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 rea...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.展开更多
Chromatin is the primary carrier of epigenetic information in higher eukaryotes. AtCYP71 contains both cyclophilin domain and WD40 repeats. Loss of AtCYP71 function causes drastic pleiotropic phenotypic defects. Here,...Chromatin is the primary carrier of epigenetic information in higher eukaryotes. AtCYP71 contains both cyclophilin domain and WD40 repeats. Loss of AtCYP71 function causes drastic pleiotropic phenotypic defects. Here, we show that AtCYP71 physically interacts with FAS1 and LHP1, respectively, to modulate their distribution on chromatin. The Ihpl cyp71 double mutant showed more severe phenotypes than the single mutants, suggesting that AtCYP71 and LHP1 synergistically control plant development. Such synergism was in part illustrated by the observation that LHP1 association with its specific target loci requires AtCYP71 function. We also demonstrate that AtCYP71 physically interacts with FAS1 and is indispensable for FAS1 targeting to the KNAT1 locus. Together, our data suggest that AtCYP71 is involved in fundamental processes of chromatin assembly and histone modification in plants.展开更多
文摘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.
文摘Chromatin is the primary carrier of epigenetic information in higher eukaryotes. AtCYP71 contains both cyclophilin domain and WD40 repeats. Loss of AtCYP71 function causes drastic pleiotropic phenotypic defects. Here, we show that AtCYP71 physically interacts with FAS1 and LHP1, respectively, to modulate their distribution on chromatin. The Ihpl cyp71 double mutant showed more severe phenotypes than the single mutants, suggesting that AtCYP71 and LHP1 synergistically control plant development. Such synergism was in part illustrated by the observation that LHP1 association with its specific target loci requires AtCYP71 function. We also demonstrate that AtCYP71 physically interacts with FAS1 and is indispensable for FAS1 targeting to the KNAT1 locus. Together, our data suggest that AtCYP71 is involved in fundamental processes of chromatin assembly and histone modification in plants.
