Hydrogen protects against hyperoxia-induced apoptosis in type II alveolar epithelial cells via activation of PI3K/Akt/Foxo3a signaling pathway
Hydrogen protects against hyperoxia-induced apoptosis in type II alveolar epithelial cells via activation of PI3K/Akt/Foxo3a signaling pathway
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DOI：
10.1016/j.bbrc.2017.11.193
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发表时间：
2018-01-08
影响因子：
3.1
通讯作者：
Liu, Chengjun
中科院分区：
文献类型：
--
作者：
Wu, Dan;Liang, Mulin;Liu, Chengjun
氧化应激被认为是长时间高氧性肺损伤的关键调节因子，高氧性肺损伤导致肺泡上皮细胞损伤，最终导致支气管肺发育不良(BPD)。许多研究表明，氢在多种细胞中具有保护作用。然而，氢在BPD中拯救细胞免受氧化应激损伤的机制仍未完全阐明。本研究旨在评价氢气对高氧性肺损伤的影响，并探讨其可能的机制。原代培养的肺泡II型上皮细胞(AECII)分为4组：对照组(21%氧气)、高氧组(95%氧气)、高氧+氢组、高氧+氢+PI3K/Akt抑制剂LY294002组。用四甲基偶氮唑蓝(MTS)比色法和流式细胞仪(FCM)分别检测AECII细胞的增殖和凋亡。用定量聚合酶链式反应(Q-PCR)和蛋白质印迹分析检测基因和蛋白的表达。高氧刺激可降低P-Akt、P-FOXO3a、Cyclin D1和Bcl2的表达。高氧条件下Bim、Bax和Foxo3a水平升高，导致AECII细胞增殖受限和细胞凋亡。高氧的这些效应可被氢气预处理逆转。此外，氢的保护作用可被PI3K/Akt抑制剂LY294002消除。结果表明，氢通过抑制凋亡因子和促进抗凋亡因子的表达，对高氧诱导的AECII细胞具有保护作用。这些效应与PI3K/Akt/FOXO3a通路的激活有关。(C)2017 Elsevier Inc.保留所有权利。
Oxidative stress is regarded as a key regulator in the pathogenesis of prolonged hyperoxia-induced lung injury, which causes injury to alveolar epithelial cells and eventually leads to development of bronchopulmonary dysplasia (BPD). Many studies have shown that hydrogen has a protective effect in a variety of cells. However, the mechanisms by which hydrogen rescues cells from damage due to oxidative stress in BPD remains to be fully elucidated. This study sought to evaluate the effects of hydrogen on hyperoxia-induced lung injury and to investigate the underlying mechanism. Primary type II alveolar epithelial cells (AECIIs) were divided into four groups: control (21% oxygen), hyperoxia (95% oxygen), hyperoxia + hydrogen, and hyperoxia + hydrogen + LY294002 (a PI3K/Akt inhibitor). Proliferation and apoptosis of AECIIs were assessed using MTS assay and flow cytometry (FCM), respectively. Gene and protein expression were detected by quantitative polymerase chain reaction (q-PCR) and western blot analysis. Stimulation with hyperoxia decreased the expression of P-Akt, P-FoxO3a, cyclinD1 and Bcl-2. Hyperoxic conditions increased levels of Bim, Bax, and Foxo3a, which induced proliferation restriction and apoptosis of AECIIs. These effects of hyperoxia were reversed with hydrogen pretreatment. Furthermore, the protective effects of hydrogen were abrogated by PI3K/Akt inhibitor LY294002. The results indicate that hydrogen protects AECIIs from hyperoxia-induced apoptosis by inhibiting apoptosis factors and promoting the expression of anti-apoptosis factors. These effects were associated with activation of the PI3K/Akt/FoxO3a pathway. (C) 2017 Elsevier Inc. All rights reserved.