Nuclear and cytoplasmic peroxlredoxin-1 differentially regulate NF-κB activities
Nuclear and cytoplasmic peroxlredoxin-1 differentially regulate NF-κB activities
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DOI：
10.1016/j.freeradbiomed.2007.04.029
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发表时间：
2007-07-15
影响因子：
7.4
通讯作者：
Jones, Dean P.
中科院分区：
文献类型：
--
作者：
Hansen, Jason M.;Moriarty-Craige, Siobhan;Jones, Dean P.
过氧化物酶（Peroxiredoxins，Prx）是一种分布广泛、含量丰富的蛋白质，它控制着过氧化物的浓度和相关的信号传导机制。Prx I存在于细胞质和细胞核中，但对氧化还原信号和氧化应激过程中的区室化Prx 1功能知之甚少。我们靶向表达载体以增加HeLa细胞中细胞核（NLS-Prx 1）和细胞质（NES-Prx 1）中的Prx 1。结果显示NES-Prx 1抑制NF-κ B的活化和核转位。相反，增加NLS-Prx 1不影响NF-κ B核转位，但增加NF-κ B报告基因的活性。NLS-Prx 1和NES-Prx 1均抑制NF-κ B p50氧化，表明p50 DNA结合结构域中氧化还原敏感性半胱氨酸的氧化通过两个隔室中的过氧化物代谢来调节。有趣的是，用H2 O2处理后，核硫氧还蛋白-1（Trx 1）的氧化还原状态受到NLS-Prx 1的保护，细胞质Trx 1受到NES-Prx 1的保护。从增加Prx 1的房室差异表明，细胞质和核硫醇系统的氧化还原平衡可以通过过氧化物消除动态控制。这种空间分辨率和蛋白质特异性氧化还原。差异意味着微区室中过氧化物产生/代谢的平衡提供了氧化还原信号传导的重要的特定组分。(C)2007年爱思唯尔公司All rights reserved.
Peroxiredoxins (Prx) are widely distributed and abundant proteins, which control peroxide concentrations and related signaling mechanisms. Prx I is found in the cytoplasm and nucleus, but little is known about compartmentalized Prx1 unction during redox signaling and oxidative stress. We targeted expression vectors to increase Prx1 in nuclei (NLS-Prx1 and cytoplasm (NES-Prx1) in HeLa cells. Results showed that NES-Prx1 inhibited NF-KB activation and nuclear translocation. In contrast, increased NLS-Prx1 did not affect NF-KB nuclear translocation but increased activity of a NF-KB reporter. Both NLS-Prx1 and NES-Prx1 inhibited NF-KB p50 oxidation, suggesting that oxidation of the redox-sensitive cysteine in p50's DNA-binding domain is regulated via peroxide metabolism in both compartments. Interestingly, following treatment with H2O2, nuclear thioredoxin-1 (Trx1) redox status was protected by NLS-Prxl, and cytoplasmic Trx1 was protected by NES-Prx1. Compartmental differences from increasing Prx1 show that the redox poise of cytoplasmic and nuclear thiol systems can be dynamically controlled through peroxide elimination. Such spatial resolution and protein-specific redox. differences imply that the balance of peroxide generation/metabolism in microcompartments provides an important specific component of redox signaling. (C) 2007 Elsevier Inc. All rights reserved.