Genetic mapping of six mouse peroxiredoxin genes and fourteen peroxiredoxin related sequences.
Genetic mapping of six mouse peroxiredoxin genes and fourteen peroxiredoxin related sequences.
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六个小鼠过氧化还原蛋白基因和十四个过氧化还原蛋白相关序列的遗传图谱。
DOI：
10.1007/s003359901150
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发表时间：
1999
期刊：
影响因子：
--
通讯作者：
Kozak,CA
中科院分区：
文献类型：
--
作者：
Lyu,MS;Rhee,SG;Chae,HZ;Lee,TH;Adamson,MC;Kang,SW;Jin,DY;Jeang,KT;Kozak,CA
生活在有氧环境中的生物需要防止或限制由呼吸过程中氧气不完全还原引起的活性氧物种(O2、−、H2O2和HO)造成的细胞损伤的机制。或者，损伤可由暴露于外部因素，如光、辐射、氧化还原循环药物或刺激宿主吞噬细胞造成(Sies 1993；Halliwell和Gutteridge，1989)。活性氧会对所有主要的生物大分子造成损害，导致蛋白质氧化、脂质过氧化、DNA碱基修饰和链断裂。为了防止这些破坏性的过程，生物体已经开发出一系列抗氧化防御系统(Halliwell和Gutteridge 1989；Amstad等人)。1991年)。预防性抗氧化剂系统包括分解过氧化物和超氧阴离子的酶，以及隔离金属离子的化合物。这些类型的抗氧化剂可以减少或消除自由基的产生。断链抗氧化剂，如抗坏血酸和α-生育酚，清除瞬时自由基，并抑制这些活性物种对生物靶标的攻击。我们先前已经从酵母中纯化了一种25 kDa的酶，它可以防止硫醇氧化系统而不是抗坏血酸氧化系统引起的损伤，尽管这两个系统的氧化应激程度相似，根据诱导的谷氨酰胺合成酶失活的程度来判断(Kim等人)。(1988年)。因此，我们最初将这种蛋白质命名为硫代特异性抗氧化剂(TSA)。虽然当时还不知道TSA消除氧化剂的确切性质，但TSA作为抗氧化剂的重要性是显而易见的，因为对酵母施加氧化压力导致TSA合成增加，并且TSA蛋白占好氧培养酵母总可溶性蛋白的0.7%(Kim等人)。(1989年)。对酵母TSA基因进行了克隆和测序(Chae等人)。1993年)。它与任何已知的过氧化氢酶、超氧化物歧化酶或过氧化物酶没有明显的同源性。这种同源性的缺乏与观察到的TSA不具有传统抗氧化酶的催化活性特征一致。通过同源重组构建了一个不能产生TSA的酵母突变株(Chae等人)。1993年)。突变株和野生型菌株在厌氧条件下的生长速度相同。然而，在好氧条件下，特别是在氧化应激下，突变酵母的生长速度明显低于野生型酵母。数据库搜索显示，来自各种生物的一些蛋白质与TSA相似(Chae等人)。1994年b)。这些同源蛋白现在被命名为过氧化还蛋白(PRDX)家族。我们最近证明，TSA的抗氧化活性归因于其还原过氧化氢的能力。抗氧化功能对硫醇的明显特殊要求是因为被氧化的TSA的分子间二硫键可以被硫醇还原，但不能被抗坏血酸还原。我们已经证明硫氧还蛋白(TRX)是TSA还原的生理性电子供体(Chae等人)。1994a)。因此，TSA是第一个被鉴定为TRX为直接电子供体的过氧化物酶，因此被重新命名为TRX过氧化物酶(TPX)。尽管有这一发现，TSA同源物(PRDX基因家族)并不被称为TPX家族，因为并不是所有的成员都使用TRX作为氢供体。例如，肠道细菌同源物AhpC和锥虫同源物C22分别从AhpF和C30蛋白获得电子，用于还原过氧化氢(Jacobson等人。1989年--…
Organisms living in aerobic environments require mechanisms that prevent or limit cellular damage caused by reactive oxygen species (O2−, H2O2, and HO) that arise from the incomplete reduction of oxygen during respiration. Alternatively, damage can result from exposure to external agents such as light, radiation, redox-cycling drugs, or stimulated host phagocytes (Sies 1993; Halliwell and Gutteridge, 1989). The reactive oxygen species cause damage to all major classes of biological macromolecules leading to protein oxidation, lipid peroxidation, and DNA base modifications and strand breaks. To guard against these destructive processes, organisms have developed a battery of antioxidant defenses (Halliwell and Gutteridge 1989; Amstad et al. 1991). The preventive antioxidant systems include enzymes that decompose peroxides and superoxide anion and compounds that sequester metal ions. These types of antioxidants reduce or eliminate the generation of free radicals. Chain-breaking antioxidants, such as ascorbate and α-tocopherol, scavenge transient free radicals and inhibit the attack of these reactive species on biological targets. We have previously purified a 25-kDa enzyme from yeast that prevents damage induced by the thiol oxidation system but not by the ascorbate oxidation system, despite the fact that the degree of oxidative stress is similar for the two systems as judged by the comparable extent of induced inactivation of glutamine synthetase (Kim et al. 1988). Thus, we originally named this protein thiolspecific antioxidant (TSA). Although the exact nature of the oxidant eliminated by TSA was not known at that time, the importance of TSA as an antioxidant was readily apparent as the application of oxidative pressure to yeast resulted in an increase in the synthesis of TSA, and TSA protein constituted 0.7% of total soluble protein from yeast grown aerobically (Kim et al. 1989). Yeast TSA gene was cloned and sequenced (Chae et al. 1993). It shows no significant homology to any known catalase, superoxide dismutase, or peroxidase enzymes. This lack of homology is consistent with the observation that TSA does not possess catalytic activity characteristic of conventional antioxidant enzymes. A yeast mutant that cannot produce TSA was constructed by homologous recombination (Chae et al. 1993). The mutant and wild-type strains grew at equal rates under anaerobic conditions. However, under aerobic conditions, especially under oxidative stress, the growth rate of mutant yeast was significantly lower than that of wild-type yeast.A database search revealed a number of proteins from a variety organisms that show similarity to TSA (Chae et al. 1994b). These homologous proteins have now been named the peroxiredoxin (PRDX) family. We recently demonstrated that the antioxidant activity of TSA is attributable to its ability to reduce H2O2. The apparent specific requirement for a thiol for antioxidant function was due to the fact that an intermolecular disulfide linkage of oxidized TSA can be reduced by a thiol but not by ascorbate. We have shown that thioredoxin (TRX) is the physiological electron donor for the reduction of TSA (Chae et al. 1994a). TSA was thus the first peroxidase to be identified for which TRX is the immediate electron donor, and it was therefore renamed TRX peroxidase (TPX). Despite this finding, the TSA homologs (the PRDX gene family) were not termed the TPX family because not all members use TRX as the hydrogen donor. For example, enteric bacteria homolog AhpC and trypanosomatid homolog C22 receive electron from AhpF and C30 proteins, respectively, for the reduction of H2O2 (Jacobson et al. 1989 …