Nuclear Factor Kb: An Oxidative Stress-Responsive Transcription Factor of Eukaryotic Cells (A Review)

Abstract

NF-kB is a multiprotein complex that can activate a great variety of genes involved in early defence reactions of higher organisms. In nonstimulated cells, NF-kB resides in the cytoplasm in an inactive complex with the inhibitor IkB. Pathogenic stimuli cause release of IkB and allow NF-kB to enter the nucleus, bind to DNA control elements and, thereby, induce the synthesis of mRNA. A puzzling feature of NF-kB is that its activation is triggered by a great variety of agents. These include the cytokines interleukin-1 and tumor necrosis factor, viruses, double-stranded RNA, endotoxins, phorbol esters, UV light and ionizing radiation. We recently found that also low concentrations of H2O2 activate NF-kB and that various antioxidants prevent the induction by H2O2. Subsequent analysis revealed that antioxidants not only suppress the activation of NF-kB by H2O2 but by all other inducers tested so far. In this review, we will discuss the evidences that NF-kB is an oxidative stress-responsive transcription factor of higher eukaryotic cells.