Ying Liu1,2,3, Yao Zhao1,2,3, Kexin Li1,2,3, Shuying Miao4, Yunfei Xu1,2,3, Jie Zhao5,6. 1. Department of Pathophysiology, Xiangya School of Medicine, Central South University, Changsha, 410008, Hunan, China. 2. Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China. 3. Sepsis Translational Medicine Key Lab of Hunan Province, Changsha, 410008, Hunan, China. 4. Department of Pathology, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, 210008, Jiangsu, China. 5. Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China. steelzj@csu.edu.cn. 6. Sepsis Translational Medicine Key Lab of Hunan Province, Changsha, 410008, Hunan, China. steelzj@csu.edu.cn.
Abstract
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.
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.
Authors: Rodica E Petrea; Alexa S Beiser; Sudha Seshadri; Margaret Kelly-Hayes; Carlos S Kase; Philip A Wolf Journal: Stroke Date: 2009-02-10 Impact factor: 7.914