Institute of Pathogenic Biology, Hengyang Medical College, Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control, University of South China, Hengyang 421001, China.
Institute of Pathogenic Biology, Hengyang Medical College, Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control, University of South China, Hengyang 421001, China.
Life Sci. 2021 Jul 15;277:119502. doi: 10.1016/j.lfs.2021.119502. Epub 2021 Apr 20.
Chlamydia trachomatis has evolved various strategies to alleviate oxidative stress of host cells to maintain their intracellular survival. However, the exact mechanism of anti-oxidative stress of C. trachomatis is still unclear. The activation of nuclear factor erythroid 2-related factor 2/quinone oxidoreductase (Nrf2/NQO1) signal pathway has been identified as an efficient antioxidant defensive mechanism used by host cells to counteract oxidative stress. Pgp3 is a pivotal virulence factor of C. trachomatis involved in intracellular survival. The aim of this study is to explore the role of Pgp3 on Nrf2/NQO1 signal pathway against oxidative stress.
After HeLa cells were stimulated with Pgp3 protein, Nrf2 location and the inclusion bodies of C. trachomatis were detected by indirect immunofluorescence, western blotting and Oxidative stress assay kits were used to separately determine the protein expression and the content of malondialdehyde (MDA), superoxide dismutase (SOD) and total antioxidant capacity (T-AOC) before and after the interference of Nrf-2 and NQO1.
Pgp3 promoted the nuclear translocation of Nrf2 to increase NQO1 expression and reduced oxidative stress induced by LPS to contribute to the survival of C. trachomatis. Inhibition of Nrf2/NQO1 signal pathway with Nrf2 inhibitor and down-regulation of NQO1 with siRNA-NQO1 suppressed oxidative stress resistance induced by Pgp3.
Here we found that Pgp3 alleviated oxidative stress to promote the infectivity of C. trachomatis through activation of Nrf2/NQO1 signal pathway, which provided a novel understanding of the effects of Pgp3 in the pathogenesis of C. trachomatis.
沙眼衣原体进化出各种策略来减轻宿主细胞的氧化应激，以维持其细胞内生存。然而，沙眼衣原体抗氧化应激的确切机制仍不清楚。核因子红细胞 2 相关因子 2/醌氧化还原酶（Nrf2/NQO1）信号通路的激活已被确定为宿主细胞抵抗氧化应激的一种有效的抗氧化防御机制。Pgp3 是沙眼衣原体的一个关键毒力因子，参与细胞内生存。本研究旨在探讨 Pgp3 对 Nrf2/NQO1 信号通路在对抗氧化应激中的作用。
用 Pgp3 蛋白刺激 HeLa 细胞后，通过间接免疫荧光、Western blot 检测 Nrf2 定位和沙眼衣原体包涵体，分别用氧化应激检测试剂盒测定 Nrf-2 和 NQO1 干扰前后蛋白表达和丙二醛（MDA）、超氧化物歧化酶（SOD）和总抗氧化能力（T-AOC）的含量。
Pgp3 促进 Nrf2 的核转位，增加 NQO1 的表达，减轻 LPS 诱导的氧化应激，有助于沙眼衣原体的生存。用 Nrf2 抑制剂抑制 Nrf2/NQO1 信号通路和用 siRNA-NQO1 下调 NQO1 抑制了 Pgp3 诱导的氧化应激抵抗。
我们发现 Pgp3 通过激活 Nrf2/NQO1 信号通路减轻氧化应激，促进沙眼衣原体的感染力，为 Pgp3 在沙眼衣原体发病机制中的作用提供了新的认识。
