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

被引：57
作者：
Li, Wenjing [1 ,2 ]
Jiang, Hong [1 ,2 ]
Song, Ning [1 ,2 ]
Xie, Junxia [1 ,2 ]
机构：
[1] Qingdao Univ, Dept Physiol, Shandong Prov Key Lab Pathogenesis & Prevent Neur, Qingdao 266071, Peoples R China
[2] Qingdao Univ, Coll Med, State Key Disciplines Physiol, Qingdao 266071, Peoples R China
来源：
NEUROTOXICITY RESEARCH | 2011年 / 19卷 / 03期
关键词：
Parkinson's disease; Alpha-synuclein; Iron; Vitamin E; Oxidative stress; Iron responsive element; Iron regulatory protein; PARKINSONS-DISEASE; SUBSTANTIA-NIGRA; LEWY BODIES; NEURODEGENERATIVE DISEASES; DOPAMINERGIC-NEURONS; RESPONSIVE ELEMENT; MUTATION; DEMENTIA; NEUROPATHOLOGY; ACCUMULATION;
D O I：
10.1007/s12640-010-9187-x
中图分类号：
Q189 [神经科学];
学科分类号：
071006 ;
摘要：
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 mu mol/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.
引用
收藏
页码：435 / 442
页数：8
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