Journal Article

Expression of Tyrosine Hydroxylase Increases the Resistance of Human Neuroblastoma Cells to Oxidative Insults

Jeferson L. Franco, Thaís Posser, Sarah L. Gordon, Larisa Bobrovskaya, Jennifer J. Schneider, Marcelo Farina, Alcir L. Dafre, Phillip W. Dickson and Peter R. Dunkley

in Toxicological Sciences

Volume 113, issue 1, pages 150-157
Published in print January 2010 | ISSN: 1096-6080
Published online October 2009 | e-ISSN: 1096-0929 | DOI: http://dx.doi.org/10.1093/toxsci/kfp245
Expression of Tyrosine Hydroxylase Increases the Resistance of Human Neuroblastoma Cells to Oxidative Insults

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In this study, we demonstrate that human neuroblastoma SH-SY5Y cells transfected with human tyrosine hydroxylase isoform 1 (SH + TH cells) were substantially more resistant to cell death induced by hydrogen peroxide and 6-hydroxydopamine when compared to wild-type SH-SY5Y cells (SH cells). SH + TH cells exhibit increased levels of dopamine (DA) compared to SH cells. Incubation with hydrogen peroxide or 6-hydroxydopamine (10–100μM) for 24 h caused a significant reduction in cell viability and increased apoptosis in both cell types. However, these effects were significantly reduced in the SH + TH cells when compared to the SH cells. The SH + TH cells showed an improved ability to detoxify peroxide, which correlated with an increase in glutathione peroxidase and glutathione reductase activities, while catalase activity was unchanged. Our data suggest that a preconditioning-like mechanism linked to higher DA levels increased the resistance of SH + TH cells against oxidative insults, which is at least in part related to an augmentation in the activity of glutathione-related antioxidant enzymes.

Keywords: tyrosine hydroxylase; dopamine; oxidative stress; glutathione peroxidase; glutathione reductase

Journal Article.  5874 words.  Illustrated.

Subjects: Medical Toxicology ; Toxicology (Non-medical)

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