Neuroprotective effect of garlic compounds in amyloid-beta peptide-induced apoptosis in vitro.
BACKGROUND
Neuronal apoptosis is one of the pathological features of Alzheimer's disease (AD) and is associated with senile plaques containing amyloid-b peptide (Abeta). Reactive oxygen species (ROS) are proposed to be involved in the apoptotic mechanism of Abeta-mediated neurotoxicity. The purpose of this study was to determine the effects of aged garlic extract (AGE) and S-allyl cysteine (SAC) on Abeta(25-35)-induced apoptosis and ROS generation in a rat pheochromocytoma (PC12) cell line.


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 Abeta(25-35) for various times. Cell viability, DNA fragmentation, number of apoptotic cells, caspase activity and generation of ROS were determined.


RESULTS
Abeta(25-35)-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 Abbeta(25-35), 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 Ab-induced apoptosis.


CONCLUSIONS
Our data suggest that ROS may be involved in Ab-induced apoptosis in PC12 cells. They further suggest that garlic compounds can reduce apoptosis, possibly by enhancing the endogenous antioxidant defenses.
Peng
Qiaoling
Q
Division of Microbiology and Molecular Genetics, School of Medicine, Loma Linda University, Loma Linda, CA 92350, USA.
Buz'Zard
Amber R
AR
Lau
Benjamin H S
BH
D000544:Alzheimer Disease / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002470:Cell Survival; D003545:Cysteine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D053938:DNA Fragmentation; D004789:Enzyme Activation; D005737:Garlic / Q000737:chemistry*; D006801:Humans; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress; D016716:PC12 Cells; D010446:Peptide Fragments / Q000494:pharmacology*; D010936:Plant Extracts / Q000494:pharmacology*; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D011506:Proteins / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism
D016229:Amyloid beta-Peptides; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D010936:Plant Extracts; D011506:Proteins; D017382:Reactive Oxygen Species; C074636:amyloid beta-protein (25-35); C065299:S-allylcysteine; C499320:PARP1 protein, human; C499322:Parp1 protein, rat; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; C505407:CASP3 protein, human; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases; D003545:Cysteine