Thioredoxin Protects Fetal Type II Epithelial Cells From Hyperoxia-Induced Injury
Thioredoxin Protects Fetal Type II Epithelial Cells From Hyperoxia-Induced Injury
复制标题
硫氧还蛋白保护胎儿 II 型上皮细胞免受高氧诱导的损伤
DOI：
10.1002/ppul.21307
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发表时间：
2010-12-01
影响因子：
3.1
通讯作者：
Pan, Rui
中科院分区：
文献类型：
--
作者：
Chen, Yan;Chang, Liwen;Pan, Rui
众所周知，氧中毒是导致支气管肺发育不良（早产儿的一种慢性肺病）的主要因素之一。硫氧还蛋白（Trx）是一种抗氧化剂，可防止氧化应激诱导的细胞死亡，提示其在支气管肺发育不良中具有潜在的治疗作用。本研究的目的是确定Trx在高氧诱导的肺泡上皮细胞损伤的发病机制中的作用。胎鼠肺泡II型上皮细胞暴露于体外高氧在存在或不存在重组人Trx（rhTrx 2 μ g/ml）。通过3-（4，5-二甲基噻唑-2-基）-2，5-二苯基溴化四唑测定来评估细胞活力。流式细胞术检测细胞凋亡和活性氧（ROS）水平。Western blotting检测丝裂原活化蛋白激酶（MAPK）和磷脂酰肌醇3-激酶-Akt（PI3K-Akt）通路的激活。我们还研究了rhTrx对以下抗氧化剂（超氧化物歧化酶，过氧化氢酶和谷胱甘肽过氧化物酶）的影响。Trx显着减少高氧诱导的细胞死亡，增加细胞活力。此外，在高氧条件下，在II型细胞中的ROS产生被rhTrx抑制。我们证明rhTrx通过维持细胞外信号调节激酶和PI3K的激活，以及降低c-Jun N-末端蛋白激酶和p38的激活来保护II型细胞免受高氧损伤。rhTrx还能提高高氧暴露的Ⅱ型细胞锰超氧化物歧化酶和谷胱甘肽过氧化物酶的活性。总之，这些结果表明，rhTrx管理显着减弱高氧诱导的II型细胞损伤，通过减少ROS的产生，抗氧化活性的提高和MAPK和PI3K-Akt信号通路的调节。小儿肺醇。2010; 45：1192 - 1200. (C)2010 Wiley-Liss，Inc.
Oxygen toxicity is known to be one of the major contributors to bronchopulmonary dysplasia, a chronic lung disease in premature infants. Thioredoxin (Trx) is an antioxidant that prevents oxidative stress-induced cell death, suggesting a potential therapeutic role in bronchopulmonary dysplasia. The aim of this study was to determine the role of Trx in the pathogenesis of hyperoxia-induced alveolar epithelial cell injury. Alveolar type II epithelial cells from fetal rat lung were exposed to hyperoxia in vitro in the presence or absence of recombinant human Trx (rhTrx 2 mu g/ml). Cell viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay. Apoptosis and levels of reactive oxygen species (ROS) were measured by flow cytometry. Activation of mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase-Akt (PI3K-Akt) pathways were detected by Western blotting. We also investigated the effects of rhTrx on the following antioxidants (superoxide dismutase, catalase, and glutathione peroxidase). Trx significantly reduced hyperoxia-induced cell death and increased cell viability. In addition, ROS generation in type II cells was inhibited by rhTrx under hyperoxic conditions. We demonstrated that rhTrx protected type II cells against hyperoxic injury via sustaining the extracellular signal regulated kinase and PI3K activation, and decreasing of c-Jun N-terminal protein kinase and p38 activation. The results also showed manganese superoxide dismutase and glutathione peroxidase activities were increased by rhTrx in type II cells exposed to hyperoxia. Taken together, these results demonstrate that rhTrx administration markedly attenuates hyperoxia-induced type II cell injury through reduction of ROS generation, elevation of antioxidant activities and regulation of both MAPK and PI3K-Akt signaling pathways. Pediatr Pulmonol. 2010; 45:1192-1200. (C) 2010 Wiley-Liss, Inc.