Objective To investigate whether JNK-caspase-dependent apoptotic pathway is involved in Aβ31-35-induced apoptosis of cultured cortical neurons. Methods Cultured cortical neurons were treated with Aβ31-35 （25 μmol/...Objective To investigate whether JNK-caspase-dependent apoptotic pathway is involved in Aβ31-35-induced apoptosis of cultured cortical neurons. Methods Cultured cortical neurons were treated with Aβ31-35 （25 μmol/L） for 4 h, 8 h, 16 h and 24 h, respectively. Caspase activities were measured using a spectrophotometer. Levels of c-Jun phosphorylation （p-c-Jun） and Fas ligand （FasL） expression were assessed by immunocytochemistry method and quantified using Image-pro plus11.0 image processing and analysis software. Results Treatment with Aβ31-35 （25 μmol/L） for 24 h induced significant increases in the activities of caspase-3 and caspase-8 in the cortical neurons. Besides, Aβ31-35 could time-dependently enhance the expression of p-c-Jun protein. Moreover, SP600125 application （100 nmol/L） could completely abolish Aβ31-35 neurotoxicity. The increase in FasL expression was detected at 8 h, 16 h and 24 h after Aβ31-35 treatment, and SP600125 （100 nmol/L） significantly inhibited FasL expression. Conclusion JNK-c-Jun-FasL-caspase-dependent extrinsic apoptotic pathway plays a critical role in mediating Aβ31-35-induced apoptosis of cultured neurons.展开更多
基金supported by the National Natural Science Foundation of China (No. 30572085)Natural Science Foundation of Shanxi Province, China(No. 2007011111)
文摘Objective To investigate whether JNK-caspase-dependent apoptotic pathway is involved in Aβ31-35-induced apoptosis of cultured cortical neurons. Methods Cultured cortical neurons were treated with Aβ31-35 （25 μmol/L） for 4 h, 8 h, 16 h and 24 h, respectively. Caspase activities were measured using a spectrophotometer. Levels of c-Jun phosphorylation （p-c-Jun） and Fas ligand （FasL） expression were assessed by immunocytochemistry method and quantified using Image-pro plus11.0 image processing and analysis software. Results Treatment with Aβ31-35 （25 μmol/L） for 24 h induced significant increases in the activities of caspase-3 and caspase-8 in the cortical neurons. Besides, Aβ31-35 could time-dependently enhance the expression of p-c-Jun protein. Moreover, SP600125 application （100 nmol/L） could completely abolish Aβ31-35 neurotoxicity. The increase in FasL expression was detected at 8 h, 16 h and 24 h after Aβ31-35 treatment, and SP600125 （100 nmol/L） significantly inhibited FasL expression. Conclusion JNK-c-Jun-FasL-caspase-dependent extrinsic apoptotic pathway plays a critical role in mediating Aβ31-35-induced apoptosis of cultured neurons.
