背景:中风是导致残疾的主要原因,也是世界上第三大死亡原因,并没有开发出有效的治疗方法。氧化应激诱导的细胞损伤和基因组不稳定与中风的发病机制有关。其预后仍然较差。
方法:通过4条动脉闭塞建立脑缺血再灌注损伤模型。这项研究是使用蛋白质印迹进行的,U251-MG细胞的流式细胞术和RT-PCR。H2O2的细胞毒作用和LDH的表达,用试剂盒分析caspase-3、MDA和SOD。
结果:我们发现WDR26的表达在体内脑缺血再灌注损伤中被诱导,WDR26的表达在体外呈剂量和时间依赖性。WDR26过表达显著抑制H2O2诱导的U251-MG细胞死亡和caspase-3介导的凋亡。相比之下,抑制WDR26显著增强U251-MG细胞的细胞死亡。此外,WDR26调节氧化应激反应并诱导Nrf2/HO-1通路。
结论:这些发现表明WDR26介导H2O2诱导的氧化应激和细胞损伤,可能通过减少内源性凋亡途径并激活星形胶质细胞中的Nrf2和HO-1。
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.