neurodegenerative events associated with beta-amyloid deposits in Alzheimer's disease.
这项工作的目的是研究自由基反应是否在β-淀粉样蛋白神经毒性中起作用。将大鼠皮质神经元急性（24小时）或慢性（3天、7天）暴露于β-淀粉样蛋白生物活性片段β25-35（50微摩尔）。在这些条件下，只有最长时间的暴露诱导神经元死亡，急性暴露后超氧化物歧化酶活性增加，但慢性处理后未检测到变化，而谷胱甘肽过氧化物酶则呈现不同的模式。在基础条件下，用β25-35处理7天后，用作过氧化物产生标志物的二氯荧光素在神经元细胞中的含量增加了八倍。此外，β25-35增强了由Fe2+/抗坏血酸刺激诱导的细胞内过氧化物产生，直至暴露7天时，此时二氯荧光素刺激的水平比对照组高33倍。总之，我们的结果表明，氧化应激和自由基产生与β25-35暴露有关，可能导致与阿尔茨海默病中β-淀粉样蛋白沉积相关的神经退行性事件。
