Expression of tyrosine hydroxylase increases the resistance of human neuroblastoma cells to oxidative insults.
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 (10-100microM) 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.
Franco
Jeferson L
JL
Centro de Ciências Rurais, Universidade Federal do Pampa, São Gabriel, Rio Grande do Sul 97300-000, Brazil. jefersonbio@hotmail.com
Posser
Thaís
T
Gordon
Sarah L
SL
Bobrovskaya
Larisa
L
Schneider
Jennifer J
JJ
Farina
Marcelo
M
Dafre
Alcir L
AL
Dickson
Phillip W
PW
Dunkley
Peter R
PR
D017209:Apoptosis / Q000187:drug effects; D002330:Carmustine / Q000494:pharmacology; D002374:Catalase / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005979:Glutathione Peroxidase / Q000037:antagonists & inhibitors / Q000378:metabolism; D005980:Glutathione Reductase / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity; D009447:Neuroblastoma / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects; D016627:Oxidopamine / Q000633:toxicity; D013870:Thiomalates / Q000494:pharmacology; D014162:Transfection; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics / Q000378:metabolism*
D004791:Enzyme Inhibitors; D013870:Thiomalates; D016627:Oxidopamine; C046062:2-thiomalic acid; D006861:Hydrogen Peroxide; D002374:Catalase; D005979:Glutathione Peroxidase; D014446:Tyrosine 3-Monooxygenase; D005980:Glutathione Reductase; D002330:Carmustine; D004298:Dopamine