Liu Xiaoli, Yang Tuo, Sun Tieying, Shao Kuiqing
Department of Respiratory Medicine, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, P.R. China.
Department of Neurology, University of Pittsburgh, Pittsburgh, PA 15260, USA.
Mol Med Rep. 2017 Feb;15(2):813-818. doi: 10.3892/mmr.2016.6045. Epub 2016 Dec 14.
Sirtuin1 (SIRT1) is an NAD+‑dependent deacetylase that exhibits multiple biological functions, including cell differentiation inhibition, transcription regulation, cell cycle regulation and anti‑apoptosis. Lipopolysaccharides (LPS) are crucial virulence factors produced by Pseudomonas aeruginosa and serve an important role in adjusting the interactions between the host and the pathogen. However, the effect of SIRT1 in the regulation of LPS‑induced A459 human alveolar epithelial cells (AECs) oxidative stress remains unclear. The cellular reactive oxygen species (ROS) production was examined in A549 cells that were supplemented with LPS. Relative cell signaling pathway proteins were further investigated by western blot analysis. It was identified that LPS downregulated SIRT1 expression, however, upregulated ROS generation, which was associated with the increase of nuclear factor (NF)‑κB and acetyl‑NF‑κB. Activation of SIRT1 by resveratrol significantly reversed the effects of LPS on A549 cells. By contrast, inhibition of SIRT1 by nicotinamide had the opposite effects that enhance cell ROS production. Thus, the results indicated that SIRT1 serves an important role in the regulation of oxidative stress induced by LPS in human AECs.
沉默调节蛋白1（SIRT1）是一种依赖烟酰胺腺嘌呤二核苷酸（NAD⁺）的去乙酰化酶，具有多种生物学功能，包括抑制细胞分化、调节转录、调控细胞周期和抗细胞凋亡。脂多糖（LPS）是铜绿假单胞菌产生的关键毒力因子，在调节宿主与病原体之间的相互作用中发挥重要作用。然而，SIRT1在调节LPS诱导的A459人肺泡上皮细胞（AECs）氧化应激中的作用仍不清楚。在补充了LPS的A549细胞中检测细胞活性氧（ROS）的产生。通过蛋白质免疫印迹分析进一步研究相关细胞信号通路蛋白。结果发现，LPS下调了SIRT1的表达，但上调了ROS的生成，这与核因子（NF）-κB和乙酰化NF-κB的增加有关。白藜芦醇激活SIRT1可显著逆转LPS对A549细胞的影响。相反，烟酰胺抑制SIRT1则产生相反的效果，即增强细胞ROS的产生。因此，结果表明SIRT1在调节LPS诱导的人AECs氧化应激中起重要作用。
