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Journal of Neuroscience, Vol 16, 497-505, Copyright © 1996 by Society for Neuroscience
Increased antioxidant enzyme activity in amyloid beta protein-resistant cells
Y Sagara, R Dargusch, FG Klier, D Schubert and C Behl
Salk Institute for Biological Studies, San Diego, California 92186, USA.
Clones of the rat pheochromocytoma cell line PC12 were selected for their
resistance to amyloid beta protein (A beta). These A beta- resistant cells
also survive higher concentrations of exogenously applied peroxides than
the parent cells. A beta triggers intracellular H2O2 accumulation in the
parent PC12 cells but not in the A beta- resistant cells. The absence of
H2O2 accumulation in A beta-resistant cells is not attributable to
differences in A beta binding to the cell surface. However, the mRNA and
protein levels of catalase and glutathione peroxidase, as well as the
corresponding enzyme activities, are highly elevated in A beta-resistant
clones. These activities correlate well with the increased resistance of
cells to A beta or peroxides. Finally, cells transfected with catalase and
glutathione peroxidase are also more resistant to A beta toxicity. These
results indicate that increased antioxidant enzyme activities in A beta-
resistant cells account for at least part of their resistance to A beta and
substantiate further the role of H2O2 in A beta toxicity.
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