Deponte Marcel, Rahlfs Stefan, Becker Katja
Interdisciplinary Research Center, Justus Liebig University, D-35392 Giessen, Germany.
Subcell Biochem. 2007;44:219-29. doi: 10.1007/978-1-4020-6051-9_10.
Cellular redox metabolism is considered to be involved in the pathophysiology of diseases caused by protozoal parasites such as Toxoplasma, Trypanosoma, Leishmania, and Plasmodia. Redox reactions furthermore are thought to play a major role in the action of and the resistance to some clinically used antiparasitic drugs. Interestingly, in malarial parasites, the antioxidant enzymes catalase and glutathione peroxidase are absent which indicates a crucial role of the thioredoxin system in redox control. Besides a glutathione peroxidase-like thioredoxin peroxidase and a glutathione S-transferase with slight peroxidase activity, Plasmodium falciparum (the causative agent of tropical malaria) possesses four classical peroxiredoxins: Two peroxiredoxins of the typical 2-Cys Prx class, one 1-Cys peroxiredoxin with homology to the atypical 2-Cys Prx class, and a peroxiredoxin of the 1-Cys Prx class have been identified and partially characterized In our article we give an introduction to redox-based drug development strategies against protozoal parasites and summarize the present knowledge on peroxiredoxin systems in Plasmodium.
细胞氧化还原代谢被认为与由弓形虫、锥虫、利什曼原虫和疟原虫等原生动物寄生虫引起的疾病的病理生理学有关。此外,氧化还原反应被认为在一些临床使用的抗寄生虫药物的作用和耐药性中起主要作用。有趣的是,疟原虫中不存在抗氧化酶过氧化氢酶和谷胱甘肽过氧化物酶,这表明硫氧还蛋白系统在氧化还原控制中起关键作用。除了一种谷胱甘肽过氧化物酶样硫氧还蛋白过氧化物酶和一种具有轻微过氧化物酶活性的谷胱甘肽S-转移酶外,恶性疟原虫(热带疟疾的病原体)还拥有四种经典的过氧化物还原酶:已鉴定并部分表征了两种典型的2-半胱氨酸过氧化物还原酶类过氧化物还原酶、一种与非典型2-半胱氨酸过氧化物还原酶类同源的1-半胱氨酸过氧化物还原酶,以及一种1-半胱氨酸过氧化物还原酶类过氧化物还原酶。在我们的文章中,我们介绍了针对原生动物寄生虫的基于氧化还原的药物开发策略,并总结了目前关于疟原虫过氧化物还原酶系统的知识。