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rdf:type |
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lifeskim:mentions |
umls-concept:C0028128,
umls-concept:C0037083,
umls-concept:C0044602,
umls-concept:C0205263,
umls-concept:C0215848,
umls-concept:C0752312,
umls-concept:C0851827,
umls-concept:C1370600,
umls-concept:C1701901,
umls-concept:C1710082,
umls-concept:C1879547
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pubmed:issue |
4
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pubmed:dateCreated |
2004-1-19
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pubmed:abstractText |
Hypoxia-inducible factor-1 (HIF-1) is a master regulator of cellular adaptive responses to hypoxia. Levels of the HIF-1alpha subunit increase under hypoxic conditions. Exposure of cells to certain nitric oxide (NO) donors also induces HIF-1alpha expression under nonhypoxic conditions. We demonstrate that exposure of cells to the NO donor NOC18 or S-nitrosoglutathione induces HIF-1alpha expression and transcriptional activity. In contrast to hypoxia, NOC18 did not inhibit HIF-1alpha hydroxylation, ubiquitination, and degradation, indicating an effect on HIF-1alpha protein synthesis that was confirmed by pulse labeling studies. NOC18 stimulation of HIF-1alpha protein and HIF-1-dependent gene expression was blocked by treating cells with an inhibitor of the phosphatidylinositol 3-kinase or MAPK-signaling pathway. These inhibitors also blocked NOC18-induced phosphorylation of the translational regulatory proteins 4E-BP1, p70 S6 kinase, and eIF-4E, thus providing a mechanism for the modulation of HIF-1alpha protein synthesis. In addition, expression of a dominant-negative form of Ras significantly suppressed HIF-1 activation by NOC18. We conclude that the NO donor NOC18 induces HIF-1alpha synthesis under conditions of NO formation during normoxia and that hydroxylation of HIF-1alpha is not regulated by NOC18.
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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/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/NOC 18,
http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide,
http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide Donors,
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/S-Nitrosoglutathione,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
23
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pubmed:volume |
279
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2550-8
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:14600153-Cell Line,
pubmed-meshheading:14600153-DNA-Binding Proteins,
pubmed-meshheading:14600153-Humans,
pubmed-meshheading:14600153-Hypoxia-Inducible Factor 1,
pubmed-meshheading:14600153-Hypoxia-Inducible Factor 1, alpha Subunit,
pubmed-meshheading:14600153-MAP Kinase Signaling System,
pubmed-meshheading:14600153-Nitric Oxide,
pubmed-meshheading:14600153-Nitric Oxide Donors,
pubmed-meshheading:14600153-Nitroso Compounds,
pubmed-meshheading:14600153-Nuclear Proteins,
pubmed-meshheading:14600153-Phosphatidylinositol 3-Kinases,
pubmed-meshheading:14600153-S-Nitrosoglutathione,
pubmed-meshheading:14600153-Transcription Factors
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pubmed:year |
2004
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pubmed:articleTitle |
Nitric oxide induces hypoxia-inducible factor 1 activation that is dependent on MAPK and phosphatidylinositol 3-kinase signaling.
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pubmed:affiliation |
Human Stress Signal Research Center, National Institute of Advanced Industrial Science and Technology, IKEDA, Osaka, Japan 563-0053.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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