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. 2008 Jul 19;24(3):125–132. doi: 10.1007/s12264-008-1214-z

Iron contributes to the formation of catechol isoquinolines and oxidative toxicity induced by overdose dopamine in dopaminergic SH-SY5Y cells

铁离子促进过量多巴胺引起 SH-SY5Y 细胞儿茶酚异喹啉物质生成和氧化损伤

Ran Wang 1, Hong Qing 1, Xiao-Qian Liu 1, Xiao-Lin Zheng 1, Yu-Lin Deng 1,✉
PMCID: PMC5552540  PMID: 18500384

Abstract

Objective

The selective loss of dopaminergic neurons in Parkinson’s disease is suspected to correlate with the increase of cellular iron, which may be involved in the pathogenesis of PD by promotion of oxidative stress. This research investigated dopamine-induced oxidative stress toxicity contributed by iron and the production of dopamine-derived neurotoxins in dopaminergic SH-SY5Y cells.

Methods

After the SH-SY5Y cells were pre-incubated with dopamine and Fe2+ for 24 h, the cell viability, hydroxyl radical, melondialdehyde, cell apoptosis, and catechol isoquinolines were measured by lactate dehydrogenase assay, salicylic acid trapping method, thiobarbuteric acid assay, Hoechst 33258 staining and HPLC-electrochemical detection (HPLC-ECD), respectively.

Results

(1) Optimal dopamine (150 μmol/L) and Fe2+ (40 or 80 μmol/L) significantly increased the concentrations of hydroxy radicals and melondialdehyde in SH-SY5Y cells. (2) Induction with dopamine alone or dopamine and Fe2+ (dopamine/Fe2+) caused cell apoptosis. (3) Compared with untreated cells, the catechol isoquinolines, salsolinol and N-methyl-salsolinol in dopamine/Fe2+-induced cells were detected in increasing amounts.

Conclusion

Due to dopamine/Fe2+-induced oxidative stress similar to the state in the parkinsonian substantia nigra neurons, dopamine and Fe2+ impaired SH-SY5Y cells could be used as the cell oxidative stress model of Parkinson’s disease. The catechol isoquinolines detected in cells may be involved in the pathogenesis of Parkinson’s disease as potential neurotoxins.

Keywords: Parkinson’s disease, Fe2+, dopamine, oxidative stress, salsolinol, N-methyl-salsolinol

Footnotes

The authors contributed equally to this work

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