Entamoeba thiol-based redox metabolism: A potential target for drug development
Entamoeba thiol-based redox metabolism: A potential target for drug development
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DOI：
10.1016/j.molbiopara.2016.01.004
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发表时间：
2016-03-01
影响因子：
1.5
通讯作者：
Nozaki, Tomoyoshi
中科院分区：
文献类型：
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作者：
Jeelani, Ghulam;Nozaki, Tomoyoshi
阿米巴病是由人类病原体溶组织内阿米巴引起的一种广泛存在于世界各地的肠道感染。几十年来，甲硝唑一直是治疗阿米巴病的首选药物，尽管它对无症状的包囊携带者效果不佳，而且在其他具有类似厌氧代谢的原生动物中出现了抗药性。因此，迫切需要识别和表征特定的靶点，以设计新的治疗方法来改进阿米巴病的治疗。为了实现这一目标，硫醇依赖的氧化还原代谢尤其令人感兴趣。溶组织埃希菌依赖硫醇的氧化还原代谢包括过氧化还蛋白、红藻蛋白、铁超氧化物歧化酶、黄素氧化还原酶、NADPH：黄素氧化还原酶等蛋白质，以及L半胱氨酸、S甲基L半胱氨酸和硫代脯氨酸(噻唑烷-4-羧酸)等氨基酸。溶组乳杆菌完全缺乏谷胱甘肽及其代谢，L-半胱氨酸是胞内主要的低分子硫醇。此外，该寄生虫还具有一个由硫氧还蛋白和硫氧还蛋白还原酶组成的功能硫氧还蛋白系统，这是一个普遍存在的具有抗氧化和氧化还原调节作用的氧化还原酶系统。本文综述了溶组织埃希氏菌基于硫醇的氧化还原代谢及其调控机制，特别是溶组织埃希氏菌特有的氧化还原代谢系统的特点及其在抗阿米巴病药物开发中的应用。(C)2016年提交人。爱思唯尔出版公司(Elsevier B.V.)
Amebiasis is an intestinal infection widespread throughout the world caused by the human pathogen Entamoeba histolytica. Metronidazole has been a drug of choice against amebiasis for decades despite its low efficacy against asymptomatic cyst carriers and emergence of resistance in other protozoa with similar anaerobic metabolism. Therefore, identification and characterization of specific targets is urgently needed to design new therapeutics for improved treatment against amebiasis. Toward this goal, thiol-dependent redox metabolism is of particular interest. The thiol-dependent redox metabolism in E. histolytica consists of proteins including peroxiredoxin, rubrerythrin, Fe-superoxide dismutase, flavodi-iron proteins, NADPH: flavin oxidoreductase, and amino acids including L-cysteine, S-methyl-L-cysteine, and thioprolines (thiazolidine-4-carboxylic acids). E. histolytica completely lacks glutathione and its metabolism, and L-cysteine is the major intracellular low molecular mass thiol. Moreover, this parasite possesses a functional thioredoxin system consisting of thioredoxin and thioredoxin reductase, which is a ubiquitous oxidoreductase system with antioxidant and redox regulatory roles. In this review, we summarize and highlight the thiol-based redox metabolism and its control mechanisms in E. histolytica, in particular, the features of the system unique to E. histolytica, and its potential use for drug development against amebiasis. (C) 2016 The Authors. Published by Elsevier B.V.