Abstract
Exposure of cells to paraquat leads to production of superoxide anion (O 2 − ). This reacts with hydrogen peroxide to give the hydroxyl radical ( OH), leading to lipid peroxidation and cell death. In this study, we investigated the effects of cellular prion protein (PrP C) overexpression on paraquat-induced toxicity by using an established model system, rabbit kidney epithelial A74 cells, which express a doxycycline-inducible murine PrP C gene. PrP C overexpression was found to significantly reduce paraquat-induced cell toxicity, DNA damage, and malondialdehyde acid levels. Superoxide dismutase (total SOD and CuZn-SOD) and glutathione peroxidase activities were higher in doxycycline-stimulated cells. Our findings clearly show that PrP C overexpression plays a protective role against paraquat toxicity, probably by virtue of its superoxide dismutase-like activity.
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