氧化还原对 NLRP3 介导的炎症和脓毒症的调控。

Q3 Biochemistry, Genetics and Molecular Biology
N Yu Rusetskaya, N Yu Loginova, E P Pokrovskaya, Yu S Chesovskikh, L E Titova
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引用次数: 0

摘要

这篇综述探讨了有关 NLRP3 炎症体和气体蛋白的激活和氧化还原调节机制的现代数据,以及硒在这些过程中的作用。炎症小体的激活和化脓是一种进化过程中保留下来的抵御病原体的机制,在各种类型的细胞和组织(巨噬细胞和单核细胞、小胶质细胞和星形胶质细胞、荚膜细胞和肾脏实质细胞、牙周组织、破骨细胞和成骨细胞以及消化系统和泌尿系统细胞等)中都有描述。根据氧化还原调节的特点,NLRP3 炎症和热解的参与者可细分为两类。第一类成员阻断线粒体电子传递链,促进活性氧的形成和氧化应激的发展。这一类包括颗粒酶、线粒体抗病毒信号蛋白 MAVS 等。第二类包括硫氧还蛋白相互作用蛋白(TXNIP)、红细胞衍生核因子-2(NRF2)、Kelch 样 ECH 相关蛋白 1(Keap1)、ninjurin(Ninj1)、scramblase(TMEM16)、炎性体调控蛋白激酶 NLRP3(NEK7)、caspase-1、gasdermins GSDM B、D 等。它们具有氧化还原敏感域和/或受氧化还原调节、谷胱甘肽化/去谷胱甘肽化或其他类型调节的半胱氨酸残基。抑制氧化应激和对 NLRP3 炎症和化脓过程参与者的氧化还原调节取决于抗氧化酶谷胱甘肽过氧化物酶(GPX)和硫氧还原酶(TRXR)的活性,这两种酶的活性位点含有硒半胱氨酸残基 Sec。GPX 和 TRXR 的表达受 NRF2 调节,并取决于血液中的硒浓度。缺硒会导致 Sec UGA 密码子翻译无效、翻译终止,进而合成无活性的硒蛋白,从而引起各种类型的程序性细胞死亡:神经细胞和精子凋亡、红细胞前体坏死、受感染的髓细胞热凋亡、T 淋巴细胞和 B 淋巴细胞、肾脏和胰腺细胞铁凋亡。此外,与最佳硒浓度(1.43 μM或113 μg/l)相比,血液中的次优硒浓度(0.86 μM或68 μg/l或更低)对250多个基因的表达有显著影响。综上所述,我们建议将血硒浓度视为细胞氧化还原平衡的一个重要参数。血硒浓度不达标(或缺硒状态)应被用于评估发生炎症过程的风险。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Redox regulation of the NLRP3-mediated inflammation and pyroptosis.

The review considers modern data on the mechanisms of activation and redox regulation of the NLRP3 inflammasome and gasdermins, as well as the role of selenium in these processes. Activation of the inflammasome and pyroptosis represent an evolutionarily conserved mechanism of the defense against pathogens, described for various types of cells and tissues (macrophages and monocytes, microglial cells and astrocytes, podocytes and parenchymal cells of the kidneys, periodontal tissues, osteoclasts and osteoblasts, as well as cells of the digestive and urogenital systems, etc.). Depending on the characteristics of redox regulation, the participants of NLRP3 inflammation and pyroptosis can be subdivided into 2 groups. Members of the first group block the mitochondrial electron transport chain, promote the formation of reactive oxygen species and the development of oxidative stress. This group includes granzymes, the mitochondrial antiviral signaling protein MAVS, and others. The second group includes thioredoxin interacting protein (TXNIP), erythroid-derived nuclear factor-2 (NRF2), Kelch-like ECH-associated protein 1 (Keap1), ninjurin (Ninj1), scramblase (TMEM16), inflammasome regulatory protein kinase NLRP3 (NEK7), caspase-1, gasdermins GSDM B, D and others. They have redox-sensitive domains and/or cysteine residues subjected to redox regulation, glutathionylation/deglutathionylation or other types of regulation. Suppression of oxidative stress and redox regulation of participants in NLRP3 inflammation and pyroptosis depends on the activity of the antioxidant enzymes glutathione peroxidase (GPX) and thioredoxin reductase (TRXR), containing a selenocysteine residue Sec in the active site. The expression of GPX and TRXR is regulated by NRF2 and depends on the concentration of selenium in the blood. Selenium deficiency causes ineffective translation of the Sec UGA codon, translation termination, and, consequently, synthesis of inactive selenoproteins, which can cause various types of programmed cell death: apoptosis of nerve cells and sperm, necroptosis of erythrocyte precursors, pyroptosis of infected myeloid cells, ferroptosis of T- and B-lymphocytes, kidney and pancreatic cells. In addition, suboptimal selenium concentrations in the blood (0.86 μM or 68 μg/l or less) have a significant impact on expression of more than two hundred and fifty genes as compared to the optimal selenium concentration (1.43 μM or 113 μg/l). Based on the above, we propose to consider blood selenium concentrations as an important parameter of redox homeostasis in the cell. Suboptimal blood selenium concentrations (or selenium deficiency states) should be used for assessment of the risk of developing inflammatory processes.

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来源期刊
Biomeditsinskaya khimiya
Biomeditsinskaya khimiya Biochemistry, Genetics and Molecular Biology-Biochemistry, Genetics and Molecular Biology (all)
CiteScore
1.30
自引率
0.00%
发文量
49
期刊介绍: The aim of the Russian-language journal "Biomeditsinskaya Khimiya" (Biomedical Chemistry) is to introduce the latest results obtained by scientists from Russia and other Republics of the Former Soviet Union. The Journal will cover all major areas of Biomedical chemistry, including neurochemistry, clinical chemistry, molecular biology of pathological processes, gene therapy, development of new drugs and their biochemical pharmacology, introduction and advertisement of new (biochemical) methods into experimental and clinical medicine etc. The Journal also publish review articles. All issues of journal usually contain invited reviews. Papers written in Russian contain abstract (in English).
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