Background: Stroke is the leading cause of disability and the third leading cause of death in the world, and no effective treatment has been developed. Oxidative stress-induced cell injury and genomic instability is implicated in the pathogenesis of stroke, whose prognosis remains poor.
Methods: A model of cerebral ischemic/reperfusion injury model was established through four artery occlusions. This study was carried out using western blot, flow cytometry and RT-PCR on cell line U251-MG. The cytotoxic effect of H2O2 and expression of LDH, caspase-3, MDA and SOD was analyzed by assay kit.
Results: We found that the expression of WDR26 was induced in cerebral ischemia-reperfusion injury in vivo and the expression of WDR26 was induced by H2O2 in a dose- and time-dependent manner in vitro. WDR26 over-expression significantly suppressed H2O2-induced cell death and caspase-3-mediated apoptosis in U251-MG cells. In contrast, inhibition of WDR26 markedly enhanced cell death in U251-MG cells. In addition, WDR26 regulated oxidative stress response and induced Nrf2/HO-1 pathway.
Conclusions: These findings suggest that WDR26 mediates H2O2-induced oxidative stress and cell injury, possibly by reducing the intrinsic apoptotic pathway and activating Nrf2 and HO-1 in astrocytes.
Keywords: Astrocyte; HO-1; Nrf2; Oxidative stress; WDR26.
© 2021. The Author(s), under exclusive licence to Springer Nature B.V.