Involvement of oxidative stress on the impairment of energy metabolism induced by A beta peptides on PC12 cells: Protection by antioxidants

Alzheimer's disease is widely held to be associated with oxidative stress d ue, in part, to the membrane action of amyloid beta-peptide (A beta) aggreg ates. In this study, the involvement of oxidative stress on A beta-induced energy metabolism dysfunction was evaluated on PC12 cells. It was shown tha t A beta peptides (A beta 25-35 and A beta 1-40) induce a concentration-dep endent accumulation of reactive oxygen species (ROS), decrease the cellular redox activity, and lead to the depletion of ATP levels. The observed inhi bition by A beta of mitochondrial function and of glycolysis is blocked by the antioxidants vitamin E, idebenone, and GSH ethyl ester. Taken together, these data suggest that exposure of PC12 cells to A beta results in an imp airment of energy metabolism, leading to a deficit in ATP levels and to the compromise of cellular viability. Furthermore, the generation of ROS seems to be a crucial event responsible for the energetic metabolic dysfunction induced by A beta. (C) 1999 Academic Press.