Nuclear factor-κB is activated by hyperoxia but does not protect from cell death

Abstract

Oxidative insults that are lethal to epithelial cells kill either via apoptosis or necrosis. Nuclear factor-κB (NF-κB) is a redox-sensitive transcription factor that is activated by oxidative insult, and NF-κB activation can protect cells from apoptosis. To test if NF-κB can protect from necrotic cell death caused by high levels of molecular O2 (hyperoxia), we exposed human alveolar epithelial (A549) cells to hyperoxia. NF-κB 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-κB protein and mRNA increased as well. In hyperoxia, NF-κB regulation was independent of mitogen-activated protein kinase (MAPK). In sharp contrast, there was neither nuclear translocation of NF-κB 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-κB in hyperoxia, this oxidant remained lethal to the cells. These observations confirm the notion that apoptosis occurs in the absence of NF-κB activation but indicate that protection from cell death by NF-κB is probably limited to apoptosis.