雷洛昔芬通过调节端粒酶活性抑制Aβ所致神经细胞凋亡

Raloxifene Attenuates A β-induced Apoptosis in ER α-Transfected PC12 Cells by Increasing the Telomerase Activity

目的:探讨雷洛昔芬是否具有类似于雌激素对转染了雌激素受体estrogen receptor(ER)α的PC12细胞有保护作用,即对抗淀粉样蛋白Aβ所致细胞凋亡及活化端粒酶活性.方法:在转染了雌激素受体ERα的PC12细胞(PCER)及转染了对照基因质粒的PC12细胞(PCCON)中分别添加不同的药物.用TUNEL染色法观察细胞凋亡情况;stretch PCR试剂盒分析端粒酶的活性.结果:在经过Aβ处理后的PCER中添加10-8 M雷洛昔芬与10-8 M雌激素后细胞凋亡数显著减少,而在PCCON中则无明显差异;雌激素和雷洛昔芬对PCER细胞显著促进其端粒酶活性,对PCCON细胞无此作用.结论:雷洛昔芬与雌激素对有雌激素受体表达的PC12细胞均有活化端粒酶活性,抑制淀粉样蛋白Aβ诱发的细胞凋亡作用,表明雌激素和雷洛昔芬抑制Aβ所致细胞凋亡的作用是通过雌激素受体ERα来实现的.

Objective： To investigate whether raloxifene similar to estrogen（E2）,exhibit cytoprotection effect on PC12 cells tranfected with estrogen receptor（ER）α,that is against amyloid beta protein（Aβ）induced apoptosis and increase telomerase activity.Methods： PC12 cells were transfected with the full-length human ER-gene（PCER） or with vector DNA alone（PCCON）,some cells were treated with various drugs.Apoptosis was assessed by Tunnel staining.Stretch PCR assays were performed for quantitative analysis of telomerase activity.Results： PCER and PCCON cells pretreated with Aβ,then incubated with 10-8 M E2 or 10-8 M raloxifene.Both E2 and raloxifene attenuate the A-induced apoptosis and increase the telomerase activity.While PCCON cells did not.Significant differences are indicated.Conclusion： Both estogen and raloxifene attenuate the A-induced apoptosis in estrogen receptor（ER）α-transfected PC12 cells by activation of telomerase activity.They attenuate the A-induced apoptosis via estrogen receptor.