Li Y, Zhang W, Mantell L L, Kazzaz J A, Fein A M, Horowitz S
The CardioPulmonary Research Institute, Winthrop-University Hospital, State University of New York at Stony Brook School of Medicine, Mineola, New York 11501, USA.
J Biol Chem. 1997 Aug 15;272(33):20646-9. doi: 10.1074/jbc.272.33.20646.
Oxidative insults that are lethal to epithelial cells kill either via apoptosis or necrosis. Nuclear factor-kappaB (NF-kappaB) is a redox-sensitive transcription factor that is activated by oxidative insult, and NF-kappaB activation can protect cells from apoptosis. To test if NF-kappaB can protect from necrotic cell death caused by high levels of molecular O2 (hyperoxia), we exposed human alveolar epithelial (A549) cells to hyperoxia. NF-kappaB was shown to be activated and was translocated to the nucleus within minutes. Nuclear translocation persisted over the course of several days, and the levels of NF-kappaB protein and mRNA increased as well. In hyperoxia, NF-kappaB regulation was independent of mitogen-activated protein kinase (MAPK). In sharp contrast, there was neither nuclear translocation of NF-kappaB nor any increase in expression after exposure to H2O2 at a concentration where this oxidant induces both MAPK and widespread apoptosis. Despite the activation and increased expression of NF-kappaB in hyperoxia, this oxidant remained lethal to the cells. These observations confirm the notion that apoptosis occurs in the absence of NF-kappaB activation but indicate that protection from cell death by NF-kappaB is probably limited to apoptosis.
对上皮细胞具有致死性的氧化损伤可通过凋亡或坏死的方式导致细胞死亡。核因子-κB（NF-κB）是一种对氧化还原敏感的转录因子，可被氧化损伤激活，且NF-κB的激活能够保护细胞免于凋亡。为了检测NF-κB是否能够保护细胞免受高浓度分子氧（高氧）引起的坏死性细胞死亡，我们将人肺泡上皮（A549）细胞暴露于高氧环境中。结果显示，NF-κB被激活，并在数分钟内转移至细胞核。细胞核转位在数天内持续存在，且NF-κB蛋白和mRNA水平也有所增加。在高氧环境中，NF-κB的调节独立于丝裂原活化蛋白激酶（MAPK）。与之形成鲜明对比的是，在暴露于过氧化氢（H2O2）时，尽管该氧化剂可诱导MAPK及广泛的凋亡，但既未出现NF-κB的细胞核转位，其表达也未增加。尽管在高氧环境中NF-κB被激活且表达增加，但这种氧化剂对细胞仍然具有致死性。这些观察结果证实了在没有NF-κB激活的情况下会发生凋亡这一观点，但表明NF-κB对细胞死亡的保护作用可能仅限于凋亡。
