Edaravone reduces Aβ-induced oxidative damage in SH-SY5Y cells by activating the Nrf2/ARE signaling pathway

• DOI: 10.1016/j.lfs.2019.02.025
• Publication Date: 2019-02-13T03:49:51Z
• Authors: Lei Zhang; Yingying Guo; Heying Wang; Lili Zhao; Zhulin Ma; Tao Li; Jiao Liu; Man Sun; Yating Jian; Li Yao; Yun Du; Guilian Zhang
• Keywords: Amyloid beta-Peptides; Cell Survival; NF-E2-Related Factor 2; Apoptosis; Antioxidant Response Elements; Peptide Fragments; 3. Good health; Disease Models, Animal; Neuroblastoma; Oxidative Stress; 03 medical and health sciences; Neuroprotective Agents; Superoxide Dismutase-1; 0302 clinical medicine; Alzheimer Disease; Cell Line, Tumor; Edaravone; Animals; Humans; Cognitive Dysfunction; Reactive Oxygen Species; Oxidation-Reduction; Signal Transduction

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 Aβ25-35. 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 Aβ25-35-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. Aβ25-35-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 Aβ25-35, 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.