Dose-and time-dependentα-synuclein aggregation induced by ferric iron in SK-N-SH cells  

铁离子对α-突触核蛋白聚集的诱发作用具有剂量和时间依赖性(英文)

作　　者：李文静[1] 姜宏[1] 宋宁[1] 谢俊霞[1] 

机构地区：[1]山东省神经相关疾病机制与防治重点实验室,青岛大学国家生理学重点(培育)学科,青岛266071

出　　处：《Neuroscience Bulletin》2010年第3期205-210,共6页神经科学通报（英文版）

基　　金：supported by the grants from the National Basic Research Development Program of China(No.2006CB500704);the National Natural Science Foundation of China(No.30930036,30870858);the Natural Science Fund for Distinguished Young Scholars of Shandong Province,China(No.JQ200807)

摘　　要：Objective Intracellular formation of Lewy body （LB） is one of the hallmarks of Parkinson’s disease.The main component of LB is aggregatedα-synuclein,present in the substantia nigra where iron accumulation also occurs.The present study was aimed to study the relationship between iron andα-synuclein aggregation.Methods SK-N-SH cells were treated with different concentrations of ferric iron for 24 h or 48 h.MTT assay was conducted to determine the cell viability. Thioflavine S staining was used to detectα-synuclein aggregation.Results With the increase of iron concentration,the cell viability decreased significantly.At the concentrations of 5 mmol/L and 10 mmol/L,iron inducedα-synuclein aggregation more severely than at the concentration of 1 mmol/L.Besides,48-h treatment-induced aggregation was more severe than that induced by 24-h treatment,at the corresponding iron concentrations.Conclusion Ferric iron can induceα-synuclein aggregation,which is toxic to the cells,in a dose-and time-dependent way.目的帕金森氏病的一个重要标志是胞浆内路易小体的形成。路易小体的主要成分是α-突触核蛋白的聚集体,它和铁的积聚一同存在于黒质区。本实验旨在研究铁和α-突触核蛋白聚集的关系。方法 SK-N-SH细胞在不同浓度的三价铁作用下,分别孵育24h或48h,用MTT法和硫磺素S染色法分别检测细胞存活率、观察α-突触核蛋白的聚集情况。结果随着铁离子浓度的升高,细胞存活率显著下降。其中5mmol/L和10mmol/L三价铁引起的α-突触核蛋白的聚集相较于1mmol/L的三价铁引起的聚集更为严重。此外,在同一浓度的三价铁作用下,孵育48h引起的聚集比孵育24h引起的聚集更严重。结论铁离子诱发的α-突触核蛋白的聚集具有剂量和时间的依赖性,并且α-突触核蛋白的聚集介导了铁的毒性作用。

关 键 词：Parkinson’s disease Α-SYNUCLEIN ferric ammonium citrate 

分 类 号：R742.5[医药卫生—神经病学与精神病学]