School of Life Science, Beijing Institute of Technology, 5 South Zhongguancun Street, Haidian District, Beijing 100081, PR China.
Neurosci Lett. 2013 Jun 28;547:65-9. doi: 10.1016/j.neulet.2013.05.012. Epub 2013 May 14.
Alpha-synuclein is one of the important components of Lewy body which involved in neuropathology of Parkinson's disease (PD). The relationship between α-synuclein and cell death is still unclear. In the study, PC12 cell, stably over expressing α-synuclein model was used, and we investigated the level of intracellular oxidative stress, dopamine and endogenous neurotoxin. The results showed that the level of oxidative stress and intracytoplasmic dopamine (DA) was increased in cells over expressing α-synuclein compared with normal PC12 cells. Simultaneously, additional generation of endogenous neurotoxins 1-methyl-4-phenyl-1,2,3,4-tetrahydroisoquinoline (salsolinol) and 1(R),2(N)-dimethyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinolin (NM-salsolinol) was detected and this phenomenon was exacerbated after exposed to H₂O₂ for 24 h, but mitigated when treated with dopamine synthesis inhibitors. The presence of endogenous neurotoxins exacerbated α-synuclein induced mitochondrial damage. These results suggest that the endogenous neurotoxins may become a bridge between α-synuclein and cell death.
α-突触核蛋白是路易体的重要组成部分之一，与帕金森病（PD）的神经病理学有关。α-突触核蛋白与细胞死亡之间的关系尚不清楚。在这项研究中，我们使用了稳定过表达α-突触核蛋白的 PC12 细胞模型，研究了细胞内氧化应激、多巴胺和内源性神经毒素的水平。结果表明，与正常 PC12 细胞相比，过表达α-突触核蛋白的细胞中氧化应激和细胞内多巴胺（DA）水平升高。同时，检测到内源性神经毒素 1-甲基-4-苯基-1,2,3,4-四氢异喹啉（salsolinol）和 1（R），2（N）-二甲基-6,7-二羟基-1,2,3,4-四氢异喹啉（NM-salsolinol）的额外生成，并且这种现象在暴露于 H₂O₂ 24 小时后加剧，但在用多巴胺合成抑制剂处理时减轻。内源性神经毒素的存在加剧了α-突触核蛋白诱导的线粒体损伤。这些结果表明，内源性神经毒素可能成为α-突触核蛋白与细胞死亡之间的桥梁。
