Abstract
Localization of phosphorylated (p)‑JNK to the mitochondria can lead to functional mitochondrial disorder, resulting in a decrease in energy supply and membrane potential, as well as an increase in reactive oxygen species production and apoptosis. JNK is involved in the occurrence of acute lung injury (ALI), and activation of the JNK pathway is one of the crucial factors resulting in injury. The aim of the present study was to investigate whether the JNK‑mitochondria (mitoJNK) location participated in the occurrence of ALI and acute respiratory distress syndrome (ALI/ARDS). The present study examined the activation of the JNK pathway, the content of JNK located on the mitochondria and the treatment effects of a cell‑permeable peptide Tat‑SabKIM1, which can selectively inhibit the location of JNK on mitochondria. The expression levels of proteins were detected by western blot analysis. Lung injuries were evaluated by histological examination, wet‑to‑dry weight ratios, and H2O2 and malondialdehyde concentrations in the lung tissues. Lung cells apoptosis was evaluated using TUNEL assay. The results demonstrated that JNK was phosphorylated and activated during seawater inhalation‑induced ALI/ARDS, not only in the routine JNK pathway but also in the mitoJNK pathway. It was also found that Tat‑SabKIM1 could specifically inhibit JNK localization to mitochondria and the activation of mitoJNK signaling. Furthermore, Tat‑SabKIM1 could inhibit Bcl‑2‑regulated autophagy and mitochondria‑mediated apoptosis. In conclusion, mitoJNK localization disrupted the normal physiological functions of the mitochondria during ALI/ARDS, and selective inhibition of JNK and mitochondrial SH3BP5 (also known as Sab) binding with Tat‑SabKIM1 can block deterioration from ALI/ARDS.