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

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

  • Free Radic Biol Med. 2017 Jul;108:404-417. doi: 10.1016/j.freeradbiomed.2017.04.007.
Keyun Liu 1,  Xinyuan Wang 2,  Kaihui Sha 3,  Fumei Zhang 4,  Feng Xiong 2,  Xiaoying Wang 2,  Junli Chen 2,  Jingyu Li 2,  Leonid P Churilov 5,  Shanze Chen 2,  Yi Wang 6,  Ning Huang 7
Affiliations

Affiliations

  • 1 Research Unit of Infection and Immunity, Department of Pathophysiology, West China College of Basic and Forensic Medicine, Sichuan University, Chengdu 610041, China; Department of Physiology, School of Medicine, Hubei University for Nationalities, Enshi 445000, China.
  • 2 Research Unit of Infection and Immunity, Department of Pathophysiology, West China College of Basic and Forensic Medicine, Sichuan University, Chengdu 610041, China.
  • 3 School of Nursing, Binzhou Medical University, Binzhou 256600, China.
  • 4 Experimental Center, Northwest University for Nationalities, Lanzhou 730030, China.
  • 5 Department of Pathology, Faculty of Medicine, Saint Petersburg State University, Saint Petersburg 199034, Russia; Saint Petersburg State Research Institute of Phthisiopulmonology, Saint Petersburg 191036, Russia.
  • 6 Research Unit of Infection and Immunity, Department of Pathophysiology, West China College of Basic and Forensic Medicine, Sichuan University, Chengdu 610041, China. Electronic address: [email protected].
  • 7 Research Unit of Infection and Immunity, Department of Pathophysiology, West China College of Basic and Forensic Medicine, Sichuan University, Chengdu 610041, China. Electronic address: [email protected].
PMID: 28408162 DOI: 10.1016/j.freeradbiomed.2017.04.007
Abstract

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.

Keywords

Actin cytoskeleton; HMGN2; Nrf2; Pseudomonas aeruginosa; Pyocyanin; ROS.

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