Nf-κB protects lung epithelium against HYPEROXIA-INDUCED nonapoptotic cell death-oncosis
Nf-κB protects lung epithelium against HYPEROXIA-INDUCED nonapoptotic cell death-oncosis
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DOI：
10.1016/j.freeradbiomed.2004.08.007
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发表时间：
2004-11-15
影响因子：
7.4
通讯作者：
Mantell, UL
中科院分区：
文献类型：
--
作者：
Franek, WR;Morrow, DMP;Mantell, UL
长期暴露在高氧环境中会导致肺上皮细胞死亡和急性肺损伤。虽然在高氧培养的动物肺中观察到了凋亡和非凋亡的形态，但只有在高氧培养的转化的肺上皮中才记录到非凋亡性的细胞死亡。为了验证高氧动物肺的非凋亡特征是否是高氧的直接影响，从形态和生化两个方面测定了95%O-2暴露的人原代肺上皮细胞的死亡方式。与凋亡细胞的特征相反，高氧导致细胞核肿胀和细胞大小增加，但没有证据表明caspase-3活性或Annexin V掺入水平有任何增加。提示高氧可直接诱导原代肺上皮细胞非凋亡性死亡。尽管高氧诱导的非凋亡性细胞死亡与核因子-kappaB的激活有关，但目前尚不清楚核因子-kappaB的激活是否在非凋亡性细胞死亡中起因果作用。本研究表明，抑制核因子-kappaB的激活可以加速高氧诱导的原代和转化肺上皮细胞的死亡。与高氧条件下细胞存活率降低相对应的是，在NF-kappaB缺陷细胞中，MnSOD的水平也很低。这些结果表明，核因子-kappaB保护肺上皮细胞免受高氧诱导的非凋亡性细胞死亡。(C)2004 Elsevier Inc.保留所有权利。
Prolonged exposure to hyperoxia induces pulmonary epithelial cell death and acute lung injury. Although both apoptotic and nonapoptotic morphologies are observed in hyperoxic animal lungs, nonapoptotic cell death had only been recorded in transformed lung epithelium cultured in hyperoxia. To test whether the nonapoptotic characteristics in hyperoxic animal lungs are direct effects of hyperoxia, the mode of cell death was determined both morphologically and biochemically in human primary lung epithelium exposed to 95% O-2. In contrast to characteristics observed in apoptotic cells, hyperoxia induced swelling of nuclei and an increase in cell size, with no evidence for any augmentation in the levels of either caspase-3 activity or annexin V incorporation. These data suggest that hyperoxia can directly induce nonapoptotic cell death in primary lung epithelium. Although hyperoxia-induced nonapoptotic cell death was associated with NF-kappaB activation, it is unknown whether NF-kappaB activation plays any causal role in nonapoptotic cell death. This study shows that inhibition of NF-kappaB activation can accelerate hyperoxia-induced epithelial cell death in both primary and transformed lung epithelium. Corresponding to the reduced cell survival in hyperoxia, the levels of MnSOD were also low in NF-kappaB-deficient cells. These results demonstrate that NF-kappaB protects lung epithelial cells from hyperoxia-induced nonapoptotic cell death. (C) 2004 Elsevier Inc. All rights reserved.