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Dose- and time-dependent α-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

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Abstract

Objective

Intracellular formation of Lewy body (LB) is one of the hallmarks of Parkinson’s disease. The main component of LB is aggregated α-synuclein, present in the substantia nigra where iron accumulation also occurs. The present study was aimed to study the relationship between iron and α-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 detect α-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 induced α-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 induce α-synuclein aggregation, which is toxic to the cells, in a dose- and time-dependent way.

摘要

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24 h 或48 h, 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5 mmol/L 和10 mmol/L 三价铁引起的α- 突触核蛋白的聚集相较于1 mmol/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48 h引起的聚集比孵育24 h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。

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Authors and Affiliations

  1. Department of Physiology, Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders and State Key Disciplines: Physiology, Medical College of Qingdao University, Qingdao, 266071, China

    Wen-Jing Li  (李文静), Hong Jiang  (姜宏), Ning Song  (宋宁) & Jun-Xia Xie  (谢俊霞)

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  1. Wen-Jing Li  (李文静)
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  2. Hong Jiang  (姜宏)
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Correspondence to Jun-Xia Xie  (谢俊霞).

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Li, WJ., Jiang, H., Song, N. et al. Dose- and time-dependent α-synuclein aggregation induced by ferric iron in SK-N-SH cells. Neurosci. Bull. 26, 205–210 (2010). https://doi.org/10.1007/s12264-010-1117-7

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  • DOI: https://doi.org/10.1007/s12264-010-1117-7

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