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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1
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pubmed:dateCreated |
2000-12-4
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pubmed:abstractText |
Adaptation to hypoxic stress provokes activation of the hypoxia-inducible-factor-1 (HIF-1) which mediates gene expression of, e.g., erythropoietin or vascular endothelial growth factor. Detailed information on signaling pathways that stabilize HIF-1 is missing, but reactive oxygen species degrade the HIF-1 alpha subunit, whereas phosphorylation causes its stabilization. It was believed that hypoxia resembles the only HIF-1 inducer but recent evidence characterized other activators of HIF-1 such as nitric oxide (NO). Herein, we concentrated on NO-evoked HIF-1 induction as a heretofore unappreciated inflammatory response in association with massive NO formation. We demonstrated that S-nitrosoglutathione induces HIF-1 alpha accumulation and concomitant DNA binding. The response was attenuated by the kinase inhibitor genistein and blockers of phosphatidylinositol 3-kinase such as Ly 294002 or wortmannin. Whereas mitogen-activated protein kinases were not involved, we noticed phosphorylation/activation of Akt in correlation with HIF-1 alpha stabilization. NO appears to regulate HIF-1 alpha via the PI 3K/Akt pathway under normoxic conditions.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/2-(4-morpholinyl)-8-phenyl-4H-1-benz...,
http://linkedlifedata.com/resource/pubmed/chemical/Androstadienes,
http://linkedlifedata.com/resource/pubmed/chemical/Chromones,
http://linkedlifedata.com/resource/pubmed/chemical/DNA,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Genistein,
http://linkedlifedata.com/resource/pubmed/chemical/Glutathione,
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/Morpholines,
http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide,
http://linkedlifedata.com/resource/pubmed/chemical/Nitroso Compounds,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphodiesterase Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-akt,
http://linkedlifedata.com/resource/pubmed/chemical/S-Nitrosoglutathione,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/wortmannin
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
0006-291X
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pubmed:author |
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pubmed:copyrightInfo |
Copyright 2000 Academic Press.
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pubmed:issnType |
Print
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pubmed:day |
11
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pubmed:volume |
278
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
263-7
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:11071882-Androstadienes,
pubmed-meshheading:11071882-Animals,
pubmed-meshheading:11071882-Anoxia,
pubmed-meshheading:11071882-Blotting, Western,
pubmed-meshheading:11071882-Cell Line,
pubmed-meshheading:11071882-Cell Nucleus,
pubmed-meshheading:11071882-Chromones,
pubmed-meshheading:11071882-DNA,
pubmed-meshheading:11071882-DNA-Binding Proteins,
pubmed-meshheading:11071882-Enzyme Activation,
pubmed-meshheading:11071882-Enzyme Inhibitors,
pubmed-meshheading:11071882-Genistein,
pubmed-meshheading:11071882-Glutathione,
pubmed-meshheading:11071882-Hypoxia-Inducible Factor 1,
pubmed-meshheading:11071882-Hypoxia-Inducible Factor 1, alpha Subunit,
pubmed-meshheading:11071882-Inflammation,
pubmed-meshheading:11071882-MAP Kinase Signaling System,
pubmed-meshheading:11071882-Morpholines,
pubmed-meshheading:11071882-Nitric Oxide,
pubmed-meshheading:11071882-Nitroso Compounds,
pubmed-meshheading:11071882-Nuclear Proteins,
pubmed-meshheading:11071882-Phosphatidylinositol 3-Kinases,
pubmed-meshheading:11071882-Phosphodiesterase Inhibitors,
pubmed-meshheading:11071882-Phosphorylation,
pubmed-meshheading:11071882-Protein-Serine-Threonine Kinases,
pubmed-meshheading:11071882-Proto-Oncogene Proteins,
pubmed-meshheading:11071882-Proto-Oncogene Proteins c-akt,
pubmed-meshheading:11071882-S-Nitrosoglutathione,
pubmed-meshheading:11071882-Signal Transduction,
pubmed-meshheading:11071882-Swine,
pubmed-meshheading:11071882-Time Factors,
pubmed-meshheading:11071882-Transcription Factors
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pubmed:year |
2000
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pubmed:articleTitle |
Induction of hypoxia-inducible-factor 1 by nitric oxide is mediated via the PI 3K pathway.
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pubmed:affiliation |
Faculty of Medicine, Department of Medicine IV, University of Erlangen-Nürnberg, D-91054 Erlangen, Germany.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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