Increased antioxidant enzyme activity in amyloid beta protein-resistant cells.
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.
Sagara
Y
Y
Salk Institute for Biological Studies, San Diego, California 92186, USA.
Dargusch
R
R
Klier
F G
FG
Schubert
D
D
Behl
C
C
D000544:Alzheimer Disease / Q000201:enzymology; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D002374:Catalase / Q000378:metabolism; D002478:Cells, Cultured; D005979:Glutathione Peroxidase / Q000378:metabolism; D008854:Microscopy, Electron; D016716:PC12 Cells / Q000201:enzymology* / Q000648:ultrastructure; D051381:Rats
D016564:Amyloid beta-Protein Precursor; D000975:Antioxidants; D002374:Catalase; D005979:Glutathione Peroxidase