Source:http://linkedlifedata.com/resource/pubmed/id/18073334
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
5
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pubmed:dateCreated |
2008-5-2
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pubmed:abstractText |
Hypoxia inhibits Na-K-ATPase activity and leads to its degradation in mammalian cells. Von Hippel Lindau protein (pVHL) and hypoxia inducible factor (HIF) are key mediators in cellular adaptation to hypoxia; thus, we set out to investigate whether pVHL and HIF participate in the hypoxia-mediated degradation of plasma membrane Na-K-ATPase. We found that in the presence of pVHL hypoxia decreased Na-K-ATPase activity and promoted the degradation of plasma membrane Na-K-ATPase. In pVHL-deficient cells, hypoxia did not decrease the Na-K-ATPase activity and the degradation of plasma membrane Na-K-ATPase was prevented. pVHL-mediated degradation of Na-K-ATPase required the functional pVHL E3 ligase and Ubc5 since pVHL mutants and dominant-negative Ubc5 prevented Na-K-ATPase from degradation. The generation of reactive oxygen species was necessary for pVHL-mediated Na-K-ATPase degradation during hypoxia. Desferrioxamine, which stabilizes HIF1/2alpha, did not affect the half-life of plasma membrane Na-K-ATPase. In addition, stabilizing HIF1/2alpha by infecting mammalian cells with adenoviruses containing the oxygen-dependent degradation domain of HIF1alpha did not affect the plasma membrane Na-K-ATPase degradation. In cells with suppression of pVHL by short hairpin RNA, the Na-K-ATPase was not degraded during hypoxia, whereas cells with knockdown of HIF1/2alpha retained the ability to degrade plasma membrane Na-K-ATPase. These findings suggest that pVHL participates in the hypoxia-mediated degradation of plasma membrane Na-K-ATPase in a HIF-independent manner.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Basic Helix-Loop-Helix...,
http://linkedlifedata.com/resource/pubmed/chemical/Deferoxamine,
http://linkedlifedata.com/resource/pubmed/chemical/EUK-134,
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/Organometallic Compounds,
http://linkedlifedata.com/resource/pubmed/chemical/Salicylates,
http://linkedlifedata.com/resource/pubmed/chemical/Sodium-Potassium-Exchanging ATPase,
http://linkedlifedata.com/resource/pubmed/chemical/Von Hippel-Lindau Tumor Suppressor...,
http://linkedlifedata.com/resource/pubmed/chemical/endothelial PAS domain-containing...
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
1530-6860
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pubmed:author | |
pubmed:issnType |
Electronic
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pubmed:volume |
22
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1335-42
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pubmed:meshHeading |
pubmed-meshheading:18073334-Animals,
pubmed-meshheading:18073334-Anoxia,
pubmed-meshheading:18073334-Basic Helix-Loop-Helix Transcription Factors,
pubmed-meshheading:18073334-COS Cells,
pubmed-meshheading:18073334-Cell Membrane,
pubmed-meshheading:18073334-Cells, Cultured,
pubmed-meshheading:18073334-Cercopithecus aethiops,
pubmed-meshheading:18073334-Deferoxamine,
pubmed-meshheading:18073334-Humans,
pubmed-meshheading:18073334-Hypoxia-Inducible Factor 1, alpha Subunit,
pubmed-meshheading:18073334-Organometallic Compounds,
pubmed-meshheading:18073334-Salicylates,
pubmed-meshheading:18073334-Sodium-Potassium-Exchanging ATPase,
pubmed-meshheading:18073334-Von Hippel-Lindau Tumor Suppressor Protein
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pubmed:year |
2008
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pubmed:articleTitle |
Hypoxia-mediated Na-K-ATPase degradation requires von Hippel Lindau protein.
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pubmed:affiliation |
Pulmonary and Critical Care Medicine, Feinberg School of Medicine, Northwestern University, 240 E. Huron, Chicago, IL 60611, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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