Involvement of oxidative stress on the impairment of energy
metabolism induced by A beta peptides on PC12 cells: protection by
Pereira C, Santos MS, Oliveira C.
Faculty of Medicine,
University of Coimbra, Portugal.
Neurobiol Dis 1999 Jun;6(3):209-19
- Alzheimer's disease is widely held to be associated
with oxidative stress due, in part, to the membrane action of amyloid
beta-peptide (A beta) aggregates. In this study, the involvement of
oxidative stress on A beta-induced energy metabolism dysfunction was
evaluated on PC12 cells. It was shown that A beta peptides (A
beta25-35 and A beta1-40) induce a concentration-dependent accumulation of
reactive oxygen species (ROS), decrease the cellular redox activity, and
lead to the depletion of ATP levels. The observed inhibition 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
impairment 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.