Abstract P241: Irisin Protects Mitochondria Function During Pulmonary Ischemia Reperfusion Injury

Abstract

Background: Ischemia and reperfusion (I/R) induced lung injury is one of the most important and common causes of early and high morbidity and mortality. The mitochondrial damage of alveolar epithelium cells leads to further damage in lung I/R by augmented ROS activity and inflammation. Previous study show a humoral myokine, irisin, has been found stimulate mitochondrial biogenesis. We hypothesize irisin might protect lung from I/R injury. Methods: The lung I/R injury model was performed on C57BL/6J mice. The pulmonary protection of exogenous irisin was indicated by lung edema and function measurement, and the survival of mice. The localization of irisin was measured by immunohistochemistry and immunofluorescence staining. And the protective effect of irisin to mitochondrial was demonstrated by ATP production, ROS production, mitochondria-dependent apoptosis measurement, and so on. Results: There was no endogenous irisin expression in the alveolar wall in normal mice. However, it is interesting to find that, irisin was in the alveoli after lung I/R injury. The increased irisin in lung might be from plasma, because in the mean time, the plasma irisin levels were decreased. Exogenous intravenous injection of irisin protect the lung from I/R injury. The protective effect might be via the protection on the mitochondria in lung, exogenous irisin was found to localize in the mitochondria, the impaired mitochondrial function in I/R mice was reversed after irisin treatment. Moreover, there was colocalization between the irisin and UCP2, exogenous irisin decreased the I/R-induced UCP2 degradation. The role of UCP2 on the protection of mitochondria is further confirmed in the in in-vivo experiment, inhibition of UCP2 or knockout of UCP2 would make the protection of irisin on lung function and mitochondrial function lost. Conclusions: Administration with exogenous irisin would alleviate the I/R damage, reduced the inflammatory and superoxide factors, ameliorated the mitochondrial dysfunction, via the binding of irisin and UCP2 in lung.