INCREASED ANTIOXIDANT ENZYME-ACTIVITY IN AMYLOID-BETA PROTEIN-RESISTANT CELLS

Clones of the rat pheochromocytoma cell line PC12 were selected for th eir resistance to amyloid beta protein (A beta). These A beta-resistan t cells also survive higher concentrations of exogenously applied pero xides than the parent cells. A beta triggers intracellular H2O2 accumu lation 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 att ributable to differences in A beta binding to the cell surface. Howeve r, the mRNA and protein levels of catalase and glutathione peroxidase, as well as the corresponding enzyme activities, are highly elevated i n A beta-resistant clones. These activities correlate well with the in creased resistance of cells to A beta or peroxides. Finally, cells tra nsfected with catalase and glutathione peroxidase are also more resist ant to A beta toxicity. These results indicate that increased antioxid ant enzyme activities in A beta-resistant cells account for at least p art of their resistance to A beta and substantiate further the role of H2O2 in A beta toxicity.