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  • Title: Propofol reduces hypoxia‑induced autophagic cell death through downregulating HIF 1α in alveolar epithelial type II cells of rats.
    Author: Ning HJ, Yuan HB, Xu HT, He XY.
    Journal: Mol Med Rep; 2017 Aug; 16(2):1509-1515. PubMed ID: 28586054.
    Abstract:
    Propofol (2,6‑diisopropylphenol) exerts protective effects on alveolar epithelial type II (ATII) cells, partly through attenuating hypoxia‑induced apoptosis. Autophagy is involved in the activation of apoptosis. Therefore, the present study investigated the modulating effect of propofol against autophagy in ATII cells under hypoxia. Western blot analysis was performed to detect the protein expression of the autophagy molecular marker, microtubule‑associated protein 1 light chain 3 (LC3)‑II, under various conditions. The effects of propofol on the accumulation of other autophagy‑associated proteins and apoptosis‑associated proteins were also determined using western blot analysis. The interactions between proteins were determined by co‑immunoprecipitation. Apoptosis of the ATII cells was monitored using FITC‑conjugated AV/PI staining. Furthermore, hypoxia‑inducible factor 1α (HIF 1α) small interfering (si) RNA was designed to construct si‑HIF 1α ATII cells. The efficiency of interference was measured using reverse transcription‑quantitative polymerase chain reaction and western blot analyses. Following pre‑treatment with propofol, the hypoxia‑induced accumulation of LC3‑II, HIF 1α and B‑cell lymphoma‑2 interacting protein 3 (Bnip3) were markedly decreased, accompanied with the activation of mammalian target of rapamycin. In addition, cleaved‑poly ADP‑ribose polymerase was suppressed, and hypoxia‑induced autophagic cell death was inhibited by propofol pre‑treatment. HIF 1α was inhibited by si‑HIF 1α, which simultaneously suppressed Bnip3 and LC3‑II under hypoxia. Taken together, propofol reduced hypoxia‑induced autophagic cell death through reducing the expression of HIF 1α in ATII cells, indicating a novel strategy for modulating autophagy via propofol in hypoxic ATII cells.
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