Shanghai Medical College, Fudan University, Shanghai 200032, People's Republic of China.
Brain Res. 2010 Nov 11;1360:159-67. doi: 10.1016/j.brainres.2010.08.100. Epub 2010 Sep 7.
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 Aβ(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 Aβ(25-35)-induced cytotoxicity in SH-SY5Y cells. Pre-treatment with ATX for 4h significantly reduced the Aβ(25-35)-induced viability loss, apoptotic rate and attenuated Aβ-mediated ROS production. In addition, ATX inhibited Aβ(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 Aβ. 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 Aβ(25-35)-induced injury. Because the inhibitor of HO-1 activity, ZnPP reversed the protective effect of ATX against Aβ(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 Aβ25-35-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 Aβ(25-35)-induced oxidative cell death.
虾青素（ATX）是蜂胶中含量最丰富的类黄酮，已被证明具有抗谷氨酸诱导的神经毒性和缺血再灌注诱导的细胞凋亡的神经保护特性。先前的研究表明，ATX 可以挽救 PC12 细胞免受 Aβ（25-35）诱导的凋亡死亡。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 SH-SY5Y 细胞中 Aβ（25-35）诱导的细胞毒性的保护作用的潜在机制。用 ATX 预处理 4 小时可显著降低 Aβ（25-35）诱导的活力丧失、凋亡率，并减轻 Aβ 介导的 ROS 产生。此外，ATX 抑制 Aβ（25-35）诱导的降低膜电位，减少 Bcl-2/Bax 比值。我们还表明，ATX 可以防止 Aβ 诱导的 p38MAPK 激酶途径的激活。此外，我们首次揭示 ATX 以浓度和时间依赖的方式增加抗氧化酶血红素加氧酶-1（HO-1）的表达，这与其对 Aβ（25-35）诱导损伤的保护作用相关。HO-1 活性抑制剂 ZnPP 逆转了 ATX 对 Aβ（25-35）诱导的细胞死亡的保护作用。我们还表明，特异性 ERK 抑制剂 PD98059 浓度依赖性地阻断 ATX 诱导的 HO-1 表达，同时 PD98059 逆转了 ATX 对 Aβ25-35 诱导的细胞死亡的保护作用。总之，这些发现表明虾青素可以通过激活 ERK 信号通路诱导 HO-1 表达，从而保护 SH-SY5Y 细胞免受 Aβ（25-35）诱导的氧化细胞死亡。
