Department of Neurology, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, Shaanxi, China.
Department of Pediatrics, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, Shaanxi, China.
Life Sci. 2019 Mar 15;221:259-266. doi: 10.1016/j.lfs.2019.02.025. Epub 2019 Feb 13.
Edaravone potentially alleviates cognitive deficits in a mouse model of Alzheimer's disease (AD). However, the mechanism of edaravone in suppressing AD progression remains unclear. We aim to investigate the mechanism of edaravone in suppressing oxidative stress-mediated AD progression in vitro.
Human neuroblastoma SH-SY5Y cells were pretreated with different concentrations of edaravone prior to the induction by Aβ. Cell viability, apoptosis, reactive oxygen species, and expression of antioxidative response elements (ARE) including Nrf2, SOD, and HO-1 were assessed.
The results showed that apoptosis and reactive oxygen species levels significantly increased in Aβ-treated cells, whereas the mRNA and protein levels of Nrf2, SOD and HO-1 decreased. The opposite changes were observed in cells that were pre-treated with edaravone, particularly at a concentration of 40 μM. Aβ-treatment suppressed Nrf2 expression and nuclear translocation were rescued by Edaravone. Genetic inhibition of Nrf2 greatly decreased the protective effect of edaravone against cell apoptosis and cytotoxicity induced by Aβ, accompanied by decreases in SOD and HO-1 expression.
Activation of the Nrf2/ARE signaling pathway may underlie the protective effects of edaravone against the oxidative damage associated with Alzheimer's disease.
依达拉奉可能减轻阿尔茨海默病（AD）小鼠模型的认知缺陷。然而，依达拉奉抑制 AD 进展的机制尚不清楚。我们旨在研究依达拉奉在体外抑制氧化应激介导的 AD 进展的机制。
在 Aβ诱导前，用不同浓度的依达拉奉预处理人神经母细胞瘤 SH-SY5Y 细胞。评估细胞活力、细胞凋亡、活性氧和抗氧化反应元件（ARE）的表达，包括 Nrf2、SOD 和 HO-1。
结果表明，Aβ 处理的细胞中细胞凋亡和活性氧水平显著增加，而 Nrf2、SOD 和 HO-1 的 mRNA 和蛋白水平降低。用依达拉奉预处理的细胞则观察到相反的变化，特别是在浓度为 40μM 时。Aβ 处理抑制了 Nrf2 的表达，依达拉奉可挽救 Nrf2 的核易位。Nrf2 的基因抑制大大降低了依达拉奉对 Aβ 诱导的细胞凋亡和细胞毒性的保护作用，同时 SOD 和 HO-1 的表达也降低。
Nrf2/ARE 信号通路的激活可能是依达拉奉对与阿尔茨海默病相关的氧化损伤的保护作用的基础。
