Human neuroblastoma cells transfected with tyrosine hydroxylase gain increased resistance to methylmercury-induced cell death.
In a previous study we demonstrated 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 pro-oxidants than wild type SH-SY5Y cells (SH cells). In the present communication we used methylmercury as a model of cell stress in order to test whether SH+TH cells would behave in a similar manner in response to this stressor. Incubation with methylmercury (0.1-3 microM) for 24h caused a significant reduction in cell viability and increased apoptotic markers in both cell types. However, the effects were significantly reduced in the SH+TH cells when compared to the SH cells. Activation of p38(MAPK) was also reduced in the SH+TH compared to the SH cells after methylmercury exposure. Since p38(MAPK) is known to participate in signal transduction pathways during cell stress, our data suggest that SH+TH cells develop an increased resistance to environmental stress caused by neurotoxins such as methylmercury. In conclusion our results show that insertion of the human TH gene in cells that originally do not express this protein leads to alterations in cell homeostasis and triggers defense mechanisms against pro-oxidative insults.
Posser
Thaís
T
Departamento de Química, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria, Brazil.
Dunkley
Peter R
PR
Dickson
Phillip W
PW
Franco
Jeferson Luis
JL
D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004351:Drug Resistance / Q000187:drug effects; D006801:Humans; D020935:MAP Kinase Signaling System / Q000502:physiology; D008767:Methylmercury Compounds / Q000633:toxicity*; D009447:Neuroblastoma / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D009498:Neurotoxins / Q000633:toxicity*; D010766:Phosphorylation; D014162:Transfection; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D008767:Methylmercury Compounds; D009498:Neurotoxins; D014446:Tyrosine 3-Monooxygenase; D048051:p38 Mitogen-Activated Protein Kinases