NR ARTE
AU Senator,A.; Rachidi,W.; Lehmann,S.; Favier,A.; Benboubetra,M.
TI Prion protein protects against DNA damage induced by paraquat in cultured cells
QU Free Radical Biology and Medicine 2004 Oct 15; 37(8): 1224-30
PT journal article
AB Exposure of cells to paraquat leads to production of superoxide anion (O2*-). 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 (PrPc) overexpression on paraquat-induced toxicity by using an established model system, rabbit kidney epithelial A74 cells, which express a doxycycline-inducible murine PrPc gene. PrPc 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 PrPc overexpression plays a protective role against paraquat toxicity, probably by virtue of its superoxide dismutase-like activity.
MH Animals; Cells, Cultured/chemistry/drug effects; *DNA Damage/drug effects; Doxycycline/pharmacology; Epithelial Cells/chemistry/drug effects; Gene Expression Regulation/drug effects; Glutathione Peroxidase/analysis; Kidney; Malondialdehyde/analysis; Mice; Oxidative Stress; Paraquat/*toxicity; PrPc Proteins/genetics/*physiology; Rabbits; Recombinant Fusion Proteins/physiology; Research Support, Non-U.S. Gov't; Superoxide Dismutase/analysis; Transfection
AD Laboratoire de Biologie du Stress Oxydant, Faculte de Pharmacie, Domaine de la Merci, La Tronche, Grenoble Cedex 9, France.
SP englisch
PO USA