NrdH Redoxin Enhances Resistance to Multiple Oxidative Stresses by Acting as a Peroxidase Cofactor in Corynebacterium glutamicum
NrdH Redoxin Enhances Resistance to Multiple Oxidative Stresses by Acting as a Peroxidase Cofactor in Corynebacterium glutamicum
复制标题
NrdH 氧化还原蛋白通过充当谷氨酸棒杆菌中的过氧化物酶辅因子来增强对多种氧化应激的抵抗力
DOI：
10.1128/aem.03654-13
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发表时间：
2014-03-01
影响因子：
4.4
通讯作者：
Liu, Shuang-Jiang
中科院分区：
文献类型：
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作者：
Si, Mei-Ru;Zhang, Lei;Liu, Shuang-Jiang
NrdH 氧化还原酶是小蛋白二硫化物氧化还原酶，其行为类似于硫氧还蛋白，但与谷氧还蛋白具有高度的氨基酸序列相似性。尽管 NrdH 氧化还原蛋白被认为是抗氧化系统中的另一个候选者，但它们在氧化应激中的生理作用仍不清楚。在这项研究中，我们证实谷氨酸棒杆菌 NrdH 氧化还蛋白通过专门接收来自硫氧还蛋白还原酶的电子，催化还原 Ib 类核糖核苷酸还原酶 (RNR)、胰岛素和 5,5'-二硫双-(2-硝基苯甲酸) (DTNB) 中的二硫键。 NrdH 的过度表达通过减少 ROS 积累来增加谷氨酸棒杆菌对多种氧化应激的抵抗力。因此，当谷氨酸棒杆菌野生型菌株暴露于氧化应激条件时，观察到nrdH基因的表达升高。研究发现，NrdH 介导的氧化应激抗性在很大程度上取决于硫醇过氧化物酶 Prx 的存在，因为 NrdH 过表达介导的氧化应激抗性增强在 prx 突变体中很大程度上被消除。此外，我们发现 NrdH 通过直接靶向并作为 Prx 的电子供体来促进 Prx 的氢过氧化物还原活性。因此，我们提供的证据表明，NrdH 氧化还原蛋白可以作为过氧化物酶辅助因子，防止各种外源氧化应激诱导的活性氧 (ROS) 的破坏作用。
NrdH redoxins are small protein disulfide oxidoreductases behaving like thioredoxins but sharing a high amino acid sequence similarity to glutaredoxins. Although NrdH redoxins are supposed to be another candidate in the antioxidant system, their physiological roles in oxidative stress remain unclear. In this study, we confirmed that the Corynebacterium glutamicum NrdH redoxin catalytically reduces the disulfides in the class Ib ribonucleotide reductases (RNR), insulin and 5,5'-dithiobis-(2-nitrobenzoic acid) (DTNB), by exclusively receiving electrons from thioredoxin reductase. Overexpression of NrdH increased the resistance of C. glutamicum to multiple oxidative stresses by reducing ROS accumulation. Accordingly, elevated expression of the nrdH gene was observed when the C. glutamicum wild-type strain was exposed to oxidative stress conditions. It was discovered that the NrdH-mediated resistance to oxidative stresses was largely dependent on the presence of the thiol peroxidase Prx, as the increased resistance to oxidative stresses mediated by overexpression of NrdH was largely abrogated in the prx mutant. Furthermore, we showed that NrdH facilitated the hydroperoxide reduction activity of Prx by directly targeting and serving as its electron donor. Thus, we present evidence that the NrdH redoxin can protect against the damaging effects of reactive oxygen species (ROS) induced by various exogenous oxidative stresses by acting as a peroxidase cofactor.