Protective effect of cyclophilin A against Alzheimer＇s amyloid beta-peptide （25-35）-induced oxidative stress in PC12 cells

Background β-amyloid peptide （Aβ） is considered responsible for the pathogenesis of Alzheimer＇s disease （AD）. Possible mechanisms underlying Aβ-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 Aβ-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 μmol/L Aβ25-35. 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, 1U nmol/L or 100 nmol/L rnL, rhCyPA＋Aβ25-35 had significantly higher cell viability and a lower rate of apoptosis compared with the cultures exposed only to Aβ25-35. In addition, rhCyPA attenuated Aβ25-35-induced overproduction of intracellular ROS and Aβ25.35-induced a decrease in activity of the key antioxidant enzymes SOD and GSH-Px. Furthermore, rhCyPA also attenuated Aβ25.35-induced mitochondrial dysfunction and the activation of caspase-3.
Conclusion CyPA may act as an ROS scavenger, and prevent Aβ25-35-induced neurotoxicity through attenuating oxidative stress induced by Aβ25-35.

Protective effect of cyclophilin A against Alzheimer's amyloid beta-peptide (25-35)-induced oxidative stress in PC12 cells

Background β-amyloid peptide (Aβ) is considered responsible for the pathogenesis of Alzheimer's disease (AD). Possible mechanisms underlying Aβ-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 Aβ-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 umol/L Aβ25-35. 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 + Aβ25-35 had significantly higher cell viability and a lower rate of apoptosis compared with the cultures exposed only to Aβ25-35. In addition, rhCyPA attenuated Aβ25-35-induced overproduction of intracellular ROS and Aβ25-35-induced a decrease in activity of the key antioxidant enzymes SOD and GSH-Px. Furthermore, rhCyPA also attenuated Aβ25-35-induced mitochondrial dysfunction and the activation of caspase-3.Conclusion CyPA may act as an ROS scavenger, and prevent Aβ25-35-induced neurotoxicity through attenuating oxidative stress induced by Aβ25-35.