Qiaoling Peng, Amber R. Buz’Zard, Benjamin H. S. Lau
Med Sci Monit 2002; 8(8): BR328-337
Available online: 2002-08-07
Background: Neuronal apoptosis is one of the pathological features of Alzheimer’s disease (AD) and is associated with senile plaques containing amyloid-β peptide (Aβ). Reactive oxygen species (ROS)
are proposed to be involved in the apoptotic mechanism of Aβ-mediated neurotoxicity. The purpose of this study was to determine the effects of aged garlic extract (AGE) and S-allyl cysteine
(SAC) on Aβ25-35-induced apoptosis and ROS generation in a rat pheochromocytoma (PC12) cell line.
Material/Methods: PC12 cells were grown in RPMI 1640 medium containing 5% fetal calf serum and 10% horse serum. Cells were incubated with AGE or SAC for 24 h prior to exposure to Aβ25-35 for various times. Cell viability, DNA fragmentation, number of apoptotic cells, caspase activity and generation of ROS were determined.
Results: Aβ25-35–induced apoptosis in PC12 cells was demonstrated by: 1) A dose-dependent loss of cell viability; 2) A time- and dose-dependent increase in apoptotic cells; 3) An induction of DNA
fragmentation; and 4) An increase in caspase-3 activity and cleavage of poly (ADP—ribose) polymerase (PARP). After exposing PC12 cells to Aβ25-35, a significant increase in ROS preceded apoptotic events. AGE and SAC not only suppressed the generation of ROS but also attenuated caspase-3 activation, DNA fragmentation, PARP cleavage and eventually protected against Aβ-induced apoptosis.
Conclusions: Our data suggest that ROS may be involved in Aβ-induced apoptosis in PC12 cells. They further suggest that garlic compounds can reduce apoptosis, possibly by enhancing the endogenous antioxidant defenses.
Keywords: Alzheimer Disease - metabolism