The amitochondriate eukaryote Trichomonas vaginalis contains a divergent thioredoxin-linked peroxiredoxin antioxidant system
The amitochondriate eukaryote Trichomonas vaginalis contains a divergent thioredoxin-linked peroxiredoxin antioxidant system
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DOI：
10.1074/jbc.m304359200
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发表时间：
2004-02-13
影响因子：
4.8
通讯作者：
Müller, S
中科院分区：
文献类型：
--
作者：
Coombs, GH;Westrop, GD;Müller, S
毛滴虫是一种无线粒体寄生原生动物专门为厌氧生活方式。然而，它暴露在氧气中，能够科普由此产生的氧化应激。在没有谷胱甘肽的情况下，半胱氨酸被认为是主要的抗氧化剂。我们现在报告说，寄生虫含有硫氧还蛋白还原酶，其功能与硫氧还蛋白和硫氧还蛋白过氧化物酶一起解毒潜在的破坏性氧化剂。硫氧还蛋白还原酶和硫氧还蛋白还还原胱氨酸，因此可能在维持细胞半胱氨酸水平中起作用。硫氧还蛋白系统作为毛滴虫的主要抗氧化防御机制之一的重要性通过显示寄生虫通过上调硫氧还蛋白和硫氧还蛋白过氧化物酶水平对导致氧化应激增加的环境变化作出反应而得到证实。序列数据表明，毛癣菌的硫氧还蛋白还原酶在结构上与其人类宿主的硫氧还蛋白还原酶有根本不同，因此可能是一个有用的药物靶点。该蛋白质通常类似于存在于其他低等真核生物中的硫氧还蛋白还原酶，所有这些都可能起源于原核生物的水平基因转移。硫氧还蛋白过氧化物酶的系统发育信号很弱，但来自树木的证据表明，该基因已受到重复的水平基因转移从不同的原核生物到不同的真核生物。因此，这些数据是一致的复杂性假设，预测简单的途径，如硫氧还蛋白级联的演变可能会受到物种之间的水平基因转移。
Trichomonas is an amitochondriate parasitic protozoon specialized for an anaerobic lifestyle. Nevertheless, it is exposed to oxygen and is able to cope with the resultant oxidative stress. In the absence of glutathione, cysteine has been thought to be the major antioxidant. We now report that the parasite contains thioredoxin reductase, which functions together with thioredoxin and thioredoxin peroxidase to detoxify potentially damaging oxidants. Thioredoxin reductase and thioredoxin also reduce cystine and so may play a role in maintaining the cellular cysteine levels. The importance of the thioredoxin system as one of the major antioxidant defense mechanisms in Trichomonas was confirmed by showing that the parasite responds to environmental changes resulting in increased oxidative stress by upregulating thioredoxin and thioredoxin peroxidases levels. Sequence data indicate that the thioredoxin reductase of Trichomonas differs fundamentally in structure from that of its human host and thus may represent a useful drug target. The protein is generally similar to thioredoxin reductases present in other lower eukaryotes, all of which probably originated through horizontal gene transfer from a prokaryote. The phylogenetic signal in thioredoxin peroxidase is weak, but evidence from trees suggests that this gene has been subject to repeated horizontal gene transfers from different prokaryotes to different eukaryotes. The data are thus consistent with the complexity hypothesis that predicts that the evolution of simple pathways such as the thioredoxin cascade are likely to be affected by horizontal gene transfer between species.