MitoQ protects against hyperpermeability of endothelium barrier in acute lung injury via a Nrf2-dependent mechanism

• DOI: 10.1016/j.redox.2021.101936
• Publication Date: 2021-03-07T17:20:33Z
• Authors: Mengyuan Cen; Wei Ouyang; Wanying Zhang; Liping Yang; Xiuhui Lin; Min Dai; Huiqun Hu; Huifang Tang; Hongyun Liu; Jingyan Xia; Feng Xu
• Keywords: Mitochondrial ROS

Recently, numerous evidence has revealed that excessive reactive oxygen species (ROS) production and mitochondrial disruption during acute lung injury (ALI) its most severe form, respiratory distress syndrome (ARDS) will aggravate the inflammatory process. To identify whether antioxidation can be one of treatment strategies this progress, we chose mitoQ, a mitochondria-targeted antioxidant was proved to effective in reducing ROS generated mitochondria, as scavenger investigate role ALI. We demonstrated overoxidation occurred process ALI, which could reduced by mitoQ. In meantime, apoptosis endothelial cells ALI mice, accompanied hyperpermeability pulmonary vascular impaired function, partially reversed following an intraperitoneal injection Moreover, vitro study, lipopolysaccharides (LPS) induced production, dysfunction human microvascular (HPMECs), were rectified explore underlying mechanisms, proceeded RNA-sequencing found significantly upregulated expression musculoaponeurotic fibrosarcoma F (MafF) mitoQ treated group. Additionally, inhibited degradation increased nuclear translocation NF-E2-related factor 2 (Nrf2) downstream response elements (AREs), such heme oxygenase (HO)-1 NAD(P)H:quinone oxidoreductase (NQO)-1. This effect abolished transfecting HPMECs with Nrf2 or Maff siRNA. deficient protective effects on LPS model largely vanished. Taken together, these results provide insights into how exerts beneficial via maintaining hemostasis, inhibiting apoptosis, attenuating regulating inflammation Nrf2-MafF/ARE pathway.