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

Autor: Franco, Jeferson L., Posser, Thaís, Gordon, Sarah L., Bobrovskaya, Larisa, Schneider, Jennifer J., Farina, Marcelo, Dafre, Alcir L., Dickson, Phillip W., Dunkley, Peter R.
Předmět:
Zdroj: Toxicological Sciences; Jan2010, Vol. 113 Issue 1, p150-157, 8p, 1 Chart, 7 Graphs
Abstrakt: 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. [ABSTRACT FROM PUBLISHER]
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