NF-κB mediates the adaptation of human U937 cells to hydrogen peroxide

• Published in: Free radical biology & medicine 2001-03, Vol.30 (5), p.563-571
• Main Authors: Kim, Do Kyun, Cho, Eun Sook, Lee, Byung Ryong, Um, Hong-Duck
• Format: Article
• Language: English
• Subjects: Adaptation; Adaptation, Physiological; Cell death; DNA Fragmentation - drug effects; Free radicals; Humans; Hydrogen peroxide; Hydrogen Peroxide - metabolism; Hydrogen Peroxide - toxicity; I-kappa B Kinase; NF-^KB protein; NF-kappa B - metabolism; NF-κB; Oxidative Stress; oxygen; Protein-Serine-Threonine Kinases - genetics; Protein-Serine-Threonine Kinases - metabolism; Reactive Oxygen Species - metabolism; Sphingosine - analogs & derivatives; Sphingosine - pharmacology; U937 Cells
• ISSN: 0891-5849; 1873-4596
• DOI: 10.1016/S0891-5849(00)00504-9

Low doses of oxidative stress can induce cellular resistance to subsequent higher doses of the same stress. By using human U937 leukemia cells, we previously demonstrated that H 2O 2 can induce such an adaptive response without elevating the cellular capacity to degrade H 2O 2, and were able to confer the cells a cross-resistance to an H 2O 2-independent lethal stimulus, C 2-ceramide. In this study, it was found that the adaptation is accompanied by the translocation of cytoplasmic NF-κB to the nuclei. This event was promoted or abolished when either IKKα or a dominant negative mutant of IκB, respectively, was overexpressed. The overexpression of IKKα also resulted in the suppression of H 2O 2-induced cell death and DNA fragmentation, whereas these events were accelerated by the expression of the IκB mutant. The protective effect of IKKα was accompanied neither by an elevation of protein levels of various antioxidant enzymes such as catalase, superoxide dismutase, and glutathione peroxidase, nor by an increase in the cellular capacity to consume H 2O 2. Moreover, the overexpression of IKKα resulted in an enhancement of H 2O 2-induced resistance to C 2-ceramide. The overall data suggest that NF-κB mediates the H 2O 2 adaptation induced in a manner independent of H 2O 2-degrading activity.