NR ANFP
AU Rachidi,W.; Vilette,D.; Guiraud,P.; Arlotto,M.; Riondel,J.; Laude,H.; Lehmann,S.; Favier,A.
TI Expression of prion protein increases cellular copper binding and antioxidant enzyme activities but not copper delivery
QU The Journal of Biological Chemistry 2003 March 14; 278(11): 9064-9072
PT journal article
AB The N-terminal region of the prion protein PrPc contains a series of octapeptide repeats. This region has been implicated in the binding of divalent metal ions, particularly copper. PrPc has been suggested to be involved in copper transport and metabolism and in cell defence mechanisms against oxidative insult, possibly through the regulation of the intracellular Cu/Zn superoxide dismutase activity (Cu/Zn-SOD) or a SOD-like activity of PrPc itself. However, up to now the link between PrPc expression and copper metabolism or SOD activity has still to be formally established, particularly because conflicting results have been obtained in vivo. In this study, we report a link between PrPc, Cu binding and resistance to oxidative stress. Radioactive copper (64Cu) was used at a physiological concentration to demonstrate that binding of copper to the outer of the plasma cell membrane is related to the level of PrPc expression in a cell line expressing a doxycycline inducible murine PrPc gene. Cell PIPLC pre-treatment indicated that PrPc was not involved in Cu delivery at physiological concentration. We also demonstrated that murine PrPc expression increases several antioxidant enzymes activities and glutathione levels. Prion protein may be a stress sensor sensitive to copper and able to initiate, following copper binding, a signal transduction process acting on the antioxidant systems to improve the cell defences.
AD Biochemistry Dept., Universit Joseph Fourier, La Tronche 38706.
SP englisch