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二苯乙烯苷通过激活Nrf2减轻MPP+诱导的PC12细胞凋亡
TSG Attenuats MPP+-induced Apoptosis in PC12 Cells by the Activation of Nrf2
目的 研究2,3,5,4′-四羟基二苯乙烯-2-O-β-D-葡萄糖苷( 2,3,5,4′-tetrahydroxystibene-2-O-β-D-glucoside,TSG)对1-甲基-4-苯基吡啶离子(1-methy-4-phenylpyridinium;MPP+)诱导PC12细胞凋亡的影响及其可能机制。方法 4-甲基偶氮唑蓝(MTT)检测PC12细胞活性; Hochest 33258染色观察细胞凋亡的变化; DCFH-DA/DAF-FM DA检测ROS/NO表达情况;Westernblotting检测Nrf2、Keap1、SOD1、SOD2、CAT蛋白的表达情况。结果 MPP+(500 μmol·L-1)作用于PC12细胞24 h后,与正常组比较,细胞存活率降低至(51.3±2.2)%(P<0.01);TSG(10,50 μmol·L-1)预处理24 h后,细胞存活率增加至(60.1±1.5)%,(74.2±2.1)%,(82.1±1.5)%(P<0.05);细胞核固缩明显减少,且具有剂量依赖性关系。此外,MPP+处理后使PC12细胞中ROS/NO升高,Nrf2、SOD1、SOD2、CAT蛋白表达减少,使keap1表达增多,而TSG预处理可以明显改善这些变化。结论 TSG对MPP+诱导的PC12细胞凋亡具有浓度依赖性的抑制作用,其作用机制可能通过激活Nrf2/Keap1通路减轻细胞内活性氧的聚集有关。
OBJECTIVE To explore the protective effect of 2,3,5,4′-tetrahydroxystibene-2-O-β-D-glucoside(TSG) on 1-methy-4-phenylpyridinium(MPP+) induced apoptosis in PC12 cells and its possible mechanism.METHODS The cell viability was measured by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide(MTT).The morphological change of PC12 cells was observed by Hoechst 33258 staining.The intracellular ROS/NO level was examined by using DCFH-DA/DAF-FM DA. The expression level of Nrf2, Keap1, SOD1, SOD2, CAT protein was detected by Western blotting.RESULTS Compared with the control group,the ratio of cell survival decreased to (51.3±2.2)% (P<0.01) after MPP+ treatment with PC12 cells for 24 h.Cell viability was increased to(60.1±1.5)%,(74.2±2.1)%, (82.1±1.5)% (P<0.05) respectively after exposure with 10, 50 μmol·L-1 TSG.Cytochromatin concentration reduced and show the relation between quantity and result.Furthermore, TSG inhibited the MPP+-induced increase reactive oxygen species/nitric oxide (ROS/NO) in PC12 cell, and counteracted the over expression of Keap1 and low-expression of Nrf2, SOD1, SOD2, CAT.CONCLUSION TSG plays a possible neuroprotective role in MPP+ induced apoptosis of PC12 cells by a concentration-dependent manner, and the mechanism of the effects of TSG may be involved in facilitating Nrf2/keap1 activation.
二苯乙烯苷 / 凋亡 / Nrf2 / PC12细胞 {{custom_keyword}} /
TSG / apoptosis / Nrf2 / PC12 cell {{custom_keyword}} /
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国家自然科学基金资助项目(30772743)
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