Linked Life Data

7929072

Source:http://linkedlifedata.com/resource/pubmed/id/7929072

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
39
pubmed:dateCreated
1994-10-27
pubmed:abstractText
Endothelial cell-derived oxygen free radicals are important mediators of postischemic injury; however, the mechanisms that trigger this radical generation are not known, and it is not known if this process can occur in human cells and tissues. The enzyme xanthine oxidase can be an important source of radical generation; however, it has been reported that this enzyme may not be present in human endothelium. To determine the presence and mechanisms of radical generation in human vascular endothelial cells subjected to anoxia and reoxygenation, electron paramagnetic resonance measurements were performed on cultured human aortic endothelial cells using the spin trap 5,5-dimethyl-1-pyrroline N-oxide (DMPO). These measurements were correlated with cellular injury, xanthine oxidase activity, and alterations in cellular nucleotides. Upon reoxygenation after 60 min of anoxia, large DMPO-OH (aN = aH = 14.9 G) and smaller DMPO-R (aN = 15.8 G, aH = 22.8 G) signals were seen. Superoxide dismutase totally quenched this radical generation. The ferric iron chelator deferoxamine prevented cell death and totally quenched the DMPO-R signal with a 40% decrease in the DMPO-OH signal. Xanthine oxidase was shown to be present in these cells and to be the primary source of free radicals. While the concentration of this enzyme did not change after anoxia, the concentration of its substrate, hypoxanthine, markedly increased, resulting in increased free radical generation upon reoxygenation. Thus, reoxygenated human vascular endothelial cells generate superoxide free radicals, which further react with iron to form the reactive hydroxyl radical, which in turn causes cell death. Xanthine oxidase was the primary source of radical generation with this process triggered by the breakdown of ATP to the substrate hypoxanthine during anoxia.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
30
pubmed:volume
269
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
24156-62
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
1994
pubmed:articleTitle
Determination of the mechanism of free radical generation in human aortic endothelial cells exposed to anoxia and reoxygenation.
pubmed:affiliation
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21224.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't