Nitric oxide activates an Nrf2/sulfiredoxin antioxidant pathway in macrophages
Nitric oxide activates an Nrf2/sulfiredoxin antioxidant pathway in macrophages
复制标题
DOI：
10.1016/j.freeradbiomed.2011.03.039
复制
发表时间：
2011-07-01
影响因子：
7.4
通讯作者：
Drapier, Jean-Claude
中科院分区：
文献类型：
--
作者：
Abbas, Kahina;Breton, Jacques;Drapier, Jean-Claude
过氧化物还原酶（Peroxiredoxins，Prx's）是一类通过催化有机氢过氧化物、H2 O2和过氧亚硝酸盐的还原来维持巯基稳态的过氧化物酶。在氧化应激条件下，真核生物Prx's可通过催化半胱氨酸的底物依赖性氧化为亚磺酸而失活，亚磺酸可调节H2 O2的细胞内信使功能。一个小的氧化还原蛋白，硫氧还蛋白（Srx），仅在真核生物中保守，已被证明可以减少亚磺酰化的2-Cys Prx的，增加了H2 O2信号网络的复杂性。在这项研究中，我们解决了免疫刺激的原代巨噬细胞，产生活性氧（ROS）和一氧化氮（NO中心点）Srx表达的调节。我们目前的遗传证据表明，NO介导的Srx上调是由转录因子核因子红细胞2相关因子（Nrf 2）介导的。我们还表明，NO中心点/Srx途径抑制ROS的产生。这些结果揭示了先天免疫和H2 O2信号之间的联系。我们提出，一个NO（中心点）Nrf 2/Srx通路参与维持氧化还原稳态在精氨酸激活的巨噬细胞和其他炎症设置。(C)2011 Elsevier Inc. All rights reserved.
Peroxiredoxins (Prx's) are a family of peroxidases that maintain thiol homeostasis by catalyzing the reduction of organic hydroperoxides, H2O2, and peroxynitrite. Under conditions of oxidative stress, eukaryotic Prx's can be inactivated by the substrate-dependent oxidation of the catalytic cysteine to sulfinic acid, which may regulate the intracellular messenger function of H2O2. A small redox protein, sulfiredoxin (Srx), conserved only in eukaryotes, has been shown to reduce sulfinylated 2-Cys Prx's, adding to the complexity of the H2O2 signaling network. In this study, we addressed the regulation of Srx expression in immunostimulated primary macrophages that produce both reactive oxygen species (ROS) and nitric oxide (NO center dot). We present genetic evidence that NO-mediated Srx up-regulation is mediated by the transcription factor nuclear factor erythroid 2-related factor (Nrf2). We also show that the NO center dot/Srx pathway inhibits generation of ROS. These results reveal a link between innate immunity and H2O2 signaling. We propose that an NO(center dot)Nrf2/Srx pathway participates in the maintenance of redox homeostasis in cytokine-activated macrophages and other inflammatory settings. (C) 2011 Elsevier Inc. All rights reserved.