| pubmed-article:21346252 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:21346252 | lifeskim:mentions | umls-concept:C0003968 | lld:lifeskim |
| pubmed-article:21346252 | lifeskim:mentions | umls-concept:C0030054 | lld:lifeskim |
| pubmed-article:21346252 | lifeskim:mentions | umls-concept:C1515655 | lld:lifeskim |
| pubmed-article:21346252 | pubmed:issue | 20 | lld:pubmed |
| pubmed-article:21346252 | pubmed:dateCreated | 2011-5-20 | lld:pubmed |
| pubmed-article:21346252 | pubmed:abstractText | Prolyl-4-hydroxylation is necessary for proper structural assembly of collagens and oxygen-dependent protein stability of hypoxia-inducible transcription factors (HIFs). In vitro function of HIF prolyl-4-hydroxylase domain (PHD) enzymes requires oxygen and 2-oxoglutarate as cosubstrates with iron(II) and vitamin C serving as cofactors. Although vitamin C deficiency is known to cause the collagen-disassembly disease scurvy, it is unclear whether cellular oxygen sensing is similarly affected. Here, we report that vitamin C-deprived Gulo(-/-) knockout mice show normal HIF-dependent gene expression. The systemic response of Gulo(-/-) animals to inspiratory hypoxia, as measured by plasma erythropoietin levels, was similar to that of animals supplemented with vitamin C. Hypoxic HIF induction was also essentially normal under serum- and vitamin C-free cell-culture conditions, suggesting that vitamin C is not required for oxygen sensing in vivo. Glutathione was found to fully substitute for vitamin C requirement of all 3 PHD isoforms in vitro. Consistently, glutathione also reduced HIF-1? protein levels, transactivation activity, and endogenous target gene expression in cells exposed to CoCl(2). A Cys201Ser mutation in PHD2 increased basal hydroxylation rates and conferred resistance to oxidative damage in vitro, suggesting that this surface-accessible PHD2 cysteine residue is a target of antioxidative protection by vitamin C and glutathione. | lld:pubmed |
| pubmed-article:21346252 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21346252 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21346252 | pubmed:language | eng | lld:pubmed |
| pubmed-article:21346252 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21346252 | pubmed:citationSubset | AIM | lld:pubmed |
| pubmed-article:21346252 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21346252 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21346252 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21346252 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21346252 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21346252 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21346252 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21346252 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21346252 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21346252 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21346252 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21346252 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:21346252 | pubmed:month | May | lld:pubmed |
| pubmed-article:21346252 | pubmed:issn | 1528-0020 | lld:pubmed |
| pubmed-article:21346252 | pubmed:author | pubmed-author:MaedaNobuyoN | lld:pubmed |
| pubmed-article:21346252 | pubmed:author | pubmed-author:WengerRoland... | lld:pubmed |
| pubmed-article:21346252 | pubmed:author | pubmed-author:StiehlDaniel... | lld:pubmed |
| pubmed-article:21346252 | pubmed:author | pubmed-author:SpielmannPatr... | lld:pubmed |
| pubmed-article:21346252 | pubmed:author | pubmed-author:NytkoKatarzyn... | lld:pubmed |
| pubmed-article:21346252 | pubmed:author | pubmed-author:SchläfliPhili... | lld:pubmed |
| pubmed-article:21346252 | pubmed:issnType | Electronic | lld:pubmed |
| pubmed-article:21346252 | pubmed:day | 19 | lld:pubmed |
| pubmed-article:21346252 | pubmed:volume | 117 | lld:pubmed |
| pubmed-article:21346252 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:21346252 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:21346252 | pubmed:pagination | 5485-93 | lld:pubmed |
| pubmed-article:21346252 | pubmed:meshHeading | pubmed-meshheading:21346252... | lld:pubmed |
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| pubmed-article:21346252 | pubmed:meshHeading | pubmed-meshheading:21346252... | lld:pubmed |
| pubmed-article:21346252 | pubmed:meshHeading | pubmed-meshheading:21346252... | lld:pubmed |
| pubmed-article:21346252 | pubmed:meshHeading | pubmed-meshheading:21346252... | lld:pubmed |
| pubmed-article:21346252 | pubmed:meshHeading | pubmed-meshheading:21346252... | lld:pubmed |
| pubmed-article:21346252 | pubmed:meshHeading | pubmed-meshheading:21346252... | lld:pubmed |
| pubmed-article:21346252 | pubmed:meshHeading | pubmed-meshheading:21346252... | lld:pubmed |
| pubmed-article:21346252 | pubmed:meshHeading | pubmed-meshheading:21346252... | lld:pubmed |
| pubmed-article:21346252 | pubmed:year | 2011 | lld:pubmed |
| pubmed-article:21346252 | pubmed:articleTitle | Vitamin C is dispensable for oxygen sensing in vivo. | lld:pubmed |
| pubmed-article:21346252 | pubmed:affiliation | Institute of Physiology and Zürich Center for Integrative Human Physiology, University of Zürich, Zürich, Switzerland. | lld:pubmed |
| pubmed-article:21346252 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:21346252 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
| pubmed-article:21346252 | pubmed:publicationType | Research Support, N.I.H., Extramural | lld:pubmed |
| entrez-gene:112405 | entrezgene:pubmed | pubmed-article:21346252 | lld:entrezgene |
| entrez-gene:268756 | entrezgene:pubmed | pubmed-article:21346252 | lld:entrezgene |
| http://linkedlifedata.com/r... | pubmed:referesTo | pubmed-article:21346252 | lld:pubmed |
