Neuroprotective Effects of Raloxifene on Aβ_(25-35)-induced Damages in PC12 Cells via Mitogen-activated Protein Kinase Signaling Pathway  

作　　者：Xue DAI Jie WU Xue-ping SUN Li GAO Yu-gui CUI Jia-yin LIU 

机构地区：[1]Center of Clinical Reproductive Medicine,Second Affiliated Hospital of Nanjing Medical University,Nanjing 210011,China [2]Department of Obstetrics and Gynecology,First Affiliated Hospital,Nanjing Medical University,Nanjing 210029,China

出　　处：《Journal of Reproduction and Contraception》2012年第1期1-16,共16页生殖与避孕（英文版）

基　　金：supported by the "Six Talents Peak" of Jiangsu Province,China 973 Program(No.2007CB944005);Science and Technology Development Foundation of Nanjing Medical University(No.2011NJMU152)

摘　　要：Objective To investigate the neuroprotective effects and the mechanism of this protection of raloxifene （RLX）, a selective estrogen receptor modulator.Methods MTT assay and flow cytometry with annexin V-FITC/PI staining were performed to evaluate the neuroprotective effects of RLX on Aβ25-35-induced toxicity. The potential mechanisms were studied by Western blotting in cultured rat pheochromocytoma cells （PC12 cells）.Results RLX（1 000 nmol/L）, in combination with Aβ25-35 （30 llmol/L）, increased the cell viability （P 〈0.001）, and reduced the number of apoptotic cells （P 〈0.05）. RLX attenuated Aβ25-35-induced loss of △ψm （P 〈0.01）. The changing of △ψm was similar to the variation of apoptosis. PD98059 （inhibitor of ERK1/2） inhibited the effects of RLX on cell viability and phosphorylation of cleaved caspase-9. No significant difference of cell viability or phosphorylation of cleaved caspase-9 had been found when PC12 cells were incubated with SB203580 （inhibitor of p38MAPK） or SP600125 （inhibitor of JNK）. Afl25.35 induced a time-dependent phosphorylation of p38MAPK and JNK. In PC12 cells treated solely with RLX, ERK1/2 was activated （P〈0.01）. In PC12 cells treated with Aβ25-35 and RLX, Aβ2545-induced phosphorylation of p38MAPK and JNK were inhibited （P〈0.01 and P〈0.001, respectively）.Conclusion RLX inhibited Af125.35-induced cell apoptosis by activating the ERK1/2 pathway in PC12 cells. RLX also attenuated Aβ25-35-induced activation of p38MAPK and JNK. The mitochondria pathway Was involved in this inhibitory effect.Objective To investigate the neuroprotective effects and the mechanism of this protection of raloxifene （RLX）, a selective estrogen receptor modulator.Methods MTT assay and flow cytometry with annexin V-FITC/PI staining were performed to evaluate the neuroprotective effects of RLX on Aβ25-35-induced toxicity. The potential mechanisms were studied by Western blotting in cultured rat pheochromocytoma cells （PC12 cells）.Results RLX（1 000 nmol/L）, in combination with Aβ25-35 （30 llmol/L）, increased the cell viability （P 〈0.001）, and reduced the number of apoptotic cells （P 〈0.05）. RLX attenuated Aβ25-35-induced loss of △ψm （P 〈0.01）. The changing of △ψm was similar to the variation of apoptosis. PD98059 （inhibitor of ERK1/2） inhibited the effects of RLX on cell viability and phosphorylation of cleaved caspase-9. No significant difference of cell viability or phosphorylation of cleaved caspase-9 had been found when PC12 cells were incubated with SB203580 （inhibitor of p38MAPK） or SP600125 （inhibitor of JNK）. Afl25.35 induced a time-dependent phosphorylation of p38MAPK and JNK. In PC12 cells treated solely with RLX, ERK1/2 was activated （P〈0.01）. In PC12 cells treated with Aβ25-35 and RLX, Aβ2545-induced phosphorylation of p38MAPK and JNK were inhibited （P〈0.01 and P〈0.001, respectively）.Conclusion RLX inhibited Af125.35-induced cell apoptosis by activating the ERK1/2 pathway in PC12 cells. RLX also attenuated Aβ25-35-induced activation of p38MAPK and JNK. The mitochondria pathway Was involved in this inhibitory effect.

关 键 词：RALOXIFENE AΒ25-35 APOPTOSIS MAPK signaling pathway Alzheimer＇s disease mitogen-activated protein kinase （MAPK） 

分 类 号：Q987[生物学—遗传学] Q421[生物学—人类学]