NADPH oxidase produces reactive oxygen species and maintains survival of rat astrocytes
NADPH oxidase produces reactive oxygen species and maintains survival of rat astrocytes
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DOI：
10.1002/cbf.1171
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发表时间：
2005-03-01
影响因子：
3.6
通讯作者：
Zheng, RL
中科院分区：
文献类型：
--
作者：
Liu, Q;Kang, JH;Zheng, RL
活性氧（reactive oxygen species，ROS）参与了神经退行性疾病的发病机制，而NADPH氧化酶是参与ROS介导的信号转导的重要酶。本研究的目的是确定NADPH氧化酶是否在大鼠星形胶质细胞的ROS生成和细胞存活中发挥作用。我们发现，大鼠星形胶质细胞中ROS的释放显着增加的刺激与钙离子载体或调理酵母聚糖，这是已知的触发呼吸爆发吞噬细胞的NADPH氧化酶途径。进一步的研究表明，NADPH氧化酶抑制剂二苯基碘鎓（DPI）能显著抑制钙离子载体或调理酵母多糖引起的ROS释放增加。细胞存活率测定和吖啶橙子和溴化乙锭荧光双染显示DPI剂量和时间依赖性地降低正常星形胶质细胞的存活率，而外源性补充H2O2可以逆转DPI处理的星形胶质细胞的存活。我们的研究结果首次表明，NADPH氧化酶是星形胶质细胞中产生ROS的重要酶，NADPH氧化酶产生的ROS在星形胶质细胞的存活中起着至关重要的作用。版权所有（C）2004约翰威利父子有限公司。
Reactive oxygen species (ROS) produced by activated astrocytes have been considered to be involved in the pathogenesis of neurodegenerative diseases, while NADPH oxidase is an essential enzyme involved in ROS-mediated signal transduction. The goal of the present study was to determine whether NADPH oxidase plays a role in ROS generation and cell survival in rat astrocytes. We found that the release of ROS in rat astrocytes was significantly increased by stimulation with calcium ionophore or opsonized zymosan, which are known to trigger a respiration burst in phagocytes by the NADPH oxidase pathway. Further study indicated that diphenylene iodonium (DPI), an inhibitor of NADPH oxidase, significantly suppressed the increase of ROS release caused by the calcium ionophore or opsonized zymosan. Cell survival assay and fluorescence double dyeing with acridine orange and ethidium bromide showed that DPI dose- and time-dependently decreased the viability of normal astrocytes, whereas exogenous supplementation of H2O2 can reverse the survival of DPI-treated astrocytes. For the first time, our results suggest that NADPH oxidase is an important enzyme for the generation of ROS in astrocytes, and the ROS generated by NADPH oxidase play an essential role in astrocyte survival. Copyright (C) 2004 John Wiley Sons, Ltd.