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首页> 外文期刊>PLOS Neglected Tropical Diseases >Functional Characterization of Peroxiredoxins from the Human Protozoan Parasite Giardia intestinalis
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Functional Characterization of Peroxiredoxins from the Human Protozoan Parasite Giardia intestinalis

机译：人类原生动物寄生贾第虫肠道过氧化物酶的功能表征

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The microaerophilic protozoan parasite Giardia intestinalis, causative of one of the most common human intestinal diseases worldwide, infects the mucosa of the proximal small intestine, where it has to cope with O2 and nitric oxide (NO). Elucidating the antioxidant defense system of this pathogen lacking catalase and other conventional antioxidant enzymes is thus important to unveil novel potential drug targets. Enzymes metabolizing O2, NO and superoxide anion (O2??) have been recently reported for Giardia, but it is yet unknown how the parasite copes with H2O2 and peroxynitrite (ONOO?). Giardia encodes two yet uncharacterized 2-cys peroxiredoxins (Prxs), GiPrx1a and GiPrx1b. Peroxiredoxins are peroxidases implicated in virulence and drug resistance in several parasitic protozoa, able to protect from nitroxidative stress and repair oxidatively damaged molecules. GiPrx1a and a truncated form of GiPrx1b (deltaGiPrx1b) were expressed in Escherichia coli, purified and functionally characterized. Both Prxs effectively metabolize H2O2 and alkyl-hydroperoxides (cumyl- and tert-butyl-hydroperoxide) in the presence of NADPH and E. coli thioredoxin reductase/thioredoxin as the reducing system. Stopped-flow experiments show that both proteins in the reduced state react with ONOO? rapidly (k?=?4×105 M?1 s?1 and 2×105 M?1 s?1 at 4°C, for GiPrx1a and deltaGiPrx1b, respectively). Consistent with a protective role against oxidative stress, expression of GiPrx1a (but not deltaGiPrx1b) is induced in parasitic cells exposed to air O2 for 24 h. Based on these results, GiPrx1a and deltaGiPrx1b are suggested to play an important role in the antioxidant defense of Giardia, possibly contributing to pathogenesis.
机译：引起全球人类最常见肠道疾病之一的微需氧原生动物寄生虫贾第鞭毛虫（Giardia intestinalis）感染了近端小肠的粘膜，必须应对其中的O2和一氧化氮（NO）。因此，阐明缺乏过氧化氢酶和其他常规抗氧化酶的这种病原体的抗氧化防御系统对于揭示新的潜在药物靶标很重要。贾第鞭毛虫最近已报道了可代谢O2，NO和超氧阴离子（O2 ??）的酶，但尚不知道该寄生虫如何与H2O2和过氧亚硝酸盐（ONOO？）结合。贾第虫（Giardia）编码两个尚未表征的2-cys过氧化物酶（Prxs），即GiPrx1a和GiPrx1b。过氧化物氧还蛋白是过氧化物酶，在几种寄生虫原生动物中均具有毒力和耐药性，能够保护免受硝基氧化胁迫并修复氧化损伤的分子。 GiPrx1a和GiPrx1b的截短形式（deltaGiPrx1b）在大肠杆菌中表达，纯化并进行功能表征。在NADPH和大肠杆菌硫氧还蛋白还原酶/硫氧还蛋白作为还原系统的情况下，两种Prx均可有效代谢H2O2和烷基氢过氧化物（枯基和叔丁基氢过氧化物）。停流实验表明，两种还原态的蛋白质都与ONOO？反应。快速（在4°C下，对于GiPrx1a和deltaGiPrx1b，k？=？4×105 M？1 s？1和2×105 M？1 s？1）。与抗氧化应激的保护作用一致，在暴露于空气中24小时的寄生细胞中诱导了GiPrx1a（但不是deltaGiPrx1b）的表达。根据这些结果，建议GiPrx1a和deltaGiPrx1b在贾第虫的抗氧化防御中起重要作用，可能有助于发病。

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