[Effect of Chinese herb Tripterygium wilfordii Hook F monomer triptolide on apoptosis of PC12 cells induced by Abeta1-42].
Recent studies indicate that beta-amyloid (Abeta) is the key factor to cause neuronal degeneration in Alzheimer's disease (AD). In the present study, we set up an Abeta induced PC12 cell damage modle and studied the protective effect and related mechanisms of T(10), monomer extracted from Chinese herb Tripterygium wilfordii Hook F. PC12 cells were treated with different concentrations of Abeta (5x10(-4), 5x10(-3), 5x10(-2), 5x10(-1), 5, 50 micromol/L) for 48 h, cell viability was detected by MTT conversion. The apoptotic rate of PC12 cells was quantitatively determined using FACS assay. After PC12 cells were treated with 1x10(-11) mol/L T(10) for 48 h and then co-treated with 50 micromol/LAbetafor 48 h, the apoptotic rate and the change in intracellular Ca(2+) concentration of PC12 cells were analyzed by FACS assay and confocal, respectively. It was found that 5 micromol/L Abeta decreased the cell viability to 66.3% and 50 micromol/L Abeta decreased it to 55.1%, significantly different from that of the control group. After treatment with 50 micromol/L Abeta for 48 h, the apoptotic rate of PC12 cells increased obviously. The apoptotic rate was 5.37% in the control group, while after treatment with 0.5, 5 and 50 micromol/L Abeta for 48 h, the apoptotic rate of PC12 cells went up to 10.19%, 8.02% and 16.63%, respectively. At the same time, the concentration of intracellular Ca(2+) increased greatly after treatment with 50 micromol/L Abeta for 48 h. At the concentration of 1x10(-11) mol/L T(10) remarkably inhibited the apoptosis induced by 50 micromol/L Abeta. In the naive group, the apoptotic rate was 4.83%. The apoptotic rate went up to 17.24% after treatment with 50 micromol/L Abeta for 48 h. After co-treatment with 1x10(-11) mol/L T(10) and 50 micromol/L Abeta, the apoptotic rate decreased to 8.91%, significantly different from that of the control group. At the same time, at the concentration of 1x10(-11 )mol/L T(10) remarkably inhibited the increase of intracellular Ca(2+) concentration induced by Abeta. The results indicate that T(10) has obvious protective effect on PC12 cells, which may be related to the inhibition of the cell apoptosis and increment of intracellular Ca(2+) concentration induced by Abeta.
Gu
Ming
M
Neuroscience Research Institute, Peking University, Beijing 100083, China.
Zhou
Hui-Fang
HF
Xue
Bing
B
Niu
Dong-Bin
DB
He
Qi-Hua
QH
Wang
Xiao-Min
XM
D000544:Alzheimer Disease / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism; D004224:Diterpenes / Q000494:pharmacology*; D004852:Epoxy Compounds; D018696:Neuroprotective Agents / Q000494:pharmacology; D016716:PC12 Cells; D010446:Peptide Fragments / Q000633:toxicity*; D010616:Phenanthrenes / Q000494:pharmacology*; D051381:Rats; D029757:Tripterygium / Q000737:chemistry*
D016229:Amyloid beta-Peptides; D004224:Diterpenes; D004852:Epoxy Compounds; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D010616:Phenanthrenes; C075222:amyloid beta-protein (1-42); C001899:triptolide; D002118:Calcium