Peroxiredoxin-3 (Prdx3) is a mitochondrial protein of the thioredoxin family of antioxidant peroxidases and is the principal peroxidase responsible for metabolizing mitochondrial hydrogen peroxide. Recent reports have shown that mitochondrial reactive oxygen species (mROS) contribute to macrophage-mediated bactericidal activity in response to Toll-like receptors. Herein, we investigated the functional effect of Prdx3 in bactericidal activity. The mitochondrial localization of Prdx3 in HEK293T cells was confirmed by cell fractionation and confocal microscopy analyses. To investigate the functional role of Prdx3 in bactericidal activity, Prdx3-knockdown (Prdx3KD) THP-1 cells were generated. The mROS levels in Prdx3KD THP-1 cells were significantly higher than those in control THP-1 cells. Moreover, the mROS levels were markedly increased in response to lipopolysaccharide. Notably, the Salmonella enterica serovar Typhimurium infection assay revealed that the Prdx3KD THP-1 cells were significantly resistant to S. Typhimurium infection, as compared with control THP-1 cells. Taken together, these results indicate that Prdx3 is functionally important in bactericidal activity through the regulation of mROS.

中文翻译：

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Peroxiredoxin-3 通过调节线粒体活性氧种类参与杀菌活性

Peroxiredoxin-3 (Prdx3) 是抗氧化过氧化物酶硫氧还蛋白家族的一种线粒体蛋白，是负责代谢线粒体过氧化氢的主要过氧化物酶。最近的报告表明，线粒体活性氧 (mROS) 有助于巨噬细胞介导的杀菌活性，以响应 Toll 样受体。在此，我们研究了 Prdx3 在杀菌活性中的功能作用。通过细胞分级和共聚焦显微镜分析证实了 Prdx3 在 HEK293T 细胞中的线粒体定位。为了研究 Prdx3 在杀菌活性中的功能作用，产生了 Prdx3 敲低 (Prdx3KD) THP-1 细胞。Prdx3KD THP-1 细胞中的 mROS 水平显着高于对照 THP-1 细胞中的水平。而且，mROS 水平显着增加以响应脂多糖。值得注意的是，与对照 THP-1 细胞相比，肠道沙门氏菌血清型鼠伤寒沙门氏菌感染测定显示，Prdx3KD THP-1 细胞对鼠伤寒沙门氏菌感染具有显着抗性。总之，这些结果表明，Prdx3 通过调节 mROS 在杀菌活性中具有重要的功能。