Source:http://linkedlifedata.com/resource/pubmed/id/15941769
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
10
|
| pubmed:dateCreated |
2005-7-29
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| pubmed:abstractText |
Hypoxia-inducible transcription factor (HIF) is regulated by two oxygen-dependent events that are catalyzed by the HIF prolyl 4-hydroxylases (HIF-P4Hs) and HIF asparaginyl hydroxylase (FIH). We have purified the three recombinant human HIF-P4Hs to near homogeneity and characterized their catalytic properties and inhibition and those of FIH. The specific activities of the HIF-P4Hs were at least 40-50 mol/mol/min, and they and FIH catalyzed an uncoupled decarboxylation of 2-oxoglutarate in the absence of any peptide substrate. The purified HIF-P4Hs showed considerable activities even without added Fe2+, their apparent Km values for iron being markedly lower than that of FIH. Desferrioxamine and several metals were effective inhibitors of FIH, but surprisingly, ineffective inhibitors of the HIF-P4Hs in vitro, especially of HIF-P4H-2. Desferrioxamine and cobalt were more effective in cultured insect cells synthesizing recombinant HIF-P4H-2, but complete inhibition was not achieved and most of the enzyme was inactivated irreversibly. Cobalt also rapidly inactivated HIF-P4Hs during storage at 4 degrees C. The well-known stabilization of HIF-alpha by cobalt and nickel is thus not due to a simple competitive inhibition of HIF-P4Hs. The effective inhibition of FIH by these metals and zinc probably leads to full transcriptional activity of HIF-alpha even in concentrations that produce no stabilization of HIF-alpha.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Cobalt,
http://linkedlifedata.com/resource/pubmed/chemical/Deferoxamine,
http://linkedlifedata.com/resource/pubmed/chemical/HIF1A protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Hypoxia-Inducible Factor 1, alpha...,
http://linkedlifedata.com/resource/pubmed/chemical/Iron,
http://linkedlifedata.com/resource/pubmed/chemical/Metals,
http://linkedlifedata.com/resource/pubmed/chemical/Nickel,
http://linkedlifedata.com/resource/pubmed/chemical/Oxygen,
http://linkedlifedata.com/resource/pubmed/chemical/Procollagen-Proline Dioxygenase,
http://linkedlifedata.com/resource/pubmed/chemical/Serum Albumin, Bovine,
http://linkedlifedata.com/resource/pubmed/chemical/Vascular Endothelial Growth Factor A,
http://linkedlifedata.com/resource/pubmed/chemical/Zinc
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Aug
|
| pubmed:issn |
1530-6860
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| pubmed:author | |
| pubmed:issnType |
Electronic
|
| pubmed:volume |
19
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
1308-10
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| pubmed:dateRevised |
2006-11-15
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| pubmed:meshHeading |
pubmed-meshheading:15941769-Amino Acid Sequence,
pubmed-meshheading:15941769-Cell Line,
pubmed-meshheading:15941769-Cobalt,
pubmed-meshheading:15941769-Deferoxamine,
pubmed-meshheading:15941769-Humans,
pubmed-meshheading:15941769-Hypoxia-Inducible Factor 1, alpha Subunit,
pubmed-meshheading:15941769-Iron,
pubmed-meshheading:15941769-Metals,
pubmed-meshheading:15941769-Molecular Sequence Data,
pubmed-meshheading:15941769-Nickel,
pubmed-meshheading:15941769-Oxygen,
pubmed-meshheading:15941769-Procollagen-Proline Dioxygenase,
pubmed-meshheading:15941769-Serum Albumin, Bovine,
pubmed-meshheading:15941769-Vascular Endothelial Growth Factor A,
pubmed-meshheading:15941769-Zinc
|
| pubmed:year |
2005
|
| pubmed:articleTitle |
Effect of desferrioxamine and metals on the hydroxylases in the oxygen sensing pathway.
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| pubmed:affiliation |
Collagen Research Unit, Biocenter Oulu and Department of Medical Biochemistry and Molecular Biology, University of Oulu, Oulu, Finland.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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