[细菌感染中的宿主防御和氧化应激信号
]。

Takaaki Akaike
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引用次数: 9

摘要

感染过程中产生的一氧化氮(NO)和活性氧(ROS)在宿主防御机制中起着关键作用。生理调节活性氧(ROS)如超氧化物(superoxide)和一氧化氮(NO)是非常重要的。这些活性物质的过量产生可能引起生物分子的氧化损伤。NO和ROS的重要细胞保护和抗菌功能是通过诱导血红素加氧酶(HO)-1介导的。然而,这种HO-1诱导的信号机制尚不清楚。我们在2007年发现了一个独特的第二信使,8-硝基鸟苷3',5'-环单磷酸(8-硝基- cgmp),它在氧化应激和其他细胞氧化还原信号传导过程中介导亲电信号转导。8-硝基cgmp是通过鸟嘌呤与NO和ROS的硝化作用形成的,事实上,在沙门氏菌感染小鼠中发现了NO依赖性的8-硝基cgmp形成和HO-1诱导。HO-1的诱导仅受细胞内形成的8-硝基- cgmp的调控,更重要的是,在这种沙门氏菌感染中,其强大的抗凋亡功能是显而易见的。8-硝基- cgmp具有强大的细胞保护功能,其信号传导似乎通过蛋白质巯基介导,产生翻译后修饰,称为蛋白质s -胍基化。8-硝基- cgmp特异性地s -鸟苷酸Keap1,转录因子Nrf2的负调节因子,反过来上调HO-1的转录。我们最近的研究表明,自噬可能参与了8-硝基cgmp依赖的抗菌作用。8-硝基- cgmp信号也被发现受到具有优越抗氧化活性和独特信号功能的活性硫物质的调控。这篇综述将讨论一种新的宿主防御模式,它通过在微生物感染过程中形成一种独特的细胞信号分子,8-硝基- cgmp。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
[Host defense and oxidative stress signaling in bacterial infection
].

Nitric oxide (NO) and reactive oxygen species (ROS) produced during infection are involved critically in host defense mechanisms. It is quite important to physiologically regulate ROS, such as superoxide, and NO. These reactive species produced in excess may cause oxidative damage of biological molecules. An important cytoprotective and antimicrobial function of NO and ROS is mediated by induction of heme oxygenase (HO)-1. The signaling mechanism of this HO-1 induction has remained unclear, however. We discovered in 2007 a unique second messenger, 8-nitroguanosine 3',5'-cyclic monophosphate (8-nitro-cGMP), that mediates electrophilic signal transduction during oxidative stress and other cellular redox signaling in general. 8-Nitro-cGMP is formed via guanine nitration with NO and ROS, and in fact, NO-dependent 8-nitro-cGMP formation and HO-1 induction were identified in Salmonella-infected mice. HO-1 induction was regulated solely by 8-nitro-cGMP formed in cells, and more important, its potent anti-apoptotic function was evident in such a Salmonella infection. 8-Nitro-cGMP has a potent cytoprotective function, of which signaling appears to be mediated via protein sulfhydryls to generate a post-translational modification called protein S-guanylation. 8-Nitro-cGMP specifically S-guanylates Keap1, a negative regulator of transcription factor Nrf2, which in turn up-regulates transcription of HO-1. Our recent study revealed that the autophagy might be involved in the 8-nitro-cGMP-dependent antimicrobial effect. The 8-nitro-cGMP signaling was also found to be regulated by reactive sulfur species that have superior antioxidant activity and unique signaling function. This review will discuss a new paradigm of the host defense that operates via formation of a unique cell signaling molecule, 8-nitro-cGMP, during microbial infections.

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