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首页> 外文期刊>Infection and immunity >Iron Superoxide Dismutases Targeted to the Glycosomes of Leishmania chagasi Are Important for Survival
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Iron Superoxide Dismutases Targeted to the Glycosomes of Leishmania chagasi Are Important for Survival

机译：铁的超氧化物歧化酶针对利什曼原虫的遗传糖体是重要的生存。

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Kinetoplastid glycosomes contain a variety of metabolic activities, such as glycolysis, β-oxidation of fatty acids, lipid biosynthesis, and purine salvage. One advantage of sequestering metabolic activities is the avoidance of cellular oxidative damage by reactive oxygen species produced as a by-product of metabolism. Little is known about how glycosomes themselves withstand these toxic metabolites. We previously isolated an iron superoxide dismutase from Leishmania chagasi that is expressed at low levels in the early logarithmic promastigote stage and increases toward the stationary promastigote and amastigote stages. We have since identified a second highly homologous Lcfesodb gene that is expressed at high levels in the early logarithmic promastigote stage and decreases toward the stationary promastigote and amastigote stages. Localization studies using green fluorescent protein fusions have revealed that LcFeSODB1 and LcFeSODB2 are localized within the glycosomes by the last three amino acids of their carboxyl termini. To better understand the specific role that FeSODB plays in parasite growth and survival, a single-allele knockout of the Lcfesodb1 gene was generated. The parasites with these genes exhibited a significant reduction in growth when endogenous superoxide levels were increased with paraquat in culture. Furthermore, the FeSODB1-deficient parasites exhibited a significant reduction in survival within human macrophages. Our results suggest that LcFeSODB plays an important role in parasite growth and survival by protecting glycosomes from superoxide toxicity.
机译：运动质体糖体包含多种代谢活性，例如糖酵解，脂肪酸的β-氧化，脂质生物合成和嘌呤挽救。隔离代谢活动的一个优点是避免了由于代谢副产物活性氧而引起的细胞氧化损伤。关于糖体自身如何抵抗这些有毒代谢物知之甚少。我们以前从 Leishmania chagasi 中分离了一种铁超氧化物歧化酶，该酶在对数前鞭毛前期阶段以低水平表达，并向固定前鞭毛前期和后鞭毛前期增加。此后，我们确定了第二个高度同源的 Lcfesodb 基因，该基因在对数前鞭毛体早期阶段以高水平表达，并向静止的前鞭毛体和鞭毛体阶段降低。使用绿色荧光蛋白融合物的定位研究表明，LcFeSODB1和LcFeSODB2通过其羧基末端的后三个氨基酸定位在糖体内。为了更好地了解FeSODB在寄生虫生长和存活中的特定作用，生成了 Lcfesodb1 基因的单等位基因敲除。当培养中的百草枯使内源性超氧化物水平升高时，具有这些基因的寄生虫表现出生长的显着降低。此外，FeSODB1缺陷型寄生虫在人类巨噬细胞内的生存率显着降低。我们的结果表明，LcFeSODB通过保护糖体免受超氧化物毒性的影响，在寄生虫的生长和存活中起着重要作用。

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