Nuclear protein HMGN2 attenuates pyocyanin-induced oxidative stress via Nrf2 signaling and inhibits Pseudomonas aeruginosa internalization in A549 cells

• Published in: Free radical biology & medicine 2017-07, Vol.108, p.404-417
• Main Authors: Liu, Keyun, Wang, Xinyuan, Sha, Kaihui, Zhang, Fumei, Xiong, Feng, Wang, Xiaoying, Chen, Junli, Li, Jingyu, Churilov, Leonid P., Chen, Shanze, Wang, Yi, Huang, Ning
• Format: Article
• Language: English
• Subjects: A549 Cells; Actin cytoskeleton; Actin Cytoskeleton - metabolism; Bacterial Adhesion; Calcium Signaling; Cell Nucleus; Energy Metabolism; HMGN2; HMGN2 Protein - metabolism; Humans; Lung Diseases - metabolism; Lung Diseases - microbiology; NF-E2-Related Factor 2 - metabolism; Nrf2; Oxidative Stress; Phenazines - pharmacology; Protein Transport; Pseudomonas aeruginosa; Pseudomonas aeruginosa - physiology; Pseudomonas Infections - metabolism; Pyocyanin; Pyocyanine - metabolism; Reactive Oxygen Species - metabolism; Respiratory Mucosa - metabolism; Respiratory Mucosa - pathology; ROS
• ISSN: 0891-5849; 1873-4596
• DOI: 10.1016/j.freeradbiomed.2017.04.007

Pyocyanin (PCN, 1-hydroxy-5-methyl-phenazine) is one of the most essential virulence factors of Pseudomonas aeruginosa (PA) to cause various cytotoxic effects in long-term lung infectious diseases, however the early effect of this bacterial toxin during PA infection and subsequent autonomous immune response in host cells have not been fully understood yet. Our results display that early onset of PCN stimulates Pseudomonas aeruginosa PAO1 adhesion and invasion in A549 cells via ROS production. Non-histone nuclear protein HMGN2 is found to be involved in the regulation of PCN-induced oxidative stress by promoting intracellular ROS clearance. Mechanistically, HMGN2 facilitates nuclear translocation of transcription factor Nrf2 upon PCN stimulation and in turn elevates antioxidant gene expression. We also found that actin cytoskeleton dynamics is targeted by ROS, which is to be exploited by PAO1 for host cell internalization. HMGN2 regulates actin skeleton rearrangement in both PCN-dependent and independent manners and specifically attenuates PCN-mediated PAO1 infection via ROS elimination. These results uncover a novel link between nuclear protein HMGN2 and Nrf2-mediated cellular redox circumstance and suggest roles of HMGN2 in autonomous immune response to PA infection. [Display omitted] •PCN facilitates PAO1 infection in A549 cells via intracellular ROS production.•HMGN2 is involved in the regulation of PCN-induced intracellular ROS level and calcium flux in A549 cells.•HMGN2 facilitates PCN-induced Nrf2 nuclear translocation and regulates PCN-mediated phase II antioxidant enzyme function.•HMGN2 regulates actin cytoskeleton rearrangement and PCN-mediated PAO1 invasion in A549 cells under oxidative stress.