[Akt/SIRT3-dependent mitochondrial autophagy inhibits apoptosis of alveolar epithelial cells and alleviates hyperoxia-induced acute lung injury].

OBJECTIVE: To investigate the role and underlying mechanism of the protein kinase B (Akt)/sirtuin 3 (SIRT3) signaling pathway in hyperoxia-induced acute lung injury (HALI). METHODS: -induced apoptosis. SIRT3 was further knocked down to determine whether it functions downstream of Akt in this protective pathway. RESULTS: +SC-79+siSIRT3) increased apoptosis rate, cleaved caspase-3, Bax, and p62 [apoptosis rate: (10.30±0.96)% vs. (8.82±0.95)%, cleaved caspase-3 (cleaved caspase-3/GAPDH): 0.69±0.05 vs. 0.44±0.05, Bax (Bax/GAPDH): 0.99±0.06 vs. 0.49±0.04, p62 (p62/GAPDH): 0.59±0.06 vs. 0.38±0.04, all P<0.05], and decreased SIRT3, Bcl-2, and Beclin-1 [SIRT3 (SIRT3/GAPDH): 0.48±0.05 vs. 0.68±0.04, Bcl-2 (Bcl-2/GAPDH): 0.64±0.05 vs. 0.78±0.05, Beclin-1 (Beclin-1/GAPDH): 0.68±0.04 vs. 0.79±0.04, all P<0.05]. These findings indicate that SIRT3 knockdown attenuates SC-79-induced mitophagy and enhances apoptosis, supporting SIRT3 as an important downstream effector of the Akt pathway. CONCLUSIONS: Activation of the Akt/SIRT3 signaling pathway promotes mitophagy to inhibit alveolar epithelial cell apoptosis, thereby attenuating HALI.