Oxidative stress induces PKR-dependent apoptosis via IFN-γ activation signaling in Jurkat T cells
Oxidative stress induces PKR-dependent apoptosis via IFN-γ activation signaling in Jurkat T cells
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DOI：
10.1016/j.bbrc.2008.10.103
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发表时间：
2008-12-19
影响因子：
3.1
通讯作者：
Choi, Sang-Yun
中科院分区：
文献类型：
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作者：
Pyo, Chul-Woong;Lee, Shin-Hee;Choi, Sang-Yun
dsrna依赖性蛋白激酶PKR是抗病毒防御的核心成分。PKR在多种应激诱导的细胞凋亡中的关键作用进一步证明了它的生物学重要性。在这里，我们分析了氧化应激在诱导Jurkat细胞中pkr依赖性凋亡中的意义。我们的研究结果表明，活性氧（ROS）通过激活干扰素(IFN) γ基因，在转录水平诱导内源性pkr基因的表达。然而，ifn - γ siRNA的表达消除了h2o2介导的pkr诱导。自由基清除剂n -乙酰- l-半胱氨酸通过降低ifn - γ的表达，深刻地抑制pkr的诱导。用特异性JAK-STAT抑制剂AG490处理细胞，可降低PKR表达，抑制PKR依赖性细胞死亡。最后，sirna介导的ifn - γ或pkr缺失有效下调h2o2介导的凋亡细胞死亡。这些结果表明，氧化应激主要通过ifn - γ激活信号诱导PKR表达，并导致Jurkat T细胞凋亡。(C) 2008爱思唯尔公司版权所有。
The dsRNA-dependent protein kinase, PKR, is a central component in antiviral defense. The biological importance of PKR is further remarked by its critical role in apoptosis induced by a variety of stresses. Here, we analyzed the implication of oxidative stress in the induction of PKR-dependent apoptosis in Jurkat cells. Our results revealed that reactive oxygen species (ROS) induced endogenous pkr gene expression at the transcriptional level by activating the interferon (IFN)-gamma gene. However, IFN-gamma siRNA expression abrogated the H2O2-mediated pkr induction. The radical scavenger N-acetyl-L-cysteine profoundly inhibited pkr induction via the reduction of IFN-gamma expression. The treatment of cells with the specific JAK-STAT inhibitor, AG490, reduced the PKR expression, and Suppressed PKR-dependent cell death. Finally, siRNA-mediated depletion of IFN-gamma or pkr efficiently downregulated H2O2-mediated apoptotic cell death. These results indicated that oxidative stress induces PKR expression essentially via the IFN-gamma activation signal, and causes apoptosis in Jurkat T cells. (C) 2008 Elsevier Inc. All rights reserved.