Institute of Biochemistry and Molecular Biology I, Heinrich Heine University, Düsseldorf, University, D-40225, Düsseldorf, Germany; email:
Leibniz Research Institute for Environmental Medicine, Heinrich Heine University, D-40225, Düsseldorf, Germany.
Annu Rev Biochem. 2017 Jun 20;86:715-748. doi: 10.1146/annurev-biochem-061516-045037. Epub 2017 Apr 24.
Oxidative stress is two sided: Whereas excessive oxidant challenge causes damage to biomolecules, maintenance of a physiological level of oxidant challenge, termed oxidative eustress, is essential for governing life processes through redox signaling. Recent interest has focused on the intricate ways by which redox signaling integrates these converse properties. Redox balance is maintained by prevention, interception, and repair, and concomitantly the regulatory potential of molecular thiol-driven master switches such as Nrf2/Keap1 or NF-κB/IκB is used for system-wide oxidative stress response. Nonradical species such as hydrogen peroxide (HO) or singlet molecular oxygen, rather than free-radical species, perform major second messenger functions. Chemokine-controlled NADPH oxidases and metabolically controlled mitochondrial sources of HO as well as glutathione- and thioredoxin-related pathways, with powerful enzymatic back-up systems, are responsible for fine-tuning physiological redox signaling. This makes for a rich research field spanning from biochemistry and cell biology into nutritional sciences, environmental medicine, and molecular knowledge-based redox medicine.
一方面,过多的氧化剂会对生物分子造成损伤;另一方面,维持一定水平的氧化剂挑战,即所谓的氧化适度应激,对于通过氧化还原信号来控制生命过程是至关重要的。最近,人们的兴趣集中在氧化还原信号整合这些相反性质的复杂方式上。氧化还原平衡通过预防、拦截和修复来维持,同时,分子硫醇驱动的主开关(如 Nrf2/Keap1 或 NF-κB/IκB)的调节潜力被用于全系统的氧化应激反应。非自由基物质(如过氧化氢 (HO) 或单线态氧)而不是自由基物质,发挥主要的第二信使功能。趋化因子控制的 NADPH 氧化酶和代谢控制的线粒体 HO 来源,以及与谷胱甘肽和硫氧还蛋白相关的途径,具有强大的酶备份系统,负责微调生理氧化还原信号。这使得研究领域涵盖了从生物化学和细胞生物学到营养科学、环境医学和基于分子知识的氧化还原医学等多个领域。