Linked Life Data

21346252

Source:http://linkedlifedata.com/resource/pubmed/id/21346252

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
20
pubmed:dateCreated
2011-5-20
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.
pubmed:grant
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1528-0020
pubmed:author
pubmed:issnType
Electronic
pubmed:day
19
pubmed:volume
117
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5485-93
pubmed:meshHeading
pubmed-meshheading:21346252-Amino Acid Substitution, pubmed-meshheading:21346252-Animals, pubmed-meshheading:21346252-Ascorbic Acid, pubmed-meshheading:21346252-Ascorbic Acid Deficiency, pubmed-meshheading:21346252-Cell Hypoxia, pubmed-meshheading:21346252-Cell Line, pubmed-meshheading:21346252-Cobalt, pubmed-meshheading:21346252-Glutathione, pubmed-meshheading:21346252-HeLa Cells, pubmed-meshheading:21346252-Humans, pubmed-meshheading:21346252-Hypoxia-Inducible Factor 1, alpha Subunit, pubmed-meshheading:21346252-L-Gulonolactone Oxidase, pubmed-meshheading:21346252-Mice, pubmed-meshheading:21346252-Mice, Knockout, pubmed-meshheading:21346252-Mutagenesis, Site-Directed, pubmed-meshheading:21346252-Mutant Proteins, pubmed-meshheading:21346252-Oxygen, pubmed-meshheading:21346252-Procollagen-Proline Dioxygenase
pubmed:year
2011
pubmed:articleTitle
Vitamin C is dispensable for oxygen sensing in vivo.
pubmed:affiliation
Institute of Physiology and Zürich Center for Integrative Human Physiology, University of Zürich, Zürich, Switzerland.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural