title: Exposure to hydrogen peroxide diminishes NF-kappaB activation, IkappaB-alpha degradation, and proteasome activity in neutrophils.
abstract: Although ROS can participate in modulating the activity of the transcriptional factor NF-kappaB and expression of NF-kappaB-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-kappaB activation dependent on the cell population studied. In the present study, we examined the ability of H(2)O(2) to affect NF-kappaB activation in LPS-stimulated murine neutrophils and macrophages. Exposure of bone marrow or peritoneal neutrophils to H(2)O(2) was associated with reduced nuclear translocation of NF-kappaB and decreased production of the NF-kappaB-dependent cytokines TNF-alpha and macrophage inhibitory protein-2. H(2)O(2) treatment resulted in diminished trypsin- and chymotrypsin-like proteasome activity. The degradation of IkappaB-alpha normally found in LPS-treated neutrophils was prevented when H(2)O(2) was added to cell cultures. In contrast to the effects found in neutrophils, H(2)O(2) 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 H(2)O(2) on NF-kappaB and proteasomal activity are cell population specific.
authors: Dept. of Medicine, School of Medicine, University of Alabama, BDB 420, 1530 3rd Ave. S, Birmingham, AL 35294-0012, USA.
authors: Jaroslaw W
authors: JW
authors: Zmijewski
authors: Xia
authors: X
authors: Zhao
authors: Zhiwei
authors: Z
authors: Xu
authors: Edward
authors: E
authors: Abraham
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D054426:Chemokine CXCL2; D018925:Chemokines / Q000378:metabolism; D002918:Chymotrypsin / Q000037:antagonists & inhibitors / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006861:Hydrogen Peroxide / Q000378:metabolism* / Q000494:pharmacology; D020672:I-kappa B Proteins / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D009504:Neutrophils / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D015842:Serine Proteinase Inhibitors / Q000378:metabolism* / Q000494:pharmacology; D013997:Time Factors; D014357:Trypsin / Q000378:metabolism; D014361:Trypsin Inhibitors / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D054426:Chemokine CXCL2; D018925:Chemokines; C404915:Cxcl2 protein, mouse; D020672:I-kappa B Proteins; D008070:Lipopolysaccharides; D016328:NF-kappa B; C000606205:Nfkbia protein, mouse; D015842:Serine Proteinase Inhibitors; D014361:Trypsin Inhibitors; D014409:Tumor Necrosis Factor-alpha; C440499:lipopolysaccharide, Escherichia coli O111 B4; D000072000:NF-KappaB Inhibitor alpha; D006861:Hydrogen Peroxide; D002918:Chymotrypsin; D014357:Trypsin; D046988:Proteasome Endopeptidase Complex