Extracellular dopamine induces the oxidative toxicity of SH-SY5Y cells

Synapse
Yuhua JiangFang Liu

Abstract

Dopamine-induced neuronal cytotoxicity has been proposed as a leading pathological mechanism underlying many neuronal degenerative disorders including Parkinson disease. Various hypotheses have been proposed including oxidative stress and dopamine (DA)-induced intracellular signal disorder via DA D1 and D2 receptors. The exact mechanism involved in this process is far from clear. In this study, employing a neuronal blastoma cell line, SH-SY5Y, we tried to elucidate the roles of these different suggested mechanisms in this pathological process. The results showed that DA induced cell toxicity in a dose- and time-dependent way. Selective D1 and D2 DA receptor antagonist could not block the cytotoxic effects, whereas reductive reagent ascorbic acid but not GSH could effectively rescue the cell death, suggesting that DA-induced cell toxicity was caused by an extracellular oxidative stress. This was further supported by the enhancing effects of DA transporter blocker, GBR, which could increase the cell death when pretreated. Finally, ascorbic acid could also protect SY5Y cells from DA-induced cellular apoptotic signal changes including PARP and P53. Our studies suggested that DA exerted its cytotoxic effects via an extracellular met...Continue Reading

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Citations

Jan 10, 2012·Cell Biology and Toxicology·Colette T DooleyJane H Thompson
Oct 2, 2012·DNA and Cell Biology·Monica ColamartinoRenata Cozzi
Dec 1, 2012·Toxicology Letters·Patrícia Silva FerreiraJoão Paulo Capela
Feb 29, 2016·Drug and Alcohol Dependence·Francesca Felicia CaputiPatrizia Romualdi
Oct 2, 2012·Brain Research Bulletin·James M MaySergey Dikalov
Dec 8, 2010·Neurochemistry International·Ling ZhangChunli Zhao
Sep 12, 2019·Scientific Reports·Juan Carlos CoronaMarcela Salazar-García
Sep 3, 2019·Nanomedicine : Nanotechnology, Biology, and Medicine·Mohammed Nadim SardoiwalaSubhasree Roy Choudhury

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