Astaxanthin upregulates heme oxygenase-1 expression through ERK1/2 pathway and its protective effect against beta-amyloid-induced cytotoxicity in SH-SY5Y cells
Astaxanthin upregulates heme oxygenase-1 expression through ERK1/2 pathway and its protective effect against beta-amyloid-induced cytotoxicity in SH-SY5Y cells
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虾青素通过 ERK1/2 途径上调血红素加氧酶 1 表达及其对 SH-SY5Y 细胞中 β-淀粉样蛋白诱导的细胞毒性的保护作用
DOI：
10.1016/j.brainres.2010.08.100
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发表时间：
2010-11-11
期刊：
影响因子：
2.9
通讯作者：
Zhu, Cui-Qing
中科院分区：
文献类型：
--
作者：
Wang, Hong-Quan;Sun, Xiao-Bo;Zhu, Cui-Qing
虾青素(ATX)是蜂胶中含量最丰富的黄酮类化合物，已被证明对谷氨酸诱导的神经毒性和缺血再灌注诱导的细胞凋亡具有神经保护作用。先前的研究表明，ATX可以从Aβ(25-35)诱导的凋亡死亡中拯救PC12细胞。然而，ATX在体外介导其治疗作用的机制尚不清楚。在本研究中，我们探讨了ATX对Aβ(25-35)诱导的SH-SY5Y细胞毒性的保护作用的机制。ATX预处理4h可显著降低Aβ(25-35)诱导的细胞存活率、凋亡率和抑制Aβ介导的ROS的产生。此外，ATX还可抑制Aβ(25-35)所致的膜电位降低，降低Bcl2/Bax比值。我们还证实了ATX可以阻止Aβ诱导的p38MAPK通路的激活。此外，我们首次发现ATX以浓度依赖和时间依赖的方式增加抗氧化酶HO-1的表达，这与其对Aβ(25-35)诱导的损伤的保护作用有关。由于是HO-1活性的抑制者，锌锌蛋白逆转了ATX对Aβ(25-35)诱导的细胞死亡的保护作用。我们还证实了特异性ERK抑制剂PD98059浓度依赖地阻断ATX诱导的HO-1的表达，同时PD98059逆转了ATX对Aβ(25-35)诱导的细胞死亡的保护作用。综上所述，这些发现表明虾青素可以通过激活ERK信号通路来诱导HO-1的表达，从而保护SH-SY5Y细胞免受Aβ(25-35)诱导的细胞氧化死亡。(C)2010爱思唯尔B.V.保留所有权利。
Astaxanthin (ATX), the most abundant flavonoids in propolis, has been proven to exert neuroprotective property against glutamate-induced neurotoxicity and ischemia-reperfusion-induced apoptosis. Previous study have revealed that ATX can rescue PC12 cells from A beta(25-35)-induced apoptotic death. However, the mechanisms by which ATX mediates its therapeutic effects in vitro are unclear. In the present study, we explored the underlying mechanisms involved in the protective effects of ATX on the A beta(25-35)-induced cytotoxicity in SH-SY5Y cells. Pre-treatment with ATX for 4 h significantly reduced the A beta(25-35)-induced viability loss, apoptotic rate and attenuated A beta-mediated ROS production. In addition, ATX inhibited A beta(25-35)-induced lowered membrane potential, decreased Bcl-2/Bax ratio. We also demonstrated that ATX could prevent the activation of p38MAPK kinase pathways induced by A beta. Moreover, we for the first time have revealed the ATX increased antioxidant enzyme heme oxygenase-1 (HO-1) expression in concentration-dependent and time-dependent manners, which were correlated with its protective effect against A beta(25-35)-induced injury. Because the inhibitor of HO-1 activity, ZnPP reversed the protective effect of ATX against A beta(25-35)-induced cell death. We also demonstrated that the specific ERK inhibitor, PD98059, concentration-dependently blocked on ATX-induced HO-1 expression, and meanwhile PD98059 reversed the protective effect of ATX against A beta(25-35)-induced cell death. Taken together, these findings suggest that astaxanthin can induce HO-1 expression through activation of ERK signal pathways, thereby protecting the SH-SY5Y cells from A beta(25-35)-induced oxidative cell death. (C) 2010 Elsevier B.V. All rights reserved.