Source:http://linkedlifedata.com/resource/pubmed/id/14680803
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
3
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pubmed:dateCreated |
2003-12-18
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pubmed:abstractText |
Transcription factor HIF-1 is a key determinant of oxygen-dependent gene regulation. Suppression of HIF-1alpha is important for exploring HIF-1-dependent processes and for interfering with hypoxia-induced pathophysiological events. This study applied RNA-interference targeting HIF-1alpha to the human lung A549 cell line. Transfection of HIF-1alpha-siRNA reduced HIF-1alpha synthesis as measured on mRNA and protein level by realtime RT-PCR, Western blot, and immuncytochemistry. A time kinetic for hypoxic stabilization of HIF-1alpha protein and its inhibition by HIF-1alpha-siRNA is included. Hypoxic induction of HIF-1-controlled target genes as heme oxygenase I (HO-1), phosphoglycerate kinase (PGK), and vascular endothelial growth factor (VEGF) was markedly attenuated by HIF-1alpha-siRNA treatment. Correspondingly, gene activation via hypoxia-responsive-element, as shown by reporter gene assay, was inhibited by HIF-1alpha-siRNA. Moreover, this approach was found to suppress the shift from from S-phase to G1-phase observed in A549 cells in response to hypoxia, supporting a role of HIF-1alpha in oxygen-dependent cell cycle regulation.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
0006-291X
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
19
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pubmed:volume |
312
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
571-7
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:14680803-Anoxia,
pubmed-meshheading:14680803-Cell Division,
pubmed-meshheading:14680803-Cell Line,
pubmed-meshheading:14680803-Down-Regulation,
pubmed-meshheading:14680803-Humans,
pubmed-meshheading:14680803-Hypoxia-Inducible Factor 1, alpha Subunit,
pubmed-meshheading:14680803-RNA Interference,
pubmed-meshheading:14680803-Respiratory Mucosa,
pubmed-meshheading:14680803-Signal Transduction,
pubmed-meshheading:14680803-Transcription Factors
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pubmed:year |
2003
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pubmed:articleTitle |
RNA interference for HIF-1alpha inhibits its downstream signalling and affects cellular proliferation.
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pubmed:affiliation |
Department of Internal Medicine 2, Klinikstr. 36, Medical School of the Justus-Liebig-University, Giessen D-35392, Germany. joerg.haenze@innere.med.uni-giessen.de
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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