NR ABTA
AU Brown,D.R.; Schmidt,B.; Kretzschmar,H.A.
TI Effects of oxidative stress on prion protein expression in PC12 cells
QU International Journal of Developmental Neuroscience 1997 Dec; 15(8): 961-72
PT journal article
AB PC12 cells are known to express the prion protein, a normal cell surface glycoprotein. This protein is upregulated in PC12 cells differentiated with nerve growth factor. A neurotoxic prion protein peptide, PrP106-126, is not toxic to PC12 cells alone. PrP106-126 is toxic to PC12 cells co-cultured with microglia and more so to NGF-differentiated PC12 cells. PC12 cells selected for resistance to either copper toxicity or oxidative stress have higher levels of PrPc expression. Both PC12 variants are more sensitive to the toxicity of PrP106-126. This suggests that PC12 sensitivity to PrP106-126 toxicity is related to prion protein expression and not to a state of high differentiation induced by NGF. Variants of PC12 cells that are more resistant to copper toxicity have higher levels of anti-oxidant enzymes, superoxide dismutase and glutathione peroxidase. Our results suggest that cells expressing higher levels of PrPc have higher resistance to oxidative stress or copper toxicity but are more sensitive to PrP106-126 toxicity. Prion protein expression may be involved in both the metabolism of copper and resistance to oxidative stress. Increased cellular resistance to copper toxicity may be partly related to increased activity of anti-oxidant enzymes.
MH Animal; Glutathione Peroxidase/metabolism; Oxidative Stress/*physiology; PC12 Cells/drug effects/*metabolism; Peptide Fragments/poisoning; Prions/*metabolism/poisoning; Rats; Superoxide Dismutase/metabolism; Support, Non-U.S. Gov't
AD Institut für Neuropathologie, Universität Göttingen, Germany. drb33@cam.ac.uk
SP englisch
PO England