S-腺苷甲硫氨酸增加salsolinol对多巴胺能神经细胞SH-SY5Y的毒性

doi:10.3969/j.issn.1006-7795.2015.06.014

摘要/Abstract

摘要： 目的帕金森病(Parkinson's disease,PD)是常见的神经退行性疾病,儿茶酚异喹啉类神经毒素(salsolinol,Sal)作为内源性神经毒素是其可能的致病因素,而S-腺苷甲硫氨酸(S-adenosyl methionine,SAM)目前在帕金森病的治疗上有应用的可能,所以有必要对其在体内的作用进行研究。方法本实验采用体外培养的多巴胺能细胞SH-SY5Y,首先使用MTT的方法对Sal以及SAM与Sal共同诱导后细胞存活率进行研究,使用了Hoechst 33258染色的方式检测凋亡,并检测ATP,最后使用高效液相色谱偶联电化学检测器(high performance liquid chromatography couple electrochemical detector,HPLC-ECD)检测了Sal和SAM代谢生成的氮甲基去甲猪毛菜碱(N-methylsalsolinol,NMSal)在细胞中的浓度。结果 SAM可以促进Sal引起的细胞存活率的降低,同时凋亡水平升高,ATP浓度降低,而且SAM诱导之后,Sal代谢生成的NMSal浓度也随之升高。结论这些结果说明了SAM会促进Sal在多巴胺能神经细胞中的毒性作用,因此SAM可能不利于PD的治疗。

关键词: 帕金森病, 儿茶酚异喹啉, S-腺苷甲硫氨酸, 儿茶酚异喹啉类神经毒素

Abstract: Objective Parkinson's disease(PD) is a common neurodegenerative disease, and salsolinol which is catechol tetrahydroisoquinoline may play important role in the pathogenesis of PD. S-adenosyl methionine(SAM) may be used in the medical treatment of PD, and it is very meaningful to study the mechanism of it. Methods In our study, we chose SH-SY5Y as cell model, and used MTT to test the survival rate induced by Sal or Sal combined SAM. The apoptosis of them was detected by Hoechst 33258 stain, and the ATP level was also measured. The NMSal level which is the product of Sal N-methylation was detected by the HPLC-ECD. Results SAM can decrease the survival rate under Sal, and increased the apoptosis. The ATP level was lower in the SAM combined groups. SAM can make the cell produce more NMSal in the Sal induced groups. Conclusion These results indicated that SAM can enhance the toxicity of Sal in the dopaminergic neurons, and it may adverse to the cure of PD.

Key words: Parkinson's disease, catechol tetrahydroisoquinoline, S-adenosyl methionine, salsolinol

中图分类号:

R592

卢剑清, 邓玉林. S-腺苷甲硫氨酸增加salsolinol对多巴胺能神经细胞SH-SY5Y的毒性[J]. 首都医科大学学报, 2015, 36(6): 915-920.

Lu Jianqing, Deng Yulin. S-adenosyl methionine enhance the toxicity of salsolinol in dopaminergic SH-SY5Y cell[J]. Journal of Capital Medical University, 2015, 36(6): 915-920.

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