活性氧
生物
线粒体ROS
星形胶质细胞
细胞生物学
白血病抑制因子
细胞凋亡
氧化应激
线粒体
细胞内
程序性细胞死亡
车站3
下调和上调
内生
信号转导
生物化学
内分泌学
中枢神经系统
胚胎干细胞
基因
作者
Daniel W. Lapp,Samuel S. Zhang,Colin J. Barnstable
出处
期刊:Glia
[Wiley]
日期:2013-12-05
卷期号:62 (2): 159-170
被引量:33
摘要
Reactive oxygen species (ROS) have been implicated in various types of CNS damage, including stroke. We used a cultured astrocyte model to explore mechanisms of survival of CNS cells following ROS damage. We found that pretreatment with leukemia inhibitory factor (LIF) preserves astrocytes exposed to toxic levels of t-BHP by inhibiting an increase in intracellular ROS following t-BHP treatment. Astrocytes lacking functional Stat3 did not benefit from the pro-survival or antioxidant effects of LIF. Inhibition of mitochondrial uncoupling protein 2 (UCP2) using a chemical inhibitor or siRNA abrogates the prosurvival effects of LIF, indicating a critical role for UCP2 in modulation of mitochondrial ROS production in survival following ROS exposure. LIF treatment of astrocytes results in increased UCP2 mRNA that is accompanied by an increase in Stat3 binding to the UCP2 promoter region. Although treatment with LIF alone did not increase UCP2 protein, a combination of LIF treatment and ROS stress led to increased UCP2 protein levels. We conclude that LIF protects astrocytes from ROS-induced death by increasing UCP2 mRNA, allowing cells to respond to ROS stress by rapidly producing UCP2 protein that ultimately decreases endogenous mitochondrial ROS production.
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