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KMID : 0620920120440080513
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Experimental & Molecular Medicine
2012 Volume.44 No. 8 p.513 ~ p.520
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Transient exposure to hydrogen peroxide inhibits the ubiquitination of phosphorylated IκBα in TNFα-stimulated HEK293 cells
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Lee Ye-Ji
Choi Jin
Ha Kyung-Ho
Jue Dae-Myung
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Abstract
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During ischemia-reperfusion injury, brief pre-exposure to oxidative stress renders organs resistant to subsequent severe damage. NF-κB is a transcription factor that is involved in reperfusion-induced inflammatory and immune responses. The activity of NF-κB has been shown to be modulated by oxidative stress in various cell types through different pathways. We studied the effect of pre-exposure to oxidative stress on subsequent NF-κB activation in TNFα-stimulated HEK293 cells. The cells were transiently exposed to 0.5 mM H2O2 for 20 min, prior to stimulation with TNFα, and the subsequent expression of NF-κB-dependent genes and the levels of NF-κB signaling molecules were measured. Pre-exposure to H2O2 significantly delayed the TNFα-induced expression of an NF-κB reporter gene and inflammatory proteins (intercellular adhesion molecule-1 and IL-1β). The degradation of inhibitor of NF-κB α (IκBα) and the nuclear translocation of NF-κB were also delayed by H2O2 treatment, whereas IκBα phosphorylation and IκB kinase activity were not changed. When we examined the ubiquitin/proteosome pathway in H2O2-treated cells, we could not detect significant changes in proteosomal peptidase activities, but we were able to detect a delay of IκBα poly-ubiquitination. Our results suggest that transient exposure to oxidative stress temporally inhibits NF-κB-dependent gene expression by suppressing the poly-ubiquitination of phosphorylated IκBα in HEK293 cells.
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KEYWORD
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hydrogen peroxide, inflammation, NF-κB, proteasome endopeptidase complex, reactive oxygen species, reperfusion injury, ubiquitin
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