Linked Life Data

15292179

Source:http://linkedlifedata.com/resource/pubmed/id/15292179

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
40
pubmed:dateCreated
2004-9-27
pubmed:abstractText
Oxidative stress plays a major role in hyperoxia-induced acute lung injury. We have shown previously that mice lacking the Nrf2 are more susceptible to hyperoxia than are wild-type mice. Nrf2 activates antioxidant response element (ARE)-mediated gene expression involved in cellular protection against toxic insults. The present study was designed to investigate the mechanisms that control the activation of Nrf2 by hyperoxia using a non-malignant murine alveolar epithelial cell line, C10. No significant alteration in the levels of Nrf2 mRNA and protein was found following exposure to hyperoxia. In contrast, hyperoxia caused the translocation of Nrf2 from the cytoplasm to the nucleus within 30-60 min of exposure. Consistent with these observations, gel shift and reporter analyses demonstrated a correlation between the hyperoxia-enhanced ARE DNA-binding activity of Nrf2 and an up-regulation of ARE-driven transcription. Inhibition of NADPH oxidase with diphenyleneiodonium (DPI) blocked both Nrf2 translocation and ARE-mediated transcription. Inhibition of the MEK/ERK pathway caused a similar effect. Consistent with this finding, hyperoxia stimulated ERK-1 and ERK-2 phosphorylation, whereas DPI or N-acetyl-l-cysteine blocked such activation. Hyperoxia stimulated the phosphorylation of endogenous Nrf2, but not in the presence of U0126, suggesting a critical role for ERK signaling in the activation of Nrf2. Consistent with this notion, hyperoxia did not stimulate the phosphorylation of Nrf2 in fibroblasts lacking the ERK-1. Collectively, our findings suggest that hyperoxia-induced, ARE-driven, Nrf2-dependent transcription is controlled by NADPH oxidase and ERK-1 signaling.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
279
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
42302-12
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:15292179-Active Transport, Cell Nucleus, pubmed-meshheading:15292179-Animals, pubmed-meshheading:15292179-Cell Line, pubmed-meshheading:15292179-DNA-Binding Proteins, pubmed-meshheading:15292179-Epithelial Cells, pubmed-meshheading:15292179-Hyperoxia, pubmed-meshheading:15292179-Lung, pubmed-meshheading:15292179-MAP Kinase Signaling System, pubmed-meshheading:15292179-Mice, pubmed-meshheading:15292179-Mitogen-Activated Protein Kinase 3, pubmed-meshheading:15292179-Mitogen-Activated Protein Kinases, pubmed-meshheading:15292179-NADPH Oxidase, pubmed-meshheading:15292179-NF-E2-Related Factor 2, pubmed-meshheading:15292179-Phosphorylation, pubmed-meshheading:15292179-RNA, Messenger, pubmed-meshheading:15292179-Reactive Oxygen Species, pubmed-meshheading:15292179-Response Elements, pubmed-meshheading:15292179-Trans-Activators, pubmed-meshheading:15292179-Transcription, Genetic, pubmed-meshheading:15292179-Up-Regulation
pubmed:year
2004
pubmed:articleTitle
NADPH oxidase and ERK signaling regulates hyperoxia-induced Nrf2-ARE transcriptional response in pulmonary epithelial cells.
pubmed:affiliation
Department of Environmental Health Sciences, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.