Nuclear factor-kappaB is activated by hyperoxia but does not protect from cell death.
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.
Li
Y
Y
The CardioPulmonary Research Institute, Winthrop-University Hospital, State University of New York at Stony Brook School of Medicine, Mineola, New York 11501, USA.
Zhang
W
W
Mantell
L L
LL
Kazzaz
J A
JA
Fein
A M
AM
Horowitz
S
S
D017209:Apoptosis; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity; D016328:NF-kappa B / Q000378:metabolism*; D010100:Oxygen / Q000633:toxicity*; D012333:RNA, Messenger / Q000032:analysis; D014407:Tumor Cells, Cultured
D016328:NF-kappa B; D012333:RNA, Messenger; D006861:Hydrogen Peroxide; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D010100:Oxygen