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RECEPTORS AND SIGNAL TRANSDUCTION

Exposure to hydrogen peroxide diminishes NF-B activation, IB- degradation, and proteasome activity in neutrophils

¹Department of Medicine, ²Center for Free Radical Biology, University of Alabama, Birmingham, Alabama

Submitted 12 December 2006 ; accepted in final form 22 March 2007

Although ROS can participate in modulating the activity of the transcriptional factor NF-B and expression of NF-B-dependent genes, the mechanisms involved and the roles of specific ROS have not been fully determined. In particular, individual ROS appear to have differing effects on NF-B activation dependent on the cell population studied. In the present study, we examined the ability of H₂O₂ to affect NF-B activation in LPS-stimulated murine neutrophils and macrophages. Exposure of bone marrow or peritoneal neutrophils to H₂O₂ was associated with reduced nuclear translocation of NF-B and decreased production of the NF-B-dependent cytokines TNF- and macrophage inhibitory protein-2. H₂O₂ treatment resulted in diminished trypsin- and chymotrypsin-like proteasome activity. The degradation of IB- normally found in LPS-treated neutrophils was prevented when H₂O₂ was added to cell cultures. In contrast to the effects found in neutrophils, H₂O₂ did not affect chymotrypsin-like proteasomal activity or cytokine production in LPS-stimulated macrophages, even though trypsin-like proteasomal activity was reduced. These results demonstrate that the effects of H₂O₂ on NF-B and proteasomal activity are cell population specific.

reactive oxygen species; signal transduction; nuclear factor-B

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