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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2000-8-14
pubmed:abstractText
Activation of nuclear factor (NF)-kappaB and subsequent proinflammatory gene expression in human airway epithelial cells can be evoked by oxidative stress. In this study we examined signal transduction pathways activated by vanadyl sulfate (V(IV))-induced oxidative stress in normal human bronchial epithelial cells. Both nuclear translocation of NF-kappaB and enhanced kappaB-dependent transcription induced by V(IV) were inhibited by overexpression of catalase, but not Cu,Zn superoxide dismutase (Cu,Zn-SOD), indicating that peroxides rather than superoxides initiated signaling. Catalase selectively blocked the response to V(IV) because it inhibited neither NF-kappaB translocation nor kappaB-dependent transcription evoked by the proinflammatory cytokine tumor necrosis factor (TNF)-alpha. The V(IV)-induced kappaB-dependent transcription was dependent upon activation of the p38 mitogen-activated protein kinase because overexpression of dominant-negative mutants of the p38 MAPK pathway inhibited V(IV)-induced kappaB-dependent transcription. This inhibition was not due to suppression of NF-kappaB nuclear translocation because NF-kappaB DNA binding was unaffected by the inhibition of p38 activity. Overexpression of catalase, but not Cu,Zn-SOD, inhibited p38 activation, indicating that peroxides activated p38. Catalase failed to block V(IV)- induced increases in phosphotyrosine levels, suggesting that the catalase-sensitive signaling components were independent of V(IV)-induced tyrosine phosphorylation. The data demonstrate that V(IV)-induced oxidative stress activates at least two distinct pathways, NF-kappaB nuclear translocation and p38-dependent transactivation of NF-kappaB, both of which are required to fully activate kappaB-dependent transcription. Moreover, V(IV)-induced oxidative stress activated these pathways in bronchial epithelial cells by upstream signaling cascades that were distinct at some level from those used by the proinflammatory cytokine TNF-alpha.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1044-1549
pubmed:author
pubmed:issnType
Print
pubmed:volume
23
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
95-102
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:10873158-Bronchi, pubmed-meshheading:10873158-Catalase, pubmed-meshheading:10873158-Cell Line, pubmed-meshheading:10873158-Cells, Cultured, pubmed-meshheading:10873158-Enzyme Activation, pubmed-meshheading:10873158-Epithelial Cells, pubmed-meshheading:10873158-Genes, Reporter, pubmed-meshheading:10873158-Humans, pubmed-meshheading:10873158-MAP Kinase Signaling System, pubmed-meshheading:10873158-Mitogen-Activated Protein Kinases, pubmed-meshheading:10873158-Mutation, pubmed-meshheading:10873158-NF-kappa B, pubmed-meshheading:10873158-Oxidative Stress, pubmed-meshheading:10873158-Peroxides, pubmed-meshheading:10873158-Phosphorylation, pubmed-meshheading:10873158-Phosphotyrosine, pubmed-meshheading:10873158-Reactive Oxygen Species, pubmed-meshheading:10873158-Superoxide Dismutase, pubmed-meshheading:10873158-Transcription, Genetic, pubmed-meshheading:10873158-Transcriptional Activation, pubmed-meshheading:10873158-Transfection, pubmed-meshheading:10873158-Tumor Necrosis Factor-alpha, pubmed-meshheading:10873158-Vanadium Compounds, pubmed-meshheading:10873158-p38 Mitogen-Activated Protein Kinases
pubmed:year
2000
pubmed:articleTitle
Vanadium-induced kappaB-dependent transcription depends upon peroxide-induced activation of the p38 mitogen-activated protein kinase.
pubmed:affiliation
Center for Environmental Medicine and Lung Biology, University of North Carolina School of Medicine, Chapel Hill, USA. Ilona_Jaspers@med.unc.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S.