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Oxidative Stress Partially Contributes to Iron-Induced Alpha-Synuclein Aggregation in SK-N-SH Cells

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Abstract

Intracellular Lewy body formation is one of the hallmarks of Parkinson’s disease (PD). As its main component, aggregated alpha-synuclein is presented in the substantia nigra, the same region iron accumulation occurs. In this study, the relationship between iron and alpha-synuclein aggregation was investigated. In the remaining cells, 1 mmol/l ferric and ferrous iron could induce cell loss in SK-N-SH cells and alpha-synulein aggregation. Pretreatment with 5 μmol/l vitamin E, a potent intracellular reactive oxygen species (ROS) scavenger could totally abolish ROS formation and cell viability reduction induced by ferric and ferrous iron treatment. However, the intracellular alpha-synuclein aggregation could only be partially alleviated. Due to the predicted iron responsive element (IRE) in the 5′-untranslated region of the human alpha-synuclein mRNA contains, we observed that alpha-synuclein mRNA level was up-regulated in SK-N-SH cells with iron regulatory protein (IRP) knockdown and more alpha-synuclein aggregations were observed in cells. The results suggest that iron-induced intracellular aggregated alpha-synuclein is partially dependent on oxidative stress and iron might also regulate alpha-synuclein aggregation through the IRE/IRP system.

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Acknowledgments

This work was supported by grants from the National Program of Basic Research sponsored by the Ministry of Science and Technology of China (2006CB500704), the National Foundation of Natural Science of China (30930036, 30870858), and the Natural Science Fund of Shandong Province for Distinguished Young Scholars (JQ200807).

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  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

    Wenjing Li, Hong Jiang, Ning Song & Junxia Xie

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  1. Wenjing Li
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  2. Hong Jiang
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  3. Ning Song
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  4. Junxia Xie
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Correspondence to Junxia Xie.

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Li, W., Jiang, H., Song, N. et al. Oxidative Stress Partially Contributes to Iron-Induced Alpha-Synuclein Aggregation in SK-N-SH Cells. Neurotox Res 19, 435–442 (2011). https://doi.org/10.1007/s12640-010-9187-x

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