Protective effect of SIRT3 on acute lung injury by increasing manganese superoxide dismutase-mediated antioxidation.

Abstract

Prolonged exposure to hyperoxia results in acute lung injury (ALI). Pulmonary damage caused by oxygen toxicity occurs due to the generation of reactive oxygen species and subsequent formation of more potent oxidants. The present study demonstrated that sirtuin 3 (SIRT3) may attenuate hyperoxia‑induced ALI due to its potential antioxidative effect. In the present study, a hyperoxia‑induced acute lung injury mouse model, reverse transcription‑quantitative polymerase chain reaction, western blotting, retroviral mediated gene over‑expression and knockdown assays revealed that the expression of SIRT3 in the lung tissue of mice with hyperoxia‑induced ALI was decreased and overexpression of SIRT3 may significantly reduce hyperoxia‑induced ALI, as reflected by decreases in protein concentration, infiltrated neutrophils in bronchoalveolar lavage (BAL) fluid and wet/dry ratio of lung tissues. Furthermore, overexpression of SIRT3 increased the protein levels and enzymatic activity of manganese superoxide dismutase (MnSOD), and inhibited oxidative stress in the lungs of ALI mice. Additionally, the current study demonstrated that SIRT3 promoted the expression of MnSOD, and this regulation was crucial for the protective effect of SIRT3 on hyperoxia‑induced ALI. In summary, the results of the current study indicated that SIRT3 overexpression may effectively ameliorate hyperoxia‑induced ALI in mice, which indicates a potential application for SIRT3‑based gene therapy to treat clinical adult respiratory distress syndrome.