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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
6
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pubmed:dateCreated |
2002-3-5
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pubmed:abstractText |
Plasminogen activator inhibitor-1 (PAI-1) plays a key role in control of coagulation and tissue remodeling and has been shown to be regulated by a number of cell stimuli, among those hypoxia. In this study we characterize the hypoxia-mediated induction of PAI-1 in human hepatoma cell line HepG2. We found that PAI-1 is tightly regulated in a narrow oxygen gradient. After incubation at oxygen concentrations of 1% to 2%, a 60-fold increase in PAI-1 messenger RNA levels was observed, whereas mild hypoxic conditions of more than 3.5% did not appear to induce transcription. Moreover, increased levels of PAI-1 protein were observed after incubation at low oxygen tensions. Through sequence analysis, several putative hypoxia-response elements (HREs 1-5) were identified in the human PAI-I promoter. Reporter gene assays showed that the HRE-2 (-194 to -187) was necessary and sufficient for the hypoxia-mediated response. By electrophoretic mobility assay we observed hypoxia-dependent binding of a protein complex to the HRE-2 motif. Further analysis demonstrated that HRE-2 was specifically recognized by the hypoxia-inducible transcription factor 1alpha-arylhydrocarbon nuclear translocator complex. Taken together, our data demonstrate that hypoxia-induced transcription is mediated through HIF-1 interaction with the HRE-2 site of the human PAI-1 promoter.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/ARNT protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Aryl Hydrocarbon Receptor Nuclear...,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/HIF1A protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Hypoxia-Inducible Factor 1,
http://linkedlifedata.com/resource/pubmed/chemical/Hypoxia-Inducible Factor 1, alpha...,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Oxygen,
http://linkedlifedata.com/resource/pubmed/chemical/Plasminogen Activator Inhibitor 1,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Aryl Hydrocarbon,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
0006-4971
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
99
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2077-83
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:11877282-Anoxia,
pubmed-meshheading:11877282-Aryl Hydrocarbon Receptor Nuclear Translocator,
pubmed-meshheading:11877282-Base Sequence,
pubmed-meshheading:11877282-DNA-Binding Proteins,
pubmed-meshheading:11877282-Dose-Response Relationship, Drug,
pubmed-meshheading:11877282-Gene Expression Regulation,
pubmed-meshheading:11877282-Humans,
pubmed-meshheading:11877282-Hypoxia-Inducible Factor 1,
pubmed-meshheading:11877282-Hypoxia-Inducible Factor 1, alpha Subunit,
pubmed-meshheading:11877282-Molecular Sequence Data,
pubmed-meshheading:11877282-Nuclear Proteins,
pubmed-meshheading:11877282-Oxygen,
pubmed-meshheading:11877282-Plasminogen Activator Inhibitor 1,
pubmed-meshheading:11877282-Promoter Regions, Genetic,
pubmed-meshheading:11877282-RNA, Messenger,
pubmed-meshheading:11877282-Receptors, Aryl Hydrocarbon,
pubmed-meshheading:11877282-Response Elements,
pubmed-meshheading:11877282-Sequence Alignment,
pubmed-meshheading:11877282-Transcription Factors,
pubmed-meshheading:11877282-Tumor Cells, Cultured
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pubmed:year |
2002
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pubmed:articleTitle |
Identification of a tightly regulated hypoxia-response element in the promoter of human plasminogen activator inhibitor-1.
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pubmed:affiliation |
Department of Virus and Cancer, Danish Cancer Society, Gustav Wieds Vej 10, 8000 Aarhus C, Denmark. trine@virus.au.dk
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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