Molecular and biochemical characterisation of a thioredoxin-linked thiolperoxidase system in the hydrogenosomes of the microaerophilic parasite Trichomonas vaginalis

微需氧寄生虫阴道毛滴虫氢酶体中硫氧还蛋白连接的硫醇过氧化物酶系统的分子和生化特征

• 批准号: 35388627
• 负责人: Privatdozentin Dr. Katrin Henze
• 金额: --
• 依托单位: Institut für Molekulare Evolution
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2007
• 资助国家: 德国
• 起止时间: 2006-12-31 至 2008-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/35388627?language=en
• 关键词: Molecular; biochemical; characterisation; thioredoxin; linked

With 180 million cases per year trichomoniasis is the most prevalent non-viral sexually transmitted infection world wide. The elevated risk of HIV infection connected to trichomoniasis and emergence of resistance to the most important drug in trichomoniasis treatment, metronidazole, has raised the need to study trichomonads, and especially their unique ATP-generating organelles, the hydrogenosomes, in detail. Hydrogenosomes, which harbour oxygen-sensitive enzymes like pyruvate:ferrodoxin oxidoreductase and Fe-hydrogenase, actively consume oxygen and produce H2O2 via oxygen-inducible Superoxide dismutase. Curiously, no enzymes capable of reducing H2O2 or alkyl peroxides have so far been identified in the organelles, raising the question how these highly deleterious compounds are detoxified in hydrogenosomes. In an ongoing proteome analysis of Trichomonas vaginalis hydrogenosomes we have identified two novel proteins with strong similarity to two putative prokaryotic peroxidases, rubrerythrin and the small periplasmic thiol peroxidase Tpx, which seem to be differentially regulated under oxidative stress. Both Tpx and rubrerythrin were previously found in many prokaryotes but not in other eukaryotes, suggesting a significant prokaryotic contribution to the oxygen-detoxification system of trichomonad hydrogenosomes. We propose to analyse the biochemical activity of Tpx and its putative electron-donating system thioredoxin/thioredoxin reductase in hydrogenosomes, as well as transcriptional and translational regulation of these proteins under oxidative stess, in oder to understand the mechanisms of oxidative stress protection in hydrogenosomes of trichomonads.

滴虫病是世界上最普遍的非病毒性性传播感染，每年有1.8亿例。滴虫病与HIV感染风险升高有关，对滴虫病治疗中最重要的药物甲硝唑出现耐药性，这提高了详细研究滴虫，特别是其独特的atp生成细胞器氢酶体的必要性。氢酶体含有丙酮酸、铁氧还蛋白氧化还原酶和铁氢化酶等对氧敏感的酶，它们通过氧诱导的超氧化物歧化酶主动消耗氧气并产生H2O2。奇怪的是，到目前为止，在细胞器中还没有发现能够还原H2O2或烷基过氧化物的酶，这就提出了这些高度有害的化合物是如何在氢酶体中解毒的问题。在一项正在进行的阴道毛滴虫氢酶体蛋白质组学分析中，我们发现了两种新的蛋白质，它们与两种推测的原核过氧化物酶红赤菊酯和小的质周硫醇过氧化物酶Tpx非常相似，它们似乎在氧化应激下受到不同的调节。以前在许多原核生物中发现了Tpx和红赤菊酯，但在其他真核生物中没有发现，这表明原核生物对毛滴虫氢酶体的氧解毒系统有重要贡献。我们建议通过分析Tpx及其可能的供电子系统硫氧还蛋白/硫氧还蛋白还原酶在氢化酶体中的生化活性，以及这些蛋白在氧化应激下的转录和翻译调控，以了解毛滴虫氢化酶体的氧化应激保护机制。