ToxSci Advance Access published online on October 8, 2009
Toxicological Sciences, doi:10.1093/toxsci/kfp245
Expression of Tyrosine Hydroxylase Increases the Resistance of Human Neuroblastoma Cells to Oxidative Insults
1 Centro de Ciências Rurais, Universidade Federal do Pampa, São Gabriel – RS, 97300-000, Brazil 2 The School of Biomedical Science and Hunter Medical Research Institute, Faculty of Health, The University of Newcastle, Callaghan, Australia 3 Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis – SC, 88040-900, Brazil 4 Departamento de Ciências Fisiológicas, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis – SC, 88040-900, Brazil
Corresponding author: Jeferson Luis Franco, Universidade Federal do Pampa, São Gabriel, RS, 97300-000, Brazil. E-mail: jefersonbio{at}hotmail.com
Received August 25, 2009; revision received October 1, 2009; accepted October 1, 2009
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Abstract |
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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 compared to SH cells. Incubation with hydrogen peroxide or 6-hydroxydopamine (10 – 100 µM) for 24 hours 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 activity, while catalase activity was unchanged. Our data suggests that a preconditioning-like mechanism linked to higher dopamine 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.
Key Words: glutathione; Biotransformation and Toxicokinetics, apoptosis; Carcinogenesis, cell lines, transfected; In Vitro and Altenatives, cytotoxicity; In Vitro and Altenatives, oxidative injury; Systems Toxicology.