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Increased Antioxidant Resistant Cells Enzyme Activity in Amyloid Protein

Clones of the rat pheochromocytoma cell line PC1 2 were selected for their resistance to amyloid p protein (A/3). These A/3-resistant cells also survive higher concentrations of exogenously applied peroxides than the parent cells. AP triggers intracellular H,O, accumulation in the parent PC12 cells but not in the AP-resistant cells. The absence of H,O, accumulation in A/+resistant cells is not attributable to differences in AP 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 AP-resistant clones. These activities correlate well with the increased resistance of cells to A/3 or peroxides. Finally, cells transfected with catalase and glutathione peroxidase are also more resistant to A/3 toxicity. These results indicate that increased antioxidant enzyme activities in AP-resistant cells account for at least pat-t of their resistance to A/3 and substantiate further the role of H,O, in AP toxicity.