Hyperoxidation of Peroxiredoxins: Gain or Loss of Function?
Hyperoxidation of Peroxiredoxins: Gain or Loss of Function?
复制标题
DOI：
10.1089/ars.2017.7214
复制
发表时间：
2017-09
影响因子：
6.6
通讯作者：
E. Veal;Zoe E Underwood;L. Tomalin;B. Morgan;C. S. Pillay
中科院分区：
文献类型：
--
作者：
E. Veal;Zoe E Underwood;L. Tomalin;B. Morgan;C. S. Pillay
意义 2003 年，结构研究表明，真核 2-Cys 过氧化还原蛋白 (Prx) 已进化为对其过氧化物反应催化半胱氨酸的过度氧化（亚磺酰化）导致的硫氧还蛋白过氧化物酶活性失活敏感。与此同时，还有一个意想不到的发现，即这种半胱氨酸的亚磺酰化在体内是可逆的，并且鉴定出了一种新酶硫氧还蛋白，该酶显然是共同进化的，专门用于减少过度氧化的 2-Cys Prx，恢复其过氧化物酶活性。总之，这些发现为调查这种可逆 Prx 过度氧化的目的的多项研究提供了动力。最新进展：有人认为，根据具体情况，通过过度氧化抑制硫氧还蛋白过氧化物酶活性既可以促进也可以抑制过氧化物信号转导。 Prx 过度氧化也被提议通过保留还原的硫氧还蛋白和/或通过增加 Prx 的非过氧化物酶分子伴侣或信号活性来保护细胞免受活性氧 (ROS) 诱导的损伤。关键问题在这里，我们将考虑到 Prx 过度氧化发生的体内环境以及硫氧还蛋白的作用，回顾支持这些拟议功能的证据。因此，我们将尝试解释 Prx 过度氧化在氧化还原信号传导中看似矛盾的作用的基础。未来方向 我们基于模型和实验研究提供了一个基本原理，说明为什么 Prx 过度氧化应被视为破坏 ROS 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检测超氧化 Prx 作为昼夜节律的保守特征的影响。抗氧化剂。氧化还原信号。 28、574-590。
SIGNIFICANCE 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. CRITICAL ISSUES 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. FUTURE DIRECTIONS 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.