Oxidative stress partially contributes to iron-induced α-synuclein aggregation in SK-N-SH cells.
Intracellular Lewy body formation is one of the hallmarks of Parkinson's disease (PD). As its main component, aggregated α-synuclein is presented in the substantia nigra, the same region iron accumulation occurs. In this study, the relationship between iron and α-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 α-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 α-synuclein aggregation could only be partially alleviated. Due to the predicted iron responsive element (IRE) in the 5'-untranslated region of the human α-synuclein mRNA contains, we observed that α-synuclein mRNA level was up-regulated in SK-N-SH cells with iron regulatory protein (IRP) knockdown and more α-synuclein aggregations were observed in cells. The results suggest that iron-induced intracellular aggregated α-synuclein is partially dependent on oxidative stress and iron might also regulate α-synuclein aggregation through the IRE/IRP system.
Li
Wenjing
W
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, China.
Jiang
Hong
H
Song
Ning
N
Xie
Junxia
J
D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D005290:Ferric Compounds / Q000633:toxicity*; D005296:Ferrous Compounds / Q000633:toxicity*; D006801:Humans; D018384:Oxidative Stress / Q000187:drug effects / Q000235:genetics*; D011237:Predictive Value of Tests; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics; D051844:alpha-Synuclein / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*
D005290:Ferric Compounds; D005296:Ferrous Compounds; D012333:RNA, Messenger; C497604:SNCA protein, human; D051844:alpha-Synuclein
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