Contrasting antioxidant and cytotoxic effects of peroxiredoxin I and II in PC12 and NIH3T3 cells.
We examined the impact of peroxiredoxin-I (Prx-I) and peroxiredoxin-II (Prx-II) stable transduction on oxidative stress in PC12 neurons and NIH3T3 fibroblasts and found variability depending on cell type and Prx subtype. In PC12 neurons, Prx-II suppressed reactive oxygen species (ROS) generation by 36% (p < 0.01) relative to vector-infected control cells. However, in NIH3T3 fibroblasts, Prx-II overexpression resulted in a 97% (p < 0.01) increase in ROS generation. Prx-I transduction elevated ROS generation in PC12 cells. The effect of Prx-I on PC12 cells was potentiated in the presence of menadione, and suppressed by an inhibitor of nitric oxide synthetase. Prx-II transduction resulted in 25-35% lower levels of glutathione (GSH) in both cell types, while Prx-I transduction increased GSH levels in neurons and decreased GSH and caspase-3 activity in fibroblasts. Prx-I and Prx-II also had differing effects on cell viability. These results suggest that Prx-I and Prx-II can either increase or decrease intracellular oxidative stress depending on cell type or experimental conditions, particularly conditions affecting nitric oxide levels.
Simzar
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S
Department of Medicine, Center for Health Sciences, UCLA School of Medicine, Los Angeles, CA 90095, USA.
Ellyin
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R
Shau
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Sarafian
T A
TA
D016475:3T3 Cells; D000818:Animals; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D005978:Glutathione / Q000037:antagonists & inhibitors; D051379:Mice; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D016716:PC12 Cells; D010544:Peroxidases / Q000235:genetics / Q000378:metabolism*; D054464:Peroxiredoxins; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D014162:Transfection
D017382:Reactive Oxygen Species; D010544:Peroxidases; D054464:Peroxiredoxins; C505409:Casp3 protein, mouse; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases; D005978:Glutathione