24-Dehydrocholesterol Reductase alleviates oxidative damage-induced apoptosis in alveolar epithelial cells via regulating Phosphatidylinositol-3-Kinase/Protein Kinase B activation

Apoptosis of alveolar epithelial cells during acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is a critical pathological event that seriously endangers the health of patients. Suppressing apoptosis of alveolar epithelial cells was shown to alleviate functional damage of lung, and modulator of the reactive oxygen species (ROS)-induced apoptosis becomes a promising approach to the ALI therapy. Previous little studies showed that DHCR24 possessed anti-oxidative and anti-apoptotic property in ALI. Thus, H(2)O(2) was utilized to mimic oxidative damage in vitro in alveolar epithelial cell line A549 in the present study. Our results exhibited that H(2)O(2) treatment of A549 cells reduced the level of SOD and increased the level of ROS. Moreover, H(2)O(2) inhibited Bcl-2 expression in A549 cells, but increased Bax and the activity of Caspase-3. In addition, the apoptosis rate in the H(2)O(2) treatment group also increased significantly. And the expression of 24-dehydrocholesterol reductase (DHCR24) was markedly reduced in the H(2)O(2) treatment group. Overexpression of DHCR24 can remarkably inhibit H(2)O(2)-induced oxidative stress and apoptosis. We found that overexpression of DHCR24 increased the phosphorylation level of PI3K and AKT, however, the PI3K inhibitor LY294002 (LY) eliminated the protective effect of DHCR24 in ALI. DHCR24 was down-regulated in H(2)O(2)-induced ALI, and overexpression of DHCR24 could inhibit H(2)O(2)-induced oxidative stress and apoptosis of A549 cells by activating the Phosphatidylinositol-3-Kinase/Protein Kinase B (PI3K/AKT) signaling pathway. The above exhibited a protective effect of DHCR24 on alveolar epithelial cells exposed to oxidative stress-mediated apoptosis and provided a novel therapeutic method for ALI.