NUCLEAR FACTOR-KAPPA-B IS ACTIVATED BY HYPEROXIA BUT DOES NOT PROTECTFROM CELL-DEATH

Oxidative insults that are lethal to epithelial cells kill either via apoptosis or necrosis. Nuclear factor-kappa B (NF-kappa B) is a redox- sensitive transcription factor that is activated by oxidative insult, and NF-kappa B activation can protect cells from apoptosis. To test if NF-kappa B can protect from necrotic cell death caused by high levels of molecular O-2 (hyperoxia), we exposed human alveolar epithelial (A 549) cells to hyperoxia. NF-kappa B was shown to be activated and was translocated to the nucleus within minutes. Nuclear translocation pers isted over the course of several days, and the levels of NF-kappa B pr otein and mRNA increased as well. In hyperoxia, NF-kappa B regulation was independent of mitogen-activated protein kinase (MAPK). In sharp c ontrast, there was neither nuclear translocation of NF-kappa B nor any increase in expression after exposure to H2O2 at a concentration wher e this oxidant induces both MAPK and widespread apoptosis. Despite the activation and increased expression of NF-kappa B in hyperoxia, this oxidant remained lethal to the cells. These observations confirm the n otion that apoptosis occurs in the absence of NF-kappa B activation bu t indicate that protection from cell death by NF-kappa B is probably l imited to apoptosis.