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Am J Physiol Cell Physiol (March 28, 2007). doi:10.1152/ajpcell.00618.2006
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Submitted on December 12, 2006
Accepted on March 22, 2007

Exposure to hydrogen peroxide diminishes NF-{kappa}B activation, I{kappa}B-{alpha} degradation, and proteasome activity in neutrophils

Jaroslaw Waldemar Zmijewski1, Xia Zhao1, Zhiwei Xu1, and Edward Abraham1*

1 Medicine, University of Alabama at Birmingham, Birmingham, Alabama, United States

* To whom correspondence should be addressed. E-mail: eabraham{at}uab.edu.

Although reactive oxygen species can participate in modulating the activity of the transcriptional factor NF-{kappa}B and expression of NF-{kappa}B dependent genes, the mechanisms involved and the roles of specific reactive oxygen species have not been fully determined. In particular, individual reactive oxygen species appear to have differing effects on NF-{kappa}B activation dependent on the cell population studied. In the present studies, we examined the ability of hydrogen peroxide (H2O2) to affect NF-{kappa}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-{kappa}B and decreased production of the NF-{kappa}B dependent cytokines, TNF-{alpha} and MIP-2. H2O2 treatment resulted in diminished trypsin- and chymotrypsin-like proteasome activity. The degradation of I{kappa}B-{alpha} 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-{kappa}B and proteasomal activity are cell population specific.




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