1 Institute for Cell and Molecular Biosciences, Newcastle University , Newcastle upon Tyne, United Kingdom .
2 Newcastle University Institute for Ageing, Newcastle University , Newcastle upon Tyne, United Kingdom .
Antioxid Redox Signal. 2018 Mar 1;28(7):574-590. doi: 10.1089/ars.2017.7214. Epub 2017 Sep 8.
In 2003, structural studies revealed that eukaryotic 2-Cys peroxiredoxins (Prx) have evolved to be sensitive to inactivation of their thioredoxin peroxidase activity by hyperoxidation (sulfinylation) of their peroxide-reacting catalytic cysteine. This was accompanied by the unexpected discovery, that the sulfinylation of this cysteine was reversible in vivo and the identification of a new enzyme, sulfiredoxin, that had apparently co-evolved specifically to reduce hyperoxidized 2-Cys Prx, restoring their peroxidase activity. Together, these findings have provided the impetus for multiple studies investigating the purpose of this reversible, Prx hyperoxidation. Recent Advances: It has been suggested that inhibition of the thioredoxin peroxidase activity by hyperoxidation can both promote and inhibit peroxide signal transduction, depending on the context. Prx hyperoxidation has also been proposed to protect cells against reactive oxygen species (ROS)-induced damage, by preserving reduced thioredoxin and/or by increasing non-peroxidase chaperone or signaling activities of Prx.
Here, we will review the evidence in support of each of these proposed functions, in view of the in vivo contexts in which Prx hyperoxidation occurs, and the role of sulfiredoxin. Thus, we will attempt to explain the basis for seemingly contradictory roles for Prx hyperoxidation in redox signaling.
We provide a rationale, based on modeling and experimental studies, for why Prx hyperoxidation should be considered a suitable, early biomarker for damaging levels of ROS. We discuss the implications that this has for the role of Prx in aging and the detection of hyperoxidized Prx as a conserved feature of circadian rhythms. Antioxid. Redox Signal. 28, 574-590.
2003 年，结构研究表明，真核生物 2-Cys 过氧化物酶（Prx）进化为对其过氧化物反应催化半胱氨酸的过氧化物（亚磺酰化）失活敏感。伴随着这一发现，出乎意料的是，体内半胱氨酸的亚磺酰化是可逆的，并且鉴定出一种新的酶，硫氧还蛋白还原酶，显然是共同进化的，专门用于还原过氧化物化的 2-Cys Prx，恢复其过氧化物酶活性。这些发现共同为研究这种可逆的 Prx 过氧化物化的目的提供了动力。
有人认为，过氧化物化对半胱氨酸的硫氧还蛋白过氧化物酶活性的抑制可以根据具体情况促进和抑制过氧化物信号转导。还提出过氧化物化可以通过保护还原型硫氧还蛋白和/或增加非过氧化物伴侣或 Prx 的信号转导活性来保护细胞免受活性氧（ROS）诱导的损伤。
在这里，我们将根据过氧化物化发生的体内环境以及硫氧还蛋白还原酶的作用，回顾支持这些功能的证据。因此，我们将试图解释 Prx 过氧化物化在氧化还原信号中的看似矛盾的作用的基础。
我们基于建模和实验研究提供了一个理由，说明为什么 Prx 过氧化物化应该被认为是 ROS 损伤水平的合适的早期生物标志物。我们讨论了这对 Prx 在衰老中的作用以及将过氧化物化的 Prx 作为昼夜节律的保守特征检测的影响。抗氧化剂。氧化还原信号。28,574-590。
