Linked Life Data

8663020

Source:http://linkedlifedata.com/resource/pubmed/id/8663020

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
25
pubmed:dateCreated
1996-8-13
pubmed:abstractText
Cultured vascular smooth muscle cells (SMC) and endothelial cells (EC) stimulate low density lipoprotein (LDL) oxidation by free radical-mediated, transition metal-dependent mechanisms. The physiological source(s) of metal ions is not known; however, purified ceruloplasmin, a plasma protein containing 7 coppers, oxidizes LDL in vitro. We now show that ceruloplasmin also increases LDL oxidation by vascular cells. In metal ion-free medium, human ceruloplasmin increased bovine aortic SMC- and EC-mediated LDL oxidation by up to 30- and 15-fold, respectively. The maximal response was at 100-300 microg ceruloplasmin/ml, a level at or below the unevoked physiological plasma concentration. Oxidant activity was dependent on protein structure as a specific proteolytic cleavage or removal of one of the seven ceruloplasmin copper atoms inhibited activity. Three lines of evidence indicated a critical role for cellular superoxide (O2.) in ceruloplasmin-stimulated oxidation. First, the rate of production of O2. by cells correlated with their rates of LDL oxidation. Second, superoxide dismutase effectively blocked ceruloplasmin-stimulated oxidation by both cell types. Finally, O2. production by SMC quantitatively accounted for the observed rate of LDL oxidation. To show this, the course of O2. production by SMC was simulated by repeated addition of xanthine and xanthine oxidase to culture medium under cell-free conditions. Neither ceruloplasmin nor O2. alone increased LDL oxidation, but together they completely reconstituted the oxidation rate of ceruloplasmin-stimulated SMC. These results are the first to show that ceruloplasmin stimulates EC- and SMC-mediated oxidation of LDL and that cell-derived O2. accounts quantitatively for metal-dependent, free radical-initiated oxidation of LDL by these cells.
pubmed:grant
pubmed:keyword
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
21
pubmed:volume
271
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
14773-8
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:8663020-Animals, pubmed-meshheading:8663020-Aorta, pubmed-meshheading:8663020-Catalase, pubmed-meshheading:8663020-Cattle, pubmed-meshheading:8663020-Cells, Cultured, pubmed-meshheading:8663020-Ceruloplasmin, pubmed-meshheading:8663020-Dose-Response Relationship, Drug, pubmed-meshheading:8663020-Endothelium, Vascular, pubmed-meshheading:8663020-Formic Acids, pubmed-meshheading:8663020-Free Radical Scavengers, pubmed-meshheading:8663020-Glutathione, pubmed-meshheading:8663020-Humans, pubmed-meshheading:8663020-Kinetics, pubmed-meshheading:8663020-Lipoproteins, LDL, pubmed-meshheading:8663020-Mannitol, pubmed-meshheading:8663020-Muscle, Smooth, Vascular, pubmed-meshheading:8663020-Oxidation-Reduction, pubmed-meshheading:8663020-Superoxide Dismutase, pubmed-meshheading:8663020-Superoxides, pubmed-meshheading:8663020-Thiourea
pubmed:year
1996
pubmed:articleTitle
Ceruloplasmin enhances smooth muscle cell- and endothelial cell-mediated low density lipoprotein oxidation by a superoxide-dependent mechanism.
pubmed:affiliation
Department of Cell Biology, Cleveland Clinic Research Institute, Cleveland, Ohio 44195, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't