Protective effect of cyclophilin A against Alzheimer's amyloid beta-peptide (25-35)-induced oxidative stress in PC12 cells.
BACKGROUND
beta-amyloid peptide (Abeta) is considered responsible for the pathogenesis of Alzheimer's disease (AD). Possible mechanisms underlying Abeta-induced neuronal cytotoxicity include excessive production of reactive oxidative species (ROS) and apoptosis. Cyclophilin A (CypA), exhibits antioxidant properties and protects neurons against oxidative stress induced injury. This study was conducted to demonstrate whether CyPA added to cultured PC12 cells could alleviate Abeta-induced oxidative stress and protect them from apoptosis.


METHODS
PC12 cells were pre-incubated for 30 minutes with recombinant human cyclophilin A (rhCyPA) in 0.1 nmol/L, 1.0 nmol/L, 10 nmol/L and 100 nmol/L and then incubated with 10 micromol/L Abeta(25-35). In every group, cell viability, apoptotic morphology, apoptotic rate, intracellular ROS accumulation, the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) of PC12 cells and mitochondrial transmembrane potential were detected. Subsequently, the expression of the active form of caspase-3 was determined by Western blotting.


RESULTS
It was shown that cultures treated with 1.0 nmol/L, 10 nmol/L or 100 nmol/L rhCyPA + Abeta(25-35) had significantly higher cell viability and a lower rate of apoptosis compared with the cultures exposed only to Abeta(25-35). In addition, rhCyPA attenuated Abeta(25-35)-induced overproduction of intracellular ROS and Abeta(25-35)-induced a decrease in activity of the key antioxidant enzymes SOD and GSH-Px. Furthermore, rhCyPA also attenuated Abeta(25-35)-induced mitochondrial dysfunction and the activation of caspase-3.


CONCLUSIONS
CyPA may act as an ROS scavenger, and prevent Abeta(25-35)-induced neurotoxicity through attenuating oxidative stress induced by Abeta(25-35).
Ge
Yu-Song
YS
Department of Neurology, First Affiliated Hospital, China Medical University, Shenyang, Liaoning 110001, China.
Teng
Wei-Yu
WY
Zhang
Chao-Dong
CD