Upregulation of Heme Oxygenase-1 by Acteoside Through ERK and PI3 K/Akt Pathway Confer Neuroprotection Against Beta-Amyloid-Induced Neurotoxicity
Upregulation of Heme Oxygenase-1 by Acteoside Through ERK and PI3 K/Akt Pathway Confer Neuroprotection Against Beta-Amyloid-Induced Neurotoxicity
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Acteoside 通过 ERK 和 PI3 K/Akt 途径上调血红素加氧酶 1，从而提供针对 β-淀粉样蛋白诱导的神经毒性的神经保护作用
DOI：
10.1007/s12640-011-9292-5
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发表时间：
2012-05-01
影响因子：
3.7
通讯作者：
Zhu, Cui-Qing
中科院分区：
文献类型：
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作者：
Wang, Hong-Quan;Xu, Yu-Xia;Zhu, Cui-Qing
我们以前的研究表明，类叶升麻苷，一种抗氧化的苯乙醇苷，在体外保护β-淀粉样蛋白（A β）诱导的细胞毒性。然而，确切的保护机制仍不清楚。血红素氧合酶-1（HO-1）是对氧化损伤的反应中的关键因子，保护神经元免受A β诱导的损伤。在本研究中，我们研究确定毛蕊花苷是否上调HO-1表达，从而保护PC 12细胞免受A β诱导的细胞死亡。结果表明，类叶升麻苷是Nrf2的激活剂和HO-1表达的诱导剂。我们发现，类叶升麻苷增加HO-1的表达在体外和体内。麦角甾苷处理导致转录因子NF-E2相关因子2（Nrf2）的核转位。麦角甾苷激活ERK和PI3 K/Akt，并且用特异性ERK抑制剂PD98059、PI3 K抑制剂LY294002和特异性Nrf2 siRNA处理抑制麦角甾苷诱导的HO-1表达。HO-1抑制剂ZnPP、PD 98059和LY 294002明显消除了毛蕊花苷对A β诱导的神经毒性的神经保护作用。综上所述，这些结果表明类叶升麻苷是Nrf2的激活剂和HO-1表达的诱导剂。我们还发现类叶升麻苷通过激活ERK和PI3K/Akt信号通路增加HO-1的表达。毛蕊花糖苷上调HO-1可能参与了A β诱导的神经毒性的神经保护作用。
Our previous study has shown that acteoside, an antioxidative phenylethanoid glycoside, protect against beta-amyloid (A beta)-induced cytotoxicity in vitro. However, the precise protective mechanisms remains unclear. Heme oxygenase-1 (HO-1) is a crucial factor in the response to oxidative injury, protecting neurons against A beta-induced injury. In the present study we examined to determine whether acteoside upregulates HO-1 expression, and thereby protects PC12 cells against A beta-induced cell death. It was revealed that acteoside is an activator of Nrf2 and inducer of HO-1 expression. We showed that acteoside increased HO-1 expression in vitro and in vivo. Acteoside treatment resulted in nuclear translocation of the transcription factor NF-E2-related factor 2 (Nrf2). Acteoside activated both ERK and PI3 K/Akt, and treatments with the specific ERK inhibitor PD98059, the PI3 K inhibitor LY294002, and the specific Nrf2 siRNA suppressed the acteoside-induced HO-1 expression. The HO-1 inhibitor ZnPP, PD98059, and LY294002 markedly abolished the neuroprotective effect of acteoside against A beta-induced neurotoxicity. Taken together, these results demonstrate that acteoside is an activator of Nrf2 and inducer of HO-1 expression. We also showed that acteoside increased HO-1 expression through activation of ERK and PI3 K/Akt signal pathways in vitro. Upregulation of HO-1 by acteoside may involve in the neuroprotection against A beta-induced neurotoxicity.